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Zheng J, Chen R, Hao J, Yang Y, Xu S, Zhang F, Zhang F, Yao Y. Design and preparation of hydrogel microspheres for spinal cord injury repair. J Biomed Mater Res A 2024; 112:2358-2371. [PMID: 39169748 DOI: 10.1002/jbm.a.37788] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/01/2024] [Revised: 07/24/2024] [Accepted: 08/10/2024] [Indexed: 08/23/2024]
Abstract
A severe disorder known as spinal cord damage causes both motor and sensory impairment in the limbs, significantly reducing the patients' quality of life. After a spinal cord injury, functional recovery and therapy have emerged as critical concerns. Hydrogel microspheres have garnered a lot of interest lately because of their enormous promise in the field of spinal cord injury rehabilitation. The material classification of hydrogel microspheres (natural and synthetic macromolecule polymers) and their synthesis methods are examined in this work. This work also covers the introduction of several kinds of hydrogel microspheres and their use as carriers in the realm of treating spinal cord injuries. Lastly, the study reviews the future prospects for hydrogel microspheres and highlights their limitations and problems. This paper can offer feasible ideas for researchers to advance the application of hydrogel microspheres in the field of spinal cord injury.
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Affiliation(s)
- Jian Zheng
- Medical School of Nantong University, Nantong, Jiangsu Province, China
- Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Ruilin Chen
- Medical School of Nantong University, Nantong, Jiangsu Province, China
- Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Jie Hao
- Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Yang Yang
- Department of Emergency Surgery, Affiliated Hospital of Nantong University, Nantong, Jiangsu, China
| | - Shaohu Xu
- Medical School of Nantong University, Nantong, Jiangsu Province, China
- Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Feiyu Zhang
- Medical School of Nantong University, Nantong, Jiangsu Province, China
- Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Feng Zhang
- Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
| | - Yu Yao
- Department of Orthopedics, Affiliated Hospital of Nantong University, Nantong, Jiangsu Province, China
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Soleymani H, Ghorbani M, Sedghi M, Allahverdi A, Naderi-Manesh H. Microfluidics single-cell encapsulation reveals that poly-l-lysine-mediated stem cell adhesion to alginate microgels is crucial for cell-cell crosstalk and its self-renewal. Int J Biol Macromol 2024; 274:133418. [PMID: 38936577 DOI: 10.1016/j.ijbiomac.2024.133418] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/12/2023] [Revised: 04/08/2024] [Accepted: 06/23/2024] [Indexed: 06/29/2024]
Abstract
Microfluidic cell encapsulation has provided a platform for studying the behavior of individual cells and has become a turning point in single-cell analysis during the last decade. The engineered microenvironment, along with protecting the immune response, has led to increasingly presenting the results of practical and pre-clinical studies with the goals of disease treatment, tissue engineering, intelligent control of stem cell differentiation, and regenerative medicine. However, the significance of cell-substrate interaction versus cell-cell communications in the microgel is still unclear. In this study, monodisperse alginate microgels were generated using a flow-focusing microfluidic device to determine how the cell microenvironment can control human bone marrow-derived mesenchymal stem cells (hBMSCs) viability, proliferation, and biomechanical features in single-cell droplets versus multi-cell droplets. Collected results show insufficient cell proliferation (234 % and 329 %) in both single- and multi-cell alginate microgels. Alginate hydrogels supplemented with poly-l-lysine (PLL) showed a better proliferation rate (514 % and 780 %) in a comparison of free alginate hydrogels. Cell stiffness data illustrate that hBMSCs cultured in alginate hydrogels have higher membrane flexibility and migration potency (Young's modulus equal to 1.06 kPa), whereas PLL introduces more binding sites for cell attachment and causes lower flexibility and migration potency (Young's modulus equal to 1.83 kPa). Considering that cell adhesion is the most important parameter in tissue engineering, in which cells do not run away from a 3D substrate, PLL enhances cell stiffness and guarantees cell attachments. In conclusion, cell attachment to PLL-mediated alginate hydrogels is crucial for cell viability and proliferation. It suggests that cell-cell signaling is good enough for stem cell viability, but cell-PLL attachment alongside cell-cell signaling is crucial for stem cell proliferation and self-renewal.
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Affiliation(s)
- Hossein Soleymani
- Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154 Tehran, Iran.
| | - Mohammad Ghorbani
- Faculty of Natural Sciences, University of Tabriz, 51666-16471 Tabriz, Iran
| | - Mosslim Sedghi
- Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154 Tehran, Iran
| | - Abdollah Allahverdi
- Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154 Tehran, Iran.
| | - Hossein Naderi-Manesh
- Biophysics Department, Faculty of Biological Sciences, Tarbiat Modares University, 14115-154 Tehran, Iran; Department of Nanobiotechnology, Faculty of Biological Science, Tarbiat Modares University, 14115-154 Tehran, Iran.
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Zhu Y, Gu H, Yang J, Li A, Hou L, Zhou M, Jiang X. An Injectable silk-based hydrogel as a novel biomineralization seedbed for critical-sized bone defect regeneration. Bioact Mater 2024; 35:274-290. [PMID: 38370865 PMCID: PMC10873665 DOI: 10.1016/j.bioactmat.2024.01.024] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/10/2023] [Revised: 01/10/2024] [Accepted: 01/25/2024] [Indexed: 02/20/2024] Open
Abstract
The healing process of critical-sized bone defects urges for a suitable biomineralization environment. However, the unsatisfying repair outcome usually results from a disturbed intricate milieu and the lack of in situ mineralization resources. In this work, we have developed a composite hydrogel that mimics the natural bone healing processes and serves as a seedbed for bone regeneration. The oxidized silk fibroin and fibrin are incorporated as rigid geogrids, and amorphous calcium phosphate (ACP) and platelet-rich plasma serve as the fertilizers and loam, respectively. Encouragingly, the seedbed hydrogel demonstrates excellent mechanical and biomineralization properties as a stable scaffold and promotes vascularized bone regeneration in vivo. Additionally, the seedbed serves a succinate-like function via the PI3K-Akt signaling pathway and subsequently orchestrates the mitochondrial calcium uptake, further converting the exogenous ACP into endogenous ACP. Additionally, the seedbed hydrogel realizes the succession of calcium resources and promotes the evolution of the biotemplate from fibrin to collagen. Therefore, our work has established a novel silk-based hydrogel that functions as an in-situ biomineralization seedbed, providing a new insight for critical-sized bone defect regeneration.
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Affiliation(s)
- Yuhui Zhu
- Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, No. 115 Jinzun Road, Shanghai, 200125, China
- National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 115 Jinzun Road, Shanghai 200125, China
| | - Hao Gu
- Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, No. 115 Jinzun Road, Shanghai, 200125, China
- National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 115 Jinzun Road, Shanghai 200125, China
| | - Jiawei Yang
- Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, No. 115 Jinzun Road, Shanghai, 200125, China
- National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 115 Jinzun Road, Shanghai 200125, China
| | - Anshuo Li
- Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, No. 115 Jinzun Road, Shanghai, 200125, China
- National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 115 Jinzun Road, Shanghai 200125, China
| | - Lingli Hou
- Shanghai Institute of Precision Medicine, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 115 Jinzun Road, Shanghai, 200125, China
| | - Mingliang Zhou
- Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, No. 115 Jinzun Road, Shanghai, 200125, China
- National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 115 Jinzun Road, Shanghai 200125, China
| | - Xinquan Jiang
- Department of Prosthodontics, Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine, No. 639 Zhizaoju Road, Shanghai, 200011, China
- College of Stomatology, Shanghai Jiao Tong University, No. 115 Jinzun Road, Shanghai, 200125, China
- National Center for Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- National Clinical Research Center for Oral Diseases, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Key Laboratory of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Research Institute of Stomatology, No. 639 Zhizaoju Road, Shanghai, 200011, China
- Shanghai Engineering Research Center of Advanced Dental Technology and Materials, No. 115 Jinzun Road, Shanghai 200125, China
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Romano IR, D'Angeli F, Vicario N, Russo C, Genovese C, Lo Furno D, Mannino G, Tamburino S, Parenti R, Giuffrida R. Adipose-Derived Mesenchymal Stromal Cells: A Tool for Bone and Cartilage Repair. Biomedicines 2023; 11:1781. [PMID: 37509421 PMCID: PMC10376676 DOI: 10.3390/biomedicines11071781] [Citation(s) in RCA: 7] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/24/2023] [Revised: 06/16/2023] [Accepted: 06/20/2023] [Indexed: 07/30/2023] Open
Abstract
The osteogenic and chondrogenic differentiation ability of adipose-derived mesenchymal stromal cells (ASCs) and their potential therapeutic applications in bone and cartilage defects are reported in this review. This becomes particularly important when these disorders can only be poorly treated by conventional therapeutic approaches, and tissue engineering may represent a valuable alternative. Being of mesodermal origin, ASCs can be easily induced to differentiate into chondrocyte-like and osteocyte-like elements and used to repair damaged tissues. Moreover, they can be easily harvested and used for autologous implantation. A plethora of ASC-based strategies are being developed worldwide: they include the transplantation of freshly harvested cells, in vitro expanded cells or predifferentiated cells. Moreover, improving their positive effects, ASCs can be implanted in combination with several types of scaffolds that ensure the correct cell positioning; support cell viability, proliferation and migration; and may contribute to their osteogenic or chondrogenic differentiation. Examples of these strategies are described here, showing the enormous therapeutic potential of ASCs in this field. For safety and regulatory issues, most investigations are still at the experimental stage and carried out in vitro and in animal models. Clinical applications have, however, been reported with promising results and no serious adverse effects.
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Affiliation(s)
- Ivana Roberta Romano
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Floriana D'Angeli
- Department of Human Sciences and Quality of Life Promotion, San Raffaele Roma Open University, 00166 Rome, Italy
| | - Nunzio Vicario
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Cristina Russo
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Carlo Genovese
- Faculty of Medicine and Surgery, "Kore" University of Enna, 94100 Enna, Italy
| | - Debora Lo Furno
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Giuliana Mannino
- Department of Chemical, Biological, Pharmaceutical and Environmental Sciences, University of Messina, 98122 Messina, Italy
| | - Serena Tamburino
- Chi.Pla Chirurgia Plastica, Via Suor Maria Mazzarello, 54, 95128 Catania, Italy
| | - Rosalba Parenti
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
| | - Rosario Giuffrida
- Department of Biomedical and Biotechnological Sciences, University of Catania, 95123 Catania, Italy
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Nano porous polycarbonate membranes stimulating cell adhesion and promoting osteogenic differentiation and differential mRNA expression. Biochem Biophys Res Commun 2023; 638:147-154. [PMID: 36459878 DOI: 10.1016/j.bbrc.2022.11.022] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/25/2022] [Revised: 11/02/2022] [Accepted: 11/09/2022] [Indexed: 11/13/2022]
Abstract
Tissue engineering is thought to be the ideal therapy for bone defect reconstructive treatment. In this study, we present a method of utilizing micro/nano porous polycarbonate membranes (PCMs) as the extracellular matrix to cultivate the human periodontal ligament cells (hPDLCs) and investigate the osteogenic differentiation of those cells. We also compared the osteogenic enhancing abilities of different pore size PCMs. The pore diameters of the candidate membranes are 200 nm, 800 nm, 1200 nm, and 10 μm respectively, and their physical properties are identified. After seeding and cultivating on the PCMs, hPDLCs can be stimulated to undergo osteogenic differentiation, in which the 200 nm PCM is proved to have the most optimal osteo-induction ability. The results of in vivo experiments provide strong evidence suggesting that the hPDLCs stimulated by 200 nm PCM greatly accelerates the healing of bone reconstruction in mice skull defects, as well as promote the process of ectopic osteogenesis. RNA-sequencing was conducted to determine the differential mRNA expression profile during the osteogenesis process of hPDLCs on PCMs. GO and KEGG enrichment analysis were conducted to study the regulatory mechanisms, in which osteogenic marker expression such as Hippo, TGF-β, and PI3K-Akt signaling pathways were significantly up-regulated. The up-regulation indicates the promising potential of nano porous PCMs for promoting osteogenesis for bone regeneration applications. Ultimately, signaling pathways that promote osteogenesis warrants further exploration.
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Alginates Combined with Natural Polymers as Valuable Drug Delivery Platforms. Mar Drugs 2022; 21:md21010011. [PMID: 36662184 PMCID: PMC9861938 DOI: 10.3390/md21010011] [Citation(s) in RCA: 17] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2022] [Revised: 12/19/2022] [Accepted: 12/20/2022] [Indexed: 12/28/2022] Open
Abstract
Alginates (ALG) have been used in biomedical and pharmaceutical technologies for decades. ALG are natural polymers occurring in brown algae and feature multiple advantages, including biocompatibility, low toxicity and mucoadhesiveness. Moreover, ALG demonstrate biological activities per se, including anti-hyperlipidemic, antimicrobial, anti-reflux, immunomodulatory or anti-inflammatory activities. ALG are characterized by gelling ability, one of the most frequently utilized properties in the drug form design. ALG have numerous applications in pharmaceutical technology that include micro- and nanoparticles, tablets, mucoadhesive dosage forms, wound dressings and films. However, there are some shortcomings, which impede the development of modified-release dosage forms or formulations with adequate mechanical strength based on pure ALG. Other natural polymers combined with ALG create great potential as drug carriers, improving limitations of ALG matrices. Therefore, in this paper, ALG blends with pectins, chitosan, gelatin, and carrageenans were critically reviewed.
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Zheng G, Ma HW, Xiang GH, He GL, Cai HC, Dai ZH, Chen YL, Lin Y, Xu HZ, Ni WF, Xu C, Liu HX, Wang XY. Bone-targeting delivery of platelet lysate exosomes ameliorates glucocorticoid-induced osteoporosis by enhancing bone-vessel coupling. J Nanobiotechnology 2022; 20:220. [PMID: 36310171 PMCID: PMC9620632 DOI: 10.1186/s12951-022-01400-1] [Citation(s) in RCA: 27] [Impact Index Per Article: 9.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2021] [Accepted: 03/26/2022] [Indexed: 11/06/2022] Open
Abstract
BACKGROUND Glucocorticoids (GCs) overuse is associated with decreased bone mass and osseous vasculature destruction, leading to severe osteoporosis. Platelet lysates (PL) as a pool of growth factors (GFs) were widely used in local bone repair by its potent pro-regeneration and pro-angiogenesis. However, it is still seldom applied for treating systemic osteopathia due to the lack of a suitable delivery strategy. The non-targeted distribution of GFs might cause tumorigenesis in other organs. RESULTS In this study, PL-derived exosomes (PL-exo) were isolated to enrich the platelet-derived GFs, followed by conjugating with alendronate (ALN) grafted PEGylated phospholipid (DSPE-PEG-ALN) to establish a bone-targeting PL-exo (PL-exo-ALN). The in vitro hydroxyapatite binding affinity and in vivo bone targeting aggregation of PL-exo were significantly enhanced after ALN modification. Besides directly modulating the osteogenic and angiogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and endothelial progenitor cells (EPCs), respectively, PL-exo-ALN also facilitate their coupling under GCs' stimulation. Additionally, intravenous injection of PL-exo-ALN could successfully rescue GCs induced osteoporosis (GIOP) in vivo. CONCLUSIONS PL-exo-ALN may be utilized as a novel nanoplatform for precise infusion of GFs to bone sites and exerts promising therapeutic potential for GIOP.
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Affiliation(s)
- Gang Zheng
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
| | - Hai-Wei Ma
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
| | - Guang-Heng Xiang
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
| | - Gao-Lu He
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
| | - Han-Chen Cai
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
| | - Zi-Han Dai
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
| | - Yan-Lin Chen
- Department of Orthopaedic Surgery, Lishui Central Hospital and Fifth Affiliated Hospital of Wenzhou Medical University, Lishui, 323000, Zhejiang Province, China
| | - Yan Lin
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
| | - Hua-Zi Xu
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China
| | - Wen-Fei Ni
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
| | - Cong Xu
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
| | - Hai-Xiao Liu
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
| | - Xiang-Yang Wang
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
- The Second School of Medicine, Wenzhou Medical University, Wenzhou, 325000, Zhejiang Province, China.
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Venkatesan J, Murugan SS, Ad P, Dgv Y, Seong GH. Alginate-based Composites Microspheres: Preparations and Applications for Bone Tissue Engineering. Curr Pharm Des 2022; 28:1067-1081. [PMID: 35593346 DOI: 10.2174/1381612828666220518142911] [Citation(s) in RCA: 11] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2021] [Accepted: 01/19/2022] [Indexed: 11/22/2022]
Abstract
Alginate-based biomaterials have been extensively studied for bone tissue engineering. Scaffolds, microspheres, and hydrogels can be developed using alginate, which is biocompatible, biodegradable, and able to deliver growth factors and drugs. Alginate microspheres can be produced using crosslinking, microfluidic, three-dimensional printing, extrusion, and emulsion methods. The sizes of the alginate microspheres range from 10 µm to 4 mm. This review describes the chemical characterization and mechanical assessment of alginate-based microspheres. Combinations of alginate with hydroxyapatite, chitosan, collagen, polylactic acid, polycaprolactone, and bioglass were discussed for bone tissue repair and regeneration. In addition, alginate combinations with bone morphogenetic proteins, vascular endothelial growth factor, transforming growth factor beta-3, other growth factors, cells, proteins, drugs, and osteoinductive drugs were analyzed for tissue engineering applications. Furthermore, the biocompatibility of developed alginate microspheres was discussed for different cell lines. Finally, alginate microsphere-based composites with stem cell interaction for bone tissue regeneration were presented. In the present review, we have assessed the preclinical research on in vivo models of alginate-based microspheres for bone tissue repair and regeneration. Overall, alginate-based microspheres are potential candidates for graft substitutes and the treatment of various bone-related diseases.
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Affiliation(s)
- Jayachandran Venkatesan
- Department of Bionano Engineering, Center for Bionano Intelligence Education and Research, Hanyang University, ERICA, Ansan 426-791, South Korea.,Biomaterials Research Laboratory, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
| | - Sesha Subramanian Murugan
- Department of Bionano Engineering, Center for Bionano Intelligence Education and Research, Hanyang University, ERICA, Ansan 426-791, South Korea
| | - Pandurang Ad
- Department of Bionano Engineering, Center for Bionano Intelligence Education and Research, Hanyang University, ERICA, Ansan 426-791, South Korea
| | - Yashaswini Dgv
- Department of Bionano Engineering, Center for Bionano Intelligence Education and Research, Hanyang University, ERICA, Ansan 426-791, South Korea
| | - Gi Hun Seong
- Biomaterials Research Laboratory, Yenepoya Research Centre, Yenepoya (Deemed to be University), Deralakatte, Mangaluru, 575018, India
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Hua Z, Li S, Liu Q, Yu M, Liao M, Zhang H, Xiang X, Wu Q. Low-Intensity Pulsed Ultrasound Promotes Osteogenic Potential of iPSC-Derived MSCs but Fails to Simplify the iPSC-EB-MSC Differentiation Process. Front Bioeng Biotechnol 2022; 10:841778. [PMID: 35656194 PMCID: PMC9152674 DOI: 10.3389/fbioe.2022.841778] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Key Words] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/22/2021] [Accepted: 04/07/2022] [Indexed: 11/29/2022] Open
Abstract
Induced pluripotent stem cell (iPSC)-derived mesenchymal stem cells (iMSCs) are a promising cell source for bone tissue engineering. However, iMSCs have less osteogenic potential than BMSCs, and the classical iPSC-EB-iMSC process to derive iMSCs from iPSCs is too laborious as it involves multiple in vitro steps. Low-intensity pulsed ultrasound (LIPUS) is a safe therapeutic modality used to promote osteogenic differentiation of stem cells. Whether LIPUS can facilitate osteogenic differentiation of iMSCs and simplify the iPSC-EB-iMSC process is unknown. We stimulated iMSCs with LIPUS at different output intensities (20, 40, and 60 mW/cm2) and duty cycles (20, 50, and 80%). Results of ALP activity assay, osteogenic gene expression, and mineralization quantification demonstrated that LIPUS was able to promote osteogenic differentiation of iMSCs, and it worked best at the intensity of 40 mW/cm2 and the duty cycle of 50% (LIPUS40/50). The Wnt/β-catenin signaling pathway was involved in LIPUS40/50-mediated osteogenesis. When cranial bone defects were implanted with iMSCs, LIPUS40/50 stimulation resulted in a significant higher new bone filling rate (72.63 ± 17.04)% than the non-stimulated ones (34.85 ± 4.53)%. Daily exposure to LIPUS40/50 may accelerate embryoid body (EB)-MSC transition, but it failed to drive iPSCs or EB cells to an osteogenic lineage directly. This study is the first to demonstrate the pro-osteogenic effect of LIPUS on iMSCs. Although LIPUS40/50 failed to simplify the classical iPSC-EB-MSC differentiation process, our preliminary results suggest that LIPUS with a more suitable parameter set may achieve the goal. LIPUS is a promising method to establish an efficient model for iPSC application.
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Affiliation(s)
| | | | | | | | | | | | | | - Qingqing Wu
- *Correspondence: Qingqing Wu, ; Xuerong Xiang,
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10
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Le Q, Madhu V, Hart JM, Farber CR, Zunder ER, Dighe AS, Cui Q. Current evidence on potential of adipose derived stem cells to enhance bone regeneration and future projection. World J Stem Cells 2021; 13:1248-1277. [PMID: 34630861 PMCID: PMC8474721 DOI: 10.4252/wjsc.v13.i9.1248] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/28/2021] [Revised: 05/22/2021] [Accepted: 08/18/2021] [Indexed: 02/06/2023] Open
Abstract
Injuries to the postnatal skeleton are naturally repaired through successive steps involving specific cell types in a process collectively termed “bone regeneration”. Although complex, bone regeneration occurs through a series of well-orchestrated stages wherein endogenous bone stem cells play a central role. In most situations, bone regeneration is successful; however, there are instances when it fails and creates non-healing injuries or fracture nonunion requiring surgical or therapeutic interventions. Transplantation of adult or mesenchymal stem cells (MSCs) defined by the International Society for Cell and Gene Therapy (ISCT) as CD105+CD90+CD73+CD45-CD34-CD14orCD11b-CD79αorCD19-HLA-DR- is being investigated as an attractive therapy for bone regeneration throughout the world. MSCs isolated from adipose tissue, adipose-derived stem cells (ADSCs), are gaining increasing attention since this is the most abundant source of adult stem cells and the isolation process for ADSCs is straightforward. Currently, there is not a single Food and Drug Administration (FDA) approved ADSCs product for bone regeneration. Although the safety of ADSCs is established from their usage in numerous clinical trials, the bone-forming potential of ADSCs and MSCs, in general, is highly controversial. Growing evidence suggests that the ISCT defined phenotype may not represent bona fide osteoprogenitors. Transplantation of both ADSCs and the CD105- sub-population of ADSCs has been reported to induce bone regeneration. Most notably, cells expressing other markers such as CD146, AlphaV, CD200, PDPN, CD164, CXCR4, and PDGFRα have been shown to represent osteogenic sub-population within ADSCs. Amongst other strategies to improve the bone-forming ability of ADSCs, modulation of VEGF, TGF-β1 and BMP signaling pathways of ADSCs has shown promising results. The U.S. FDA reveals that 73% of Investigational New Drug applications for stem cell-based products rely on CD105 expression as the “positive” marker for adult stem cells. A concerted effort involving the scientific community, clinicians, industries, and regulatory bodies to redefine ADSCs using powerful selection markers and strategies to modulate signaling pathways of ADSCs will speed up the therapeutic use of ADSCs for bone regeneration.
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Affiliation(s)
- Quang Le
- Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, United States
| | - Vedavathi Madhu
- Orthopaedic Surgery Research, Thomas Jefferson University, Philadelphia, PA 19107, United States
| | - Joseph M Hart
- Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, United States
| | - Charles R Farber
- Center for Public Health Genomics, University of Virginia, Charlottesville, VA 22908, United States
- Departments of Public Health Sciences and Biochemistry and Molecular Genetics, University of Virginia, Charlottesville, VA 22908, United States
| | - Eli R Zunder
- Department of Biomedical Engineering, University of Virginia, Charlottesville, VA 22908, United States
| | - Abhijit S Dighe
- Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, United States
| | - Quanjun Cui
- Department of Orthopaedic Surgery, University of Virginia School of Medicine, Charlottesville, VA 22908, United States
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11
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Xie C, Ye J, Liang R, Yao X, Wu X, Koh Y, Wei W, Zhang X, Ouyang H. Advanced Strategies of Biomimetic Tissue-Engineered Grafts for Bone Regeneration. Adv Healthc Mater 2021; 10:e2100408. [PMID: 33949147 DOI: 10.1002/adhm.202100408] [Citation(s) in RCA: 81] [Impact Index Per Article: 20.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/04/2021] [Revised: 04/16/2021] [Indexed: 12/21/2022]
Abstract
The failure to repair critical-sized bone defects often leads to incomplete regeneration or fracture non-union. Tissue-engineered grafts have been recognized as an alternative strategy for bone regeneration due to their potential to repair defects. To design a successful tissue-engineered graft requires the understanding of physicochemical optimization to mimic the composition and structure of native bone, as well as the biological strategies of mimicking the key biological elements during bone regeneration process. This review provides an overview of engineered graft-based strategies focusing on physicochemical properties of materials and graft structure optimization from macroscale to nanoscale to further boost bone regeneration, and it summarizes biological strategies which mainly focus on growth factors following bone regeneration pattern and stem cell-based strategies for more efficient repair. Finally, it discusses the current limitations of existing strategies upon bone repair and highlights a promising strategy for rapid bone regeneration.
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Affiliation(s)
- Chang Xie
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310058 China
- Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 314499 China
- Department of Sports Medicine Zhejiang University School of Medicine Hangzhou 310058 China
| | - Jinchun Ye
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310058 China
- Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 314499 China
| | - Renjie Liang
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310058 China
- Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 314499 China
| | - Xudong Yao
- The Fourth Affiliated Hospital Zhejiang University School of Medicine Yiwu 322000 China
| | - Xinyu Wu
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310058 China
- Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 314499 China
| | - Yiwen Koh
- Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 314499 China
| | - Wei Wei
- Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 314499 China
- China Orthopedic Regenerative Medicine Group (CORMed) Hangzhou 310058 China
| | - Xianzhu Zhang
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310058 China
- Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 314499 China
| | - Hongwei Ouyang
- Dr. Li Dak Sum & Yip Yio Chin Center for Stem Cells and Regenerative Medicine and Department of Orthopedic Surgery of the Second Affiliated Hospital Zhejiang University School of Medicine Hangzhou 310058 China
- Zhejiang University‐University of Edinburgh Institute Zhejiang University School of Medicine and Key Laboratory of Tissue Engineering and Regenerative Medicine of Zhejiang Province Zhejiang University School of Medicine Hangzhou 314499 China
- Department of Sports Medicine Zhejiang University School of Medicine Hangzhou 310058 China
- China Orthopedic Regenerative Medicine Group (CORMed) Hangzhou 310058 China
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12
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Li G, Shen W, Tang X, Mo G, Yao L, Wang J. Combined use of calcium phosphate cement, mesenchymal stem cells and platelet-rich plasma for bone regeneration in critical-size defect of the femoral condyle in mini-pigs. Regen Med 2021; 16:451-464. [PMID: 34030462 DOI: 10.2217/rme-2020-0099] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022] Open
Abstract
Aim: To investigate the outcome of autologous bone marrow mesenchymal stem cells (BMMSCs) and platelet-rich plasma in combination with calcium phosphate cement (CPC) scaffold to reconstruct femoral critical bone defects in mini-pigs. Materials & methods: Scanning electron microscopy, micro-computed tomography evaluation and quantitative histological assessment were used. Results & conclusion: BMMSCs were attached to the CPC scaffold after 7 days of culture and decreased the residual CPC material in each group at 12 weeks compared with 6 weeks. The newly formed bone area was higher in the CPC+SC+P group than in the CPC group at each time point (all p < 0.05). The strategy of CPC combined with BMMSCs and platelet-rich plasma might be an effective method to repair bone defects.
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Affiliation(s)
- Guangjun Li
- Department of Orthopedic, Deqing People's Hospital, Deqing, Zhejiang 313200, PR China
| | - Wen Shen
- Department of Radiology, Deqing People's Hospital, Deqing, Zhejiang 313200, PR China
| | - Xing Tang
- Department of Orthopedic, Deqing People's Hospital, Deqing, Zhejiang 313200, PR China
| | - Guowei Mo
- Department of Orthopedic, Deqing People's Hospital, Deqing, Zhejiang 313200, PR China
| | - Liqin Yao
- Department of Orthopedic, Deqing People's Hospital, Deqing, Zhejiang 313200, PR China
| | - Jixing Wang
- Department of Spinal Surgery, Nanfang Hospital, Southern Medical University, Guangzhou, Guangdong 510515, PR China
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13
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Xu Y, Yang Y, Hua Z, Li S, Yang Z, Liu Q, Fu G, Ji P, Wu Q. BMP2 immune complexes promote new bone formation by facilitating the direct contact between osteoclasts and osteoblasts. Biomaterials 2021; 275:120890. [PMID: 34130144 DOI: 10.1016/j.biomaterials.2021.120890] [Citation(s) in RCA: 25] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/27/2020] [Revised: 04/22/2021] [Accepted: 05/06/2021] [Indexed: 11/17/2022]
Abstract
BMP2 antibody is proposed as a promising replacement for rhBMP2 in bone tissue engineering. Although studies have demonstrated its osteoinductive efficacy, the underlying osteogenic mechanism and adverse reactions of specific BMP2 antibody are not clarified yet, making it difficult to optimize the antibody for future application. By establishing BMP2 immune complexes (BMP2-ICs) ex vivo, we were able to introduce BMP2-ICs directly in vivo and found that BMP2-ICs promoted bone formation while suppressing osteoclastogenesis. However, ex vivo osteoclastogenic assays showed that BMP2-ICs promoted osteoclastogenesis by binding FcγR and activating PLCγ2 phosphorylation. Given that BMP2-ICs react with osteoblast and osteoclast lineage cells by the conjugated BMP2 domain and the Fc domain respectively, we introduced BMP2-ICs into coculture system of the two lineage cells and found that BMP2-ICs promoted osteogenesis while suppressing osteoclastogenesis by facilitating osteoblast-osteoclast contact and activating the EphrinB2-EphB4 signaling. This bidirectional function of BMP2-ICs was reproduced in the cranial bone resorption model, where osteoblast and osteoclast lineage cells co-localized. This study excluded the hidden problem of osteoclast overactivation that usually comes with rhBMP2 and clarified the first evidence of the mechanism of antibody-mediated bone regeneration, suggesting BMP2-ICs may present a promising therapy for bone diseases related with disrupted osteoclast-osteoblast interaction.
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Affiliation(s)
- Yamei Xu
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Yao Yang
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Ziyi Hua
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Shuang Li
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Zhenyu Yang
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Qianzi Liu
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Gang Fu
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China; Department of Oral Implantology, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China
| | - Ping Ji
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China
| | - Qingqing Wu
- Stomatological Hospital of Chongqing Medical University, Chongqing Key Laboratory of Oral Diseases and Biomedical Sciences, Chongqing Municipal Key Laboratory of Oral Biomedical Engineering of Higher Education, Chongqing, 401147, China; Department of Oral Implantology, Stomatological Hospital of Chongqing Medical University, Chongqing, 401147, China.
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14
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Kulanthaivel S, Agarwal T, Sharan Rathnam VS, Pal K, Banerjee I. Cobalt doped nano-hydroxyapatite incorporated gum tragacanth-alginate beads as angiogenic-osteogenic cell encapsulation system for mesenchymal stem cell based bone tissue engineering. Int J Biol Macromol 2021; 179:101-115. [PMID: 33621571 DOI: 10.1016/j.ijbiomac.2021.02.136] [Citation(s) in RCA: 11] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/20/2020] [Revised: 02/10/2021] [Accepted: 02/18/2021] [Indexed: 12/14/2022]
Abstract
Angiogenic-osteogenic cell encapsulation system is a technical need for human mesenchymal stem cell (hMSC)-based bone tissue engineering (BTE). Here, we have developed a highly efficient hMSC encapsulation system by incorporating bivalent cobalt doped nano-hydroxyapatite (HAN) and gum tragacanth (GT) as angiogenic-osteogenic components into the calcium alginate (CA) beads. Physico-chemical characterizations revealed that the swelling and degradation of HAN incorporated CA-GT beads (GT-HAN) were 1.34 folds and 2 folds higher than calcium alginate (CA) beads. Furthermore, the diffusion coefficient of solute molecule was found 2.5-fold higher in GT-HAN with respect to CA bead. It is observed that GT-HAN supports the long-term viability of encapsulated hMSC and causes 50% less production of reactive oxygen species (ROS) in comparison to CA beads. The expression of osteogenic differentiation markers was found 1.5-2.5 folds higher in the case of GT-HAN in comparison to CA. A similar trend was observed for hypoxia inducible factor 1 alpha (HIF-1α) and vascular endothelial growth factor (VEGF). The soluble secretome from hMSC encapsulated in the GT-HAN induced proliferation of endothelial cells and supported tube formation (2.5-fold higher than CA beads). These results corroborated that GT-HAN could be used as an angiogenic-osteogenic cell encapsulation matrix for hMSC encapsulation and BTE application.
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Affiliation(s)
- Senthilguru Kulanthaivel
- Department of Biochemical Engineering and Biotechnology, Indian Institute of Technology Delhi, New Delhi 110016, India
| | - Tarun Agarwal
- Department of Biotechnology, Indian Institute of Technology Kharagpur, West Bengal 721302, India
| | - V S Sharan Rathnam
- Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha 769008, India
| | - Kunal Pal
- Department of Biotechnology and Medical Engineering, National Institute of Technology, Rourkela, Odisha 769008, India
| | - Indranil Banerjee
- Department of Bioscience and Bioengineering, Indian Institute of Technology Jodhpur, Rajasthan 342037, India.
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15
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Preparation of Alginate-Based Biomaterials and Their Applications in Biomedicine. Mar Drugs 2021; 19:md19050264. [PMID: 34068547 PMCID: PMC8150954 DOI: 10.3390/md19050264] [Citation(s) in RCA: 156] [Impact Index Per Article: 39.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2021] [Revised: 04/26/2021] [Accepted: 04/30/2021] [Indexed: 12/14/2022] Open
Abstract
Alginates are naturally occurring polysaccharides extracted from brown marine algae and bacteria. Being biocompatible, biodegradable, non-toxic and easy to gel, alginates can be processed into various forms, such as hydrogels, microspheres, fibers and sponges, and have been widely applied in biomedical field. The present review provides an overview of the properties and processing methods of alginates, as well as their applications in wound healing, tissue repair and drug delivery in recent years.
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16
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Alginate microgels as delivery vehicles for cell-based therapies in tissue engineering and regenerative medicine. Carbohydr Polym 2021; 266:118128. [PMID: 34044944 DOI: 10.1016/j.carbpol.2021.118128] [Citation(s) in RCA: 45] [Impact Index Per Article: 11.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/07/2020] [Revised: 04/15/2021] [Accepted: 04/25/2021] [Indexed: 12/26/2022]
Abstract
Conventional stem cell delivery typically utilize administration of directly injection of allogenic cells or domesticated autogenic cells. It may lead to immune clearance of these cells by the host immune systems. Alginate microgels have been demonstrated to improve the survival of encapsulated cells and overcome rapid immune clearance after transplantation. Moreover, alginate microgels can serve as three-dimensional extracellular matrix to support cell growth and protect allogenic cells from rapid immune clearance, with functions as delivery vehicles to achieve sustained release of therapeutic proteins and growth factors from the encapsulated cells. Besides, cell-loaded alginate microgels can potentially be applied in regenerative medicine by serving as injectable engineered scaffolds to support tissue regrowth. In this review, the properties of alginate and different methods to produce alginate microgels are introduced firstly. Then, we focus on diverse applications of alginate microgels for cell delivery in tissue engineering and regenerative medicine.
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17
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Najdanović JG, Cvetković VJ, Stojanović ST, Vukelić-Nikolić MĐ, Živković JM, Najman SJ. Vascularization and osteogenesis in ectopically implanted bone tissue-engineered constructs with endothelial and osteogenic differentiated adipose-derived stem cells. World J Stem Cells 2021; 13:91-114. [PMID: 33584982 PMCID: PMC7859989 DOI: 10.4252/wjsc.v13.i1.91] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/12/2020] [Revised: 11/01/2020] [Accepted: 11/17/2020] [Indexed: 02/06/2023] Open
Abstract
BACKGROUND A major problem in the healing of bone defects is insufficient or absent blood supply within the defect. To overcome this challenging problem, a plethora of approaches within bone tissue engineering have been developed recently. Bearing in mind that the interplay of various diffusible factors released by endothelial cells (ECs) and osteoblasts (OBs) have a pivotal role in bone growth and regeneration and that adjacent ECs and OBs also communicate directly through gap junctions, we set the focus on the simultaneous application of these cell types together with platelet-rich plasma (PRP) as a growth factor reservoir within ectopic bone tissue engineering constructs.
AIM To vascularize and examine osteogenesis in bone tissue engineering constructs enriched with PRP and adipose-derived stem cells (ASCs) induced into ECs and OBs.
METHODS ASCs isolated from adipose tissue, induced in vitro into ECs, OBs or just expanded were used for implant construction as followed: BPEO, endothelial and osteogenic differentiated ASCs with PRP and bone mineral matrix; BPUI, uninduced ASCs with PRP and bone mineral matrix; BC (control), only bone mineral matrix. At 1, 2, 4 and 8 wk after subcutaneous implantation in mice, implants were extracted and endothelial-related and bone-related gene expression were analyzed, while histological analyses were performed after 2 and 8 wk.
RESULTS The percentage of vascularization was significantly higher in BC compared to BPUI and BPEO constructs 2 and 8 wk after implantation. BC had the lowest endothelial-related gene expression, weaker osteocalcin immunoexpression and Spp1 expression compared to BPUI and BPEO. Endothelial-related gene expression and osteocalcin immunoexpression were higher in BPUI compared to BC and BPEO. BPEO had a higher percentage of vascularization compared to BPUI and the highest CD31 immunoexpression among examined constructs. Except Vwf, endothelial-related gene expression in BPEO had a later onset and was upregulated and well-balanced during in vivo incubation that induced late onset of Spp1 expression and pronounced osteocalcin immunoexpression at 2 and 8 wk. Tissue regression was noticed in BPEO constructs after 8 wk.
CONCLUSION Ectopically implanted BPEO constructs had a favorable impact on vascularization and osteogenesis, but tissue regression imposed the need for discovering a more optimal EC/OB ratio prior to considerations for clinical applications.
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Affiliation(s)
- Jelena G Najdanović
- Department of Biology and Human Genetics; Department for Cell and Tissue Engineering, Faculty of Medicine, University of Niš, Niš 18108, Serbia
| | - Vladimir J Cvetković
- Department of Biology and Ecology, Faculty of Sciences and Mathematics, University of Niš, Niš 18106, Serbia
| | - Sanja T Stojanović
- Department of Biology and Human Genetics; Department for Cell and Tissue Engineering, Faculty of Medicine, University of Niš, Niš 18108, Serbia
| | - Marija Đ Vukelić-Nikolić
- Department of Biology and Human Genetics; Scientific Research Center for Biomedicine; Faculty of Medicine, University of Niš, Niš 18108, Serbia
| | - Jelena M Živković
- Department of Biology and Human Genetics; Scientific Research Center for Biomedicine; Faculty of Medicine, University of Niš, Niš 18108, Serbia
| | - Stevo J Najman
- Department of Biology and Human Genetics; Department for Cell and Tissue Engineering, Faculty of Medicine, University of Niš, Niš 18108, Serbia
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18
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Stramandinoli-Zanicotti RT, Sassi LM, Rebelatto CLK, Boldrine-Leite LM, Brofman PR, Carvalho AL. The effect of bone marrow-derived stem cells associated with platelet-rich plasma on the osseointegration of immediately placed implants. J Clin Exp Dent 2021; 13:e8-e13. [PMID: 33425225 PMCID: PMC7781218 DOI: 10.4317/jced.56743] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/02/2020] [Accepted: 05/14/2020] [Indexed: 01/30/2023] Open
Abstract
Background Stem cells associated with growth factors have been shown to improve bone healing and the osseointegration of dental implants. A Brazilian miniature pig model was used to evaluate the effect of autologous bone marrow-derived mesenchymal stem cells (BM-MSCs) associated with platelet-rich plasma (PRP) on the osseointegration of immediately placed dental implants.
Material and Methods A total of four male adult miniature pigs were used in this study. BM-MSCs from each pig were isolated from the iliac crest and expanded in vitro. The undifferentiated BM-MSCs were mixed with autologous PRP and implanted in the post-extraction sockets at the experimental sites before implant placement (10 x 106 cells/ socket). The control sites did not receive either BM-MSC or PRP. Each animal received four implants in the control side and 04 on the experimental side, totalizing 32 implants. The specimens were analyzed radiographically and histomorphometrically to determine the implant loss rate (ILR), the bone-implant contact (BIC), and bone density within the threads (BDWT).
Results The ILR, the BIC, and the BDWT for the control and experimental sites were respectively 25.0% and 18.7% (p=0.686); 39.0% and 27.7% (p=0.110); 46.8% and 36.5% (p=0.247).
Conclusions The use of BM-MSCs + PRP in conjunction with immediately placed implants showed a lower ILR but there was no significant effect on the osseointegration of the dental implants. More preclinical studies, in large animal models, are needed to establish whether BM-MSCs associated with PRP could be used for the enhancement of the osseointegration of dental implants. Key words:Osseointegration, bone marrow-derived mesenchymal stem cells, platelet-rich plasma, dental implants, minipigs.
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Affiliation(s)
- Roberta-Targa Stramandinoli-Zanicotti
- Postgraduate Program in Oncology, University of São Paulo, São Paulo, SP, Brazil; Oral and Maxillofacial Surgery Department, Erasto Gaertner Hospital, Curitiba, PR, Brazil
| | - Laurindo-Moacir Sassi
- Oral and Maxillofacial Surgery Department, Erasto Gaertner Hospital, Curitiba, PR, Brazil
| | | | - Lidiane M Boldrine-Leite
- Experimental Laboratory of Cell Culture, Pontifical Catholic University of Paraná (PUC-PR), Curitiba, PR, Brazil
| | - Paulo-Roberto Brofman
- Experimental Laboratory of Cell Culture, Pontifical Catholic University of Paraná (PUC-PR), Curitiba, PR, Brazil
| | - Andre-Lopes Carvalho
- Research Advisor of Postgraduate Program in Oncology, Medical School of University of São Paulo (FMUSP), São Paulo, SP, Brazil
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Tang Q, Lim T, Shen LY, Zheng G, Wei XJ, Zhang CQ, Zhu ZZ. Well-dispersed platelet lysate entrapped nanoparticles incorporate with injectable PDLLA-PEG-PDLLA triblock for preferable cartilage engineering application. Biomaterials 2020; 268:120605. [PMID: 33360073 DOI: 10.1016/j.biomaterials.2020.120605] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 06/19/2020] [Revised: 12/08/2020] [Accepted: 12/11/2020] [Indexed: 01/02/2023]
Abstract
Platelet lysate (PL) as a cost-effective cocktail of growth factors is an emerging ingredient in regenerative medicine, especially in cartilage tissue engineering. However, most studies fail to pay attention to PL's intrinsic characteristics and incorporate it directly with scaffolds or hydrogels by simple mixture. Currently, the particle size distribution of PL was determined to be scattered. Directly introducing PL into a thermosensitive poly(d,l-lactide)-poly(ethylene glycol)-poly(d,l-lactide) (PLEL) hydrogel disturbed its sol-gel transition. Electrostatic self-assembly heparin (Hep) and ε-poly-l-lysine (EPL) nanoparticles (NPs) were fabricated to improve the dispersity of PL. Such PL-NPs-incorporated PLEL gels retained the initial gelling capacity and showed a long-term PL-releasing ability. Moreover, the PL-loaded composite hydrogels inhibited the inflammatory response and dedifferentiation of IL-1β-induced chondrocytes. For in vivo applications, the PLEL@PL-NPs system ameliorated the early cartilage degeneration and promoted cartilage repair in the late stage of osteoarthritis. RNA sequencing analysis indicated that PL's protective effects might be associated with modulating hyaluronan synthase 1 (HAS-1) expression. Taken together, these results suggest that well-dispersed PL by Hep/EPL NPs is a preferable approach for its incorporation into hydrogels and the constructed PLEL@PL-NPs system is a promising cell-free and stepwise treatment option for cartilage tissue engineering.
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Affiliation(s)
- Qian Tang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Thou Lim
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China
| | - Li-Yan Shen
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China
| | - Gang Zheng
- Key Laboratory of Orthopaedics of Zhejiang Province, Department of Orthopaedics, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, 109, Xueyuanxi Road, 325027 Wenzhou, China
| | - Xiao-Juan Wei
- Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
| | - Chang-Qing Zhang
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
| | - Zhen-Zhong Zhu
- Department of Orthopedic Surgery, Shanghai Jiao Tong University Affiliated Shanghai Sixth People's Hospital, 600 Yishan Road, Shanghai 200233, China.
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20
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Chen J, Li W, Li Q, Wang Y, Zhao B, Han X, Deng J, Liu Y. The composite sandwich structure of dNCPs polyelectrolyte multilayers induced the osteogenic differentiation of PDLSCs in vitro. J Appl Biomater Funct Mater 2020; 18:2280800020942719. [PMID: 33176539 DOI: 10.1177/2280800020942719] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/15/2022] Open
Abstract
This study reported about the fabrication of dentin non-collagenous proteins (dNCPs) polyelectrolyte multilayers and evaluated its osteogenic potential. The composite sandwich structure of dNCPs polyelectrolyte multilayers was generated on the surface of polycaprolactone electrospinning membranes by the Layer-by-Layer self-assembly technique. The dNCPs-coated membranes comprised the experimental group and the non-coated membranes acted as the control. Nanofiber morphologies of both membranes were observed under scanning electron microscope. The release of dNCPs was evaluated by ELISA kit. Periodontal ligament stem cells (PDLSCs) were seeded on both membranes. The morphology changes and proliferation of cells were tested. The expressions of osteogenic-related genes and proteins were evaluated by RT-PCR, alkaline phosphatase (ALP) activity assay, and immunofluorescence staining. dNCPs-coated membranes displayed significantly different fiber morphology than the non-coated membranes. A stable release of dentin phosphoprotein was maintained from day 4 to day 15 in the experimental group. Cells on dNCPs-coated membranes were found to have cuboidal or polygonal shapes. The proliferative rate of cells was significantly lower in the experimental group from day 4 to day 9 (p<0.05). However, cells on the dNCPs-coated membranes demonstrated a significantly higher ALP content and expression levels of osteogenic gene and proteins than the controls (p<0.05). These results indicated that dNCPs polyelectrolyte multilayers could induce the osteogenic differentiation of PDLSCs in vitro.
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Affiliation(s)
- Jing Chen
- Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China.,Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China
| | - Wenxing Li
- Chengdu Zhuoyue dental clinic, Chengdu, P.R. China
| | - Qiang Li
- Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China.,Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China
| | - Yuhui Wang
- Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China.,Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China
| | - Bingjiao Zhao
- Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China.,Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China
| | - Xinxin Han
- Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China
| | - Jiajia Deng
- Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China.,Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China
| | - Yuehua Liu
- Department of Orthodontics, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China.,Oral Biomedical Engineering Laboratory, Shanghai Stomatological Hospital, Fudan University, Shanghai, P.R. China
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21
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Wang J, Xie L, Wang X, Zheng W, Chen H, Cai L, Chen L. The effects of oyster shell/alpha-calcium sulfate hemihydrate/platelet-rich plasma/bone mesenchymal stem cells bioengineering scaffold on rat critical-sized calvarial defects. JOURNAL OF MATERIALS SCIENCE. MATERIALS IN MEDICINE 2020; 31:96. [PMID: 33128637 DOI: 10.1007/s10856-020-06441-2] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/15/2020] [Accepted: 09/24/2020] [Indexed: 06/11/2023]
Abstract
Engineering scaffolds combining natural biomineral and artificially synthesized material hold promising potential for bone tissue regeneration. We fabricated a bioengineering scaffold, oyster shell (OS) and alpha-calcium sulfate hemihydrate (α-CSH) as scaffold, platelet-rich plasma (PRP) as provider of growth factors and bone mesenchymal stem cells (BMSCs) as seed cells, and determined it could be applied as a new type of bone graft substitutes by rat calvarial defects repairing experiment in vitro and in vivo. SEM showed that the mean diameter of the pores was about 150 μm with a range of 50-200 μm, and scaffold's porosity was ~27.4% by Archimedes' Principle. In vitro, Scaffold + BMSCs + PRP group presented a higher ALP activity compared with other groups by ELISA (P < 0.05). But the expression of OC was not detectable on day 4 or 8. The MTT assay showed that the relative cell number of BMSCs+PRP group increased significantly (P < 0.05). In vivo, the smallest defect area of skull and highest volume of regenerated new bone were observed in Scaffold + PRP + BMSCs group by X-ray and Micro-CT analysis (P < 0.05). And the similar results also were observed in HE and Masson staining. The immunohistochemistry staining for osteogenic marker proteins ALP and OC showed that the most obvious positive staining was observed in Scaffold + PRP + BMSCs group (P < 0.05). The expression of inflammatory markers IL-6 and TNF-α was the lowest in control group (P < 0.05). In conclusion, a bioengineering scaffold based on OS, created by simply combining α-CSH and PRP and implanting with BMSCs, could be clinically useful and has marked advantages as a targeted, off-the-shelf, cell-loaded treatment option for the bone healing of critical-size calvarial defects.
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Affiliation(s)
- Jinwu Wang
- Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, XueYuan West Road, Luheng District, Wenzhou, Zhejiang Province, 325000, P.R. China
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Linzhen Xie
- Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, XueYuan West Road, Luheng District, Wenzhou, Zhejiang Province, 325000, P.R. China
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Xingyu Wang
- Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, XueYuan West Road, Luheng District, Wenzhou, Zhejiang Province, 325000, P.R. China
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Wenhao Zheng
- Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, XueYuan West Road, Luheng District, Wenzhou, Zhejiang Province, 325000, P.R. China
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Hua Chen
- Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, XueYuan West Road, Luheng District, Wenzhou, Zhejiang Province, 325000, P.R. China
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Leyi Cai
- Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, XueYuan West Road, Luheng District, Wenzhou, Zhejiang Province, 325000, P.R. China
- Wenzhou Medical University, Wenzhou, Zhejiang, China
| | - Long Chen
- Department of Orthopaedics Surgery, The Second Affiliated Hospital and Yuying Children's Hospital of Wenzhou Medical University, NO.109, XueYuan West Road, Luheng District, Wenzhou, Zhejiang Province, 325000, P.R. China.
- Wenzhou Medical University, Wenzhou, Zhejiang, China.
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22
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Abstract
Keratin-based biomaterials represent an attractive opportunity in the fields of wound healing and tissue regeneration, not only for their chemical and physical properties, but also for their ability to act as a delivery system for a variety of payloads. Importantly, keratins are the only natural biomaterial that is not targeted by specific tissue turnover-related enzymes, giving it potential stability advantages and greater control over degradation after implantation. However, in-situ polymerization chemistry in some keratin systems are not compatible with cells, and incorporation within constructs such as hydrogels may lead to hypoxia and cell death. To address these challenges, we envisioned a pre-formed keratin microparticle on which cells could be seeded, while other payloads (e.g. drugs, growth factors or other biologic compounds) could be contained within, although studies investigating the potential partitioning between phases during emulsion polymerization would need to be conducted. This study employs well-established water-in-oil emulsion procedures as well as a suspension culture method to load keratin-based microparticles with bone marrow-derived mesenchymal stem cells. Fabricated microparticles were characterized for size, porosity and surface structure and further analyzed to investigate their ability to form gels upon hydration. The suspension culture technique was validated based on the ability for loaded cells to maintain their viability and express actin and vinculin proteins, which are key indicators of cell attachment and growth. Maintenance of expression of markers associated with cell plasticity was also investigated. As a comparative model, a collagen-coated microparticle (Sigma) of similar size was used. Results showed that an oxidized form of keratin ("keratose" or "KOS") formed unique microparticle structures of various size that appeared to contain a fibrous sub-structure. Cell adhesion and viability was greater on keratin microparticles compared to collagen-coated microparticles, while marker expression was retained on both.
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Affiliation(s)
- Marc Thompson
- US Army Institute of Surgical Research, Burn and Soft Tissue Research Division, Fort Sam Houston, TX, USA
| | - Aaron Giuffre
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Claire McClenny
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
| | - Mark Van Dyke
- Department of Biomedical Engineering and Mechanics, Virginia Polytechnic Institute and State University, Blacksburg, VA, USA
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23
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Tao J, Liu H, Wu W, Zhang J, Liu S, Zhang J, Huang Y, Xu X, He H, Yang S, Gou M. 3D‐Printed Nerve Conduits with Live Platelets for Effective Peripheral Nerve Repair. ADVANCED FUNCTIONAL MATERIALS 2020. [DOI: 10.1002/adfm.202004272] [Citation(s) in RCA: 39] [Impact Index Per Article: 7.8] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/05/2023]
Affiliation(s)
- Jie Tao
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610065 China
| | - Haofan Liu
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610065 China
| | - Wenbi Wu
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610065 China
| | - Jiumeng Zhang
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610065 China
| | - Sijia Liu
- Department of Rehabilitation Medicine West China Hospital Sichuan University Chengdu 610041 China
| | - Jing Zhang
- Department of Neurosurgery West China Hospital Sichuan University Chengdu 610041 China
| | - Yulan Huang
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610065 China
| | - Xin Xu
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610065 China
| | - Hongchen He
- Department of Rehabilitation Medicine West China Hospital Sichuan University Chengdu 610041 China
| | - Siming Yang
- Key Laboratory of Wound Repair and Regeneration of PLA Chinese PLA General Hospital Medical College of PLA Beijing 100853 China
| | - Maling Gou
- State Key Laboratory of Biotherapy and Cancer Center West China Hospital Sichuan University Chengdu 610065 China
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24
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Wong CC, Liao JH, Sheu SY, Lin PY, Chen CH, Kuo TF. Novel transplant of combined platelet-rich fibrin Releasate and bone marrow stem cells prevent bone loss in Ovariectomized osteoporotic mice. BMC Musculoskelet Disord 2020; 21:527. [PMID: 32770974 PMCID: PMC7415181 DOI: 10.1186/s12891-020-03549-y] [Citation(s) in RCA: 6] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/08/2020] [Accepted: 07/30/2020] [Indexed: 01/02/2023] Open
Abstract
BACKGROUND Osteoporosis is a metabolic bone disorder characterized by deterioration in the quantity and quality of bone tissue, with a consequent increase susceptibility to fracture. METHODS In this study, we sought to determine the efficacy of platelet-rich fibrin releasates (PRFr) in augmenting the therapeutic effects of stem cell-based therapy in treating osteoporotic bone disorder. An osteoporosis mouse model was established through bilateral ovariectomy on 12-week-old female ICR (Institute of Cancer Research) mice. Eight weeks postoperatively, the ovariectomized (OVX) mice were left untreated (control) or injected with PRFr, bone marrow stem cells (BMSCs), or the combination of BMSCs and PRFr. Two different injection (single versus quadruple) dosages were tested to investigate the accumulative effects of BMSCS and PRFr on bone quality. Eight weeks after injection, the changes in tibial microstructural profiles included the percentage of bone volume versus total tissue volume (BV/TV, %), bone mineral density (BMD, g/cm3), trabecular number (Tb.N, number/mm), and trabecular separation (Tb.Sp, mm) and bony histology were analyzed. RESULTS Postmenopausal osteoporosis model was successfully established in OVX mice, evidenced by reduced BMD, decreased BV/TV, lower Tb.N but increased Tb.Sp. Eight weeks after injection, there was no significant change to BMD and bone trabeculae could be detected in mice that received single-injection regimen. In contrast, in mice which received 4 doses of combined PRFr and BMSCs, the BMD, BV/TV, and TB.N increased, and the TB.Sp decreased significantly compared to untreated OVX mice. Moreover, the histological analysis showed the trabecular spacing become narrower in OVX-mice treated with quadruple injection of BMSCs and combined PRFr and BMSCs than untreated control. CONCLUSION The systemic administration of combined BMSCs and PRFr protected against OVX-induced bone mass loss in mice. Moreover, the improvement of bony profile scores in quadruple-injection group is better than the single-injection group, probably through the increase in effect size of cells and growth factors. Our data also revealed the combination therapy of BMSCs and PRFr has better effect in enhancing osteogenesis, which may provide insight for the development of a novel therapeutic strategy in osteoporosis treatment.
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Affiliation(s)
- Chin-Chean Wong
- Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.,Department of Orthopedics, School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.,Research Center of Biomedical Devices, Taipei Medical University, Taipei, 11031, Taiwan.,International Ph.D. Program for Cell Therapy and Regenerative Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan.,Non-invasive Cancer Therapy Research Institute of Taiwan, Taipei, 10489, Taiwan
| | - Jeng-Hao Liao
- School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan
| | - Shi-Yuan Sheu
- School of Chinese Medicine for Post-Baccalaureate, I-Shou University, Kaohsiung, 84001, Taiwan. .,Department of Chinese Medicine, E-Da Cancer Hospital, Kaohsiung, 84001, Taiwan.
| | - Po-Yu Lin
- School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan
| | - Chih-Hwa Chen
- Department of Orthopedics, Shuang Ho Hospital, Taipei Medical University, New Taipei City, 23561, Taiwan.,Research Center of Biomedical Devices, Taipei Medical University, Taipei, 11031, Taiwan.,School of Biomedical Engineering, College of Biomedical Engineering, Taipei Medical University, Taipei, 11031, Taiwan.,School of Medicine, College of Medicine, Taipei Medical University, Taipei, 11031, Taiwan
| | - Tzong-Fu Kuo
- School of Veterinary Medicine, National Taiwan University, Taipei, 10617, Taiwan. .,Department of Post-Baccalaureate Veterinary Medicine, Asia University, Taichung, 41354, Taiwan.
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25
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Filippi M, Born G, Chaaban M, Scherberich A. Natural Polymeric Scaffolds in Bone Regeneration. Front Bioeng Biotechnol 2020; 8:474. [PMID: 32509754 PMCID: PMC7253672 DOI: 10.3389/fbioe.2020.00474] [Citation(s) in RCA: 161] [Impact Index Per Article: 32.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/05/2020] [Accepted: 04/23/2020] [Indexed: 12/13/2022] Open
Abstract
Despite considerable advances in microsurgical techniques over the past decades, bone tissue remains a challenging arena to obtain a satisfying functional and structural restoration after damage. Through the production of substituting materials mimicking the physical and biological properties of the healthy tissue, tissue engineering strategies address an urgent clinical need for therapeutic alternatives to bone autografts. By virtue of their structural versatility, polymers have a predominant role in generating the biodegradable matrices that hold the cells in situ to sustain the growth of new tissue until integration into the transplantation area (i.e., scaffolds). As compared to synthetic ones, polymers of natural origin generally present superior biocompatibility and bioactivity. Their assembly and further engineering give rise to a wide plethora of advanced supporting materials, accounting for systems based on hydrogels or scaffolds with either fibrous or porous architecture. The present review offers an overview of the various types of natural polymers currently adopted in bone tissue engineering, describing their manufacturing techniques and procedures of functionalization with active biomolecules, and listing the advantages and disadvantages in their respective use in order to critically compare their actual applicability potential. Their combination to other classes of materials (such as micro and nanomaterials) and other innovative strategies to reproduce physiological bone microenvironments in a more faithful way are also illustrated. The regeneration outcomes achieved in vitro and in vivo when the scaffolds are enriched with different cell types, as well as the preliminary clinical applications are presented, before the prospects in this research field are finally discussed. The collection of studies herein considered confirms that advances in natural polymer research will be determinant in designing translatable materials for efficient tissue regeneration with forthcoming impact expected in the treatment of bone defects.
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Affiliation(s)
- Miriam Filippi
- Department of Biomedical Engineering, University of Basel, Basel, Switzerland.,Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Gordian Born
- Department of Biomedical Engineering, University of Basel, Basel, Switzerland
| | - Mansoor Chaaban
- Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
| | - Arnaud Scherberich
- Department of Biomedical Engineering, University of Basel, Basel, Switzerland.,Department of Biomedicine, University Hospital Basel, University of Basel, Basel, Switzerland
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26
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Patel BB, McNamara MC, Pesquera-Colom LS, Kozik EM, Okuzonu J, Hashemi NN, Sakaguchi DS. Recovery of Encapsulated Adult Neural Progenitor Cells from Microfluidic-Spun Hydrogel Fibers Enhances Proliferation and Neuronal Differentiation. ACS OMEGA 2020; 5:7910-7918. [PMID: 32309700 PMCID: PMC7160838 DOI: 10.1021/acsomega.9b04214] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 12/09/2019] [Accepted: 03/20/2020] [Indexed: 06/11/2023]
Abstract
Because of the limitations imposed by traditional two-dimensional (2D) cultures, biomaterials have become a major focus in neural and tissue engineering to study cell behavior in vitro. 2D systems fail to account for interactions between cells and the surrounding environment; these cell-matrix interactions are important to guide cell differentiation and influence cell behavior such as adhesion and migration. Biomaterials provide a unique approach to help mimic the native microenvironment in vivo. In this study, a novel microfluidic technique is used to encapsulate adult rat hippocampal stem/progenitor cells (AHPCs) within alginate-based fibrous hydrogels. To our knowledge, this is the first study to encapsulate AHPCs within a fibrous hydrogel. Alginate-based hydrogels were cultured for 4 days in vitro and recovered to investigate the effects of a 3D environment on the stem cell fate. Post recovery, cells were cultured for an additional 24 or 72 h in vitro before fixing cells to determine if proliferation and neuronal differentiation were impacted after encapsulation. The results indicate that the 3D environment created within a hydrogel is one factor promoting AHPC proliferation and neuronal differentiation (19.1 and 13.5%, respectively); however, this effect is acute. By 72 h post recovery, cells had similar levels of proliferation and neuronal differentiation (10.3 and 8.3%, respectively) compared to the control conditions. Fibrous hydrogels may better mimic the natural micro-environment present in vivo and be used to encapsulate AHPCs, enhancing cell proliferation and selective differentiation. Understanding cell behavior within 3D scaffolds may lead to the development of directed therapies for central nervous system repair and rescue.
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Affiliation(s)
- Bhavika B Patel
- Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, United States
- Neuroscience Program, Iowa State University, Ames, Iowa 50011, United States
| | - Marilyn C McNamara
- Department of Mechanical Engineering, Iowa State University, Ames, Iowa 50011, United States
| | - Laura S Pesquera-Colom
- Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, United States
- Biology Program, Iowa State University, Ames, Iowa 50010, United States
| | - Emily M Kozik
- Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, United States
- Biology Program, Iowa State University, Ames, Iowa 50010, United States
| | - Jasmin Okuzonu
- Department of Biological and Chemical Engineering, Iowa State University, Ames, Iowa 50010, United States
| | - Nicole N Hashemi
- Department of Mechanical Engineering, Iowa State University, Ames, Iowa 50011, United States
| | - Donald S Sakaguchi
- Department of Genetics, Development and Cell Biology, Iowa State University, Ames, Iowa 50011, United States
- Neuroscience Program, Iowa State University, Ames, Iowa 50011, United States
- Biology Program, Iowa State University, Ames, Iowa 50010, United States
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27
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Bu S, Yan S, Wang R, Xia P, Zhang K, Li G, Yin J. In Situ Precipitation of Cluster and Acicular Hydroxyapatite onto Porous Poly(γ-benzyl-l-glutamate) Microcarriers for Bone Tissue Engineering. ACS APPLIED MATERIALS & INTERFACES 2020; 12:12468-12477. [PMID: 32091198 DOI: 10.1021/acsami.9b22559] [Citation(s) in RCA: 19] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/10/2023]
Abstract
Bone tissue engineering scaffold based on microcarriers provides an effective approach for the repair of irregular bone defects. The implantation of microcarriers by injection can reduce surgical trauma and fill various irregular shaped bone defects. Microcarriers with porous structure and osteogenic properties have shown great potential in promoting the repair of bone defects. In this study, two kinds of hydroxyapatite/poly-(γ-benzyl-l-glutamate) (HA/PBLG) microcarriers were constructed by emulsion/in situ precipitation method and their structures and properties were studied. First, PBLG porous microcarriers were prepared by an emulsion method. Surface carboxylation of PBLG microcarriers was performed to promote the deposition of HA on PBLG microcarriers. Next, the modified porous PBLG microcarriers were used as the matrix, combined with the in situ precipitation method; the cluster HA and acicular HA were precipitated onto the surface of porous microcarriers in the presence of ammonia water and tri(hydroxymethyl)aminomethane (Tris) solution, respectively. The micromorphology, composition, and element distribution of the two kinds of microcarriers were characterized by TEM, SEM, and AFM. Adipose stem cells (ADSCs) were cultured on the cluster HA/PBLG and acicular HA/PBLG microcarriers, respectively. ADSCs could grow and proliferate normally on both kinds of microcarriers wherein the acicular HA/PBLG microcarriers were more favorable for early cell adhesion and showed a beneficial effect on mineralization and osteogenic differentiation of ADSCs. Successful healing of a rabbit femur defect verified the bone regeneration ability of acicular HA/PBLG microcarriers.
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Affiliation(s)
- Shuai Bu
- Department of Polymer Materials, Shanghai University, 99 Shangda Road, Shanghai 200444, People's Republic of China
| | - Shifeng Yan
- Department of Polymer Materials, Shanghai University, 99 Shangda Road, Shanghai 200444, People's Republic of China
| | - Ruanfeng Wang
- Department of Polymer Materials, Shanghai University, 99 Shangda Road, Shanghai 200444, People's Republic of China
| | - Pengfei Xia
- Department of Polymer Materials, Shanghai University, 99 Shangda Road, Shanghai 200444, People's Republic of China
| | - Kunxi Zhang
- Department of Polymer Materials, Shanghai University, 99 Shangda Road, Shanghai 200444, People's Republic of China
| | - Guifei Li
- Department of Polymer Materials, Shanghai University, 99 Shangda Road, Shanghai 200444, People's Republic of China
| | - Jingbo Yin
- Department of Polymer Materials, Shanghai University, 99 Shangda Road, Shanghai 200444, People's Republic of China
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28
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Salamanna F, Maglio M, Sartori M, Tschon M, Fini M. Platelet Features and Derivatives in Osteoporosis: A Rational and Systematic Review on the Best Evidence. Int J Mol Sci 2020; 21:ijms21051762. [PMID: 32143494 PMCID: PMC7084230 DOI: 10.3390/ijms21051762] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/29/2020] [Revised: 02/27/2020] [Accepted: 03/02/2020] [Indexed: 02/06/2023] Open
Abstract
Background: With the increase in aging population, the rising prevalence of osteoporosis (OP) has become an important medical issue. Accumulating evidence showed a close relationship between OP and hematopoiesis and emerging proofs revealed that platelets (PLTs), unique blood elements, rich in growth factors (GFs), play a critical role in bone remodeling. The aim of this review was to evaluate how PLT features, size, volume, bioactive GFs released, existing GFs in PLTs and PLT derivatives change and behave during OP. Methods: A systematic search was carried out in PubMed, Scopus, Web of Science Core Collection and Cochrane Central Register of Controlled Trials databases to identify preclinical and clinical studies in the last 10 years on PLT function/features and growth factor in PLTs and on PLT derivatives during OP. The methodological quality of included studies was assessed by QUIPS tool for assessing risk of bias in the clinical studies and by the SYRCLE tool for assessing risk of bias in animal studies. Results: In the initial search, 2761 studies were obtained, only 47 articles were submitted to complete reading, and 23 articles were selected for the analysis, 13 on PLT function/features and growth factor in PLTs and 10 on PLT derivatives. Risk of bias of almost all animal studies was high, while the in the clinical studies risk of bias was prevalently moderate/low for the most of the studies. The majority of the evaluated studies highlighted a positive correlation between PLT size/volume and bone mineralization and an improvement in bone regeneration ability by using PLTs bioactive GFs and PLT derivatives. Conclusions: The application of PLT features as OP markers and of PLT-derived compounds as therapeutic approach to promote bone healing during OP need to be further confirmed to provide clear evidence for the real efficacy of these interventions and to contribute to the clinical translation.
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Alginate hydrogels for bone tissue engineering, from injectables to bioprinting: A review. Carbohydr Polym 2020; 229:115514. [DOI: 10.1016/j.carbpol.2019.115514] [Citation(s) in RCA: 199] [Impact Index Per Article: 39.8] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/16/2019] [Revised: 10/08/2019] [Accepted: 10/20/2019] [Indexed: 12/16/2022]
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Jun Y, Oh H, Karpoormath R, Jha A, Patel R. Role of microsphere as drug carrier for osteogenic differentiation. INT J POLYM MATER PO 2020. [DOI: 10.1080/00914037.2020.1713783] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Affiliation(s)
- Yuju Jun
- Department of Nano Science and Engineering, Integrated Science and Engineering Division (ISED), Underwood International College, Yonsei University, Incheon, South Korea
| | - Hyunyoung Oh
- Department of Energy and Environmental Science and Engineering, Integrated Science and Engineering Division (ISED), Underwood International College, Yonsei University, Incheon, South Korea
| | - Rajshekhar Karpoormath
- Department of Pharmaceutical Chemistry, College of Health Sciences, University of Kwa Zulu Natal, Durban, South Africa
| | - Amitabh Jha
- Department of Chemistry, Acadia University, Wolfville, Canada
| | - Rajkumar Patel
- Department of Energy and Environmental Science and Engineering, Integrated Science and Engineering Division (ISED), Underwood International College, Yonsei University, Incheon, South Korea
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Jeong W, Kim YS, Roh TS, Kang EH, Jung BK, Yun IS. The effect of combination therapy on critical-size bone defects using non-activated platelet-rich plasma and adipose-derived stem cells. Childs Nerv Syst 2020; 36:145-151. [PMID: 30879128 DOI: 10.1007/s00381-019-04109-z] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/07/2018] [Accepted: 02/27/2019] [Indexed: 02/07/2023]
Abstract
PURPOSE Non-activated platelet-rich plasma (nPRP) slowly releases growth factors that induce bone regeneration. Adipose tissue-derived stem cells (ASCs) are also known to induce osteoblast differentiation. In this study, we investigated the combined effect of nPRP and ASC treatment compared with single therapy on bone regeneration. METHODS Thirty New Zealand white rabbits with 15 × 15 mm2 calvarial defects were randomly divided into four treatment groups: control, nPRP, ASC, or nPRP + ASC groups. For treatment, rabbits received a collagen sponge (Gelfoam®) saturated with 1 ml normal saline (controls), 1 ml non-activated PRP (nPRP group), 2 × 106 ASCs (ASCs group), or 2 × 106 ASCs plus l ml nPRP (nPRP + ASCs group). After 16 weeks, bone volume and new bone surface area were measured, using three-dimensional computed tomography and digital photography. Bone regeneration was also histologically analyzed. RESULTS Bone surface area in the nPRP group was significantly higher than both the control and ASC groups (p < 0.001 and p < 0.01, respectively). The percentage of regenerated bone surface area in the nPRP + ASC group was also significantly higher than the corresponding ratios in the control group (p < 0.001). The volume of new bone in the nPRP group was increased compared to the controls (p < 0.05). CONCLUSION Our results demonstrate that slow-releasing growth factors from nPRP did not influence ASC activation in this model of bone healing. PRP activation is important for the success of combination therapy using nPRP and ASCs.
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Affiliation(s)
- Woonhyeok Jeong
- Department of Plastic and Reconstructive Surgery, Keimyung University School of Medicine, Dongsan Medical Center, Daegu, South Korea
| | - Young Seok Kim
- Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University Health System, Gangnam Severance Hospital, 211 Eonjoo-ro, Gangnam-gu, Seoul, 135-720, South Korea
| | - Tai Suk Roh
- Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University Health System, Gangnam Severance Hospital, 211 Eonjoo-ro, Gangnam-gu, Seoul, 135-720, South Korea
| | - Eun Hye Kang
- Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University Health System, Severance Hospital, Seoul, South Korea
| | - Bok Ki Jung
- Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University Health System, Gangnam Severance Hospital, 211 Eonjoo-ro, Gangnam-gu, Seoul, 135-720, South Korea
| | - In Sik Yun
- Department of Plastic and Reconstructive Surgery, Institute for Human Tissue Restoration, Yonsei University Health System, Gangnam Severance Hospital, 211 Eonjoo-ro, Gangnam-gu, Seoul, 135-720, South Korea.
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32
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Zhao Z, Liu J, Weir MD, Zhang N, Zhang L, Xie X, Zhang C, Zhang K, Bai Y, Xu HHK. Human periodontal ligament stem cells on calcium phosphate scaffold delivering platelet lysate to enhance bone regeneration. RSC Adv 2019; 9:41161-41172. [PMID: 35540034 PMCID: PMC9076431 DOI: 10.1039/c9ra08336g] [Citation(s) in RCA: 10] [Impact Index Per Article: 1.7] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/12/2019] [Accepted: 12/02/2019] [Indexed: 12/15/2022] Open
Abstract
Human periodontal ligament stem cells (hPDLSCs) are promising for tissue engineering applications but have received relatively little attention. Human platelet lysate (HPL) contains a cocktail of growth factors. To date, there has been no report on hPDLSC seeding on scaffolds loaded with HPL. The objectives of this study were to develop a calcium phosphate cement (CPC)-chitosan scaffold loaded with HPL and investigate their effects on hPDLSC viability, osteogenic differentiation and bone mineral synthesis for the first time. hPDLSCs were harvested from extracted human teeth. Scaffolds were formed by mixing CPC powder with a chitosan solution containing HPL. Four groups were tested: CPC-chitosan + 0% HPL (control); CPC-chitosan + 2.66% HPL; CPC-chitosan + 5.31% HPL; CPC-chitosan + 10.63% HPL. Scanning electron microscopy, live/dead staining, CCK-8, qRT-PCR, alkaline phosphatase and bone minerals assay were applied for hPDLSCs on scaffolds. hPDLSCs attached well on CPC-chitosan scaffold. Adding 10.63% HPL into CPC increased cell proliferation and viability (p < 0.05). ALP gene expression of CPC-chitosan + 10.63% HPL was 7-fold that of 0% HPL at 14 days. Runx2, OSX and Coll1 of CPC-chitosan + 10.63% HPL was 2-3 folds those at 0% HPL (p < 0.05). ALP activity of CPC-chitosan + 10.63% HPL was 2-fold that at 0% HPL (p < 0.05). Bone minerals synthesized by hPDLSCs for CPC-chitosan + 10.63% HPL was 3-fold that at 0% HPL (p < 0.05). This study showed that CPC-chitosan scaffold was a promising carrier for HPL delivery, and HPL in CPC exerted excellent promoting effects on hPDLSCs for bone tissue engineering for the first time. The novel hPDLSC-CPC-chitosan-HPL construct has great potential for orthopedic, dental and maxillofacial regenerative applications.
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Affiliation(s)
- Zeqing Zhao
- Department of Orthodontics, School of Stomatology, Capital Medical University Beijing China
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School Baltimore MD 21201 USA
| | - Jin Liu
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School Baltimore MD 21201 USA
- Key Laboratory of Shanxi Province for Craniofacial Precision Medicine Research, College of Stomatology, Xi'an Jiaotong University China
| | - Michael D Weir
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School Baltimore MD 21201 USA
| | - Ning Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University Beijing China
| | - Li Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University Beijing China
| | - Xianju Xie
- Department of Orthodontics, School of Stomatology, Capital Medical University Beijing China
| | - Charles Zhang
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School Baltimore MD 21201 USA
| | - Ke Zhang
- Department of Orthodontics, School of Stomatology, Capital Medical University Beijing China
| | - Yuxing Bai
- Department of Orthodontics, School of Stomatology, Capital Medical University Beijing China
| | - Hockin H K Xu
- Department of Advanced Oral Sciences and Therapeutics, University of Maryland Dental School Baltimore MD 21201 USA
- Member, Marlene and Stewart Greenebaum Cancer Center, University of Maryland School of Medicine Baltimore MD 21201 USA
- Center for Stem Cell Biology & Regenerative Medicine, University of Maryland School of Medicine Baltimore MD 21201 USA
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The Comparative Cytotoxic Effects of Apis mellifera Crude Venom on MCF-7 Breast Cancer Cell Line in 2D and 3D Cell Cultures. Int J Pept Res Ther 2019. [DOI: 10.1007/s10989-019-09979-0] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/04/2023]
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Jain E, Chinzei N, Blanco A, Case N, Sandell LJ, Sell S, Rai MF, Zustiak SP. Platelet-Rich Plasma Released From Polyethylene Glycol Hydrogels Exerts Beneficial Effects on Human Chondrocytes. J Orthop Res 2019; 37:2401-2410. [PMID: 31254416 PMCID: PMC6778705 DOI: 10.1002/jor.24404] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/25/2018] [Accepted: 06/14/2019] [Indexed: 02/04/2023]
Abstract
Osteoarthritis (OA) is a debilitating joint disease resulting from chronic joint inflammation and erosion of articular cartilage. A promising biological treatment for OA is intra-articular administration of platelet-rich plasma (PRP). However, immediate bolus release of growth factors limits beneficial therapeutic effects of PRP, thus necessitating the demand for sustained release platforms. In this study, we evaluated the therapeutic value of PRP released from a polyethylene glycol (PEG) hydrogel on articular chondrocytes/cartilage explants derived from OA patients. Lyophilized PRP (PRGF) was encapsulated in PEG hydrogels at 10% w/v and hydrogel swelling, storage modulus and degradation and PRGF release kinetics were determined. PRGF releasate from the hydrogels was collected on day 1, 4, and 11. Encapsulation of PRGF at 10% w/v in PEG hydrogels had minimal effect on hydrogel properties. PRGF was released with an initial burst followed by sustained release until complete hydrogel degradation. Effect of PRGF releasates and bolus PRGF (1% w/v PRGF) on patient-derived cartilage explants or chondrocytes was assessed by chondrocyte proliferation (pico-green assay), gene expression for COL1A1, COL2A1, MMP13, COX2, and NFKB1 (real-time polymerase chain reaction), and measurement of nitric oxide concentration (Griess' assay). Compared to bolus PRGF, PRGF releasates enhanced chondrocyte proliferation, suppressed the expression of genes like MMP13, NFKB1, COL1A1, and COL2A1 and reduced levels of nitric oxide. Taken together, these results indicate that release of PRGF from PEG hydrogels may improve the therapeutic efficacy of PRP and merits further investigation in an animal model of OA. © 2019 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 37:2401-2410, 2019.
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Affiliation(s)
- Era Jain
- Biomedical Engineering, Saint Louis University
- Department of Biomedical Engineering, Washington University
| | - Nobuaki Chinzei
- Department of Orthopedic Surgery, Musculoskeletal Research Center, Washington University
| | | | | | - Linda J Sandell
- Department of Biomedical Engineering, Washington University
- Department of Orthopedic Surgery, Musculoskeletal Research Center, Washington University
- Department of Cell Biology & Physiology, Washington University
| | - Scott Sell
- Biomedical Engineering, Saint Louis University
| | - Muhammad Farooq Rai
- Department of Orthopedic Surgery, Musculoskeletal Research Center, Washington University
- Department of Cell Biology & Physiology, Washington University
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Xie Y, Chen M, Chen Y, Xu Y, Sun Y, Liang J, Fan Y, Zhang X. Effects of PRP and LyPRP on osteogenic differentiation of MSCs. J Biomed Mater Res A 2019; 108:116-126. [PMID: 31498962 DOI: 10.1002/jbm.a.36797] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2019] [Revised: 08/28/2019] [Accepted: 09/03/2019] [Indexed: 12/13/2022]
Abstract
Platelet-rich plasma (PRP) is rich in a variety of growth factors and plays an important role in the proliferation and differentiation of mesenchymal stem cells (MSCs). It has been reported that the preparation of freeze-dried platelets (lyophilized platelets [LyPRP]) from platelets could be an effective strategy to preserve the bioactivity of platelets for a long time. In this study, the osteogenic induction effects of PRP and LyPRP on MSCs were evaluated. The rabbit arterial blood was drawing to preparation of PRP by secondary centrifugation. Whole blood was prepared by lyophilization buffer to prepare LyPRP, which were activated by chloride and their surface morphology was observed. It was observed using a scanning electron microscope that platelets were evenly distributed on the surface of PRP and LyPRP. Growth factors were slowly released from PRP and LyPRP during the first 7 days and detected by the enzyme-linked immunosorbent assay kit. Cell proliferation assays and fluoresceindiacetate/propidium iodide (FDA/PI) staining demonstrated that PRP and LyPRP could promote cell proliferation. PRP and LyPRP were also shown to promote osteogenic differentiation of MSCs in vitro by osteogenesis characteristic staining and qPCR quantitative detection of osteogenic related gene expression. Both PRP and LyPRP could promote the proliferation and osteogenic differentiation of MSCs effectively. Moreover, PRP exhibited a better osteogenic induction effect on MSC than LyPRP.
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Affiliation(s)
- Yuxing Xie
- Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, China
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Manyu Chen
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Yafang Chen
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Yang Xu
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Yong Sun
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Jie Liang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Yujiang Fan
- Guangxi Engineering Center in Biomedical Materials for Tissue and Organ Regeneration, Guangxi Collaborative Innovation Center for Biomedicine, Guangxi Medical University, Nanning, China
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
| | - Xingdong Zhang
- National Engineering Research Center for Biomaterials, Sichuan University, Chengdu, China
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36
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Fang D, Jin P, Huang Q, Yang Y, Zhao J, Zheng L. Platelet-rich plasma promotes the regeneration of cartilage engineered by mesenchymal stem cells and collagen hydrogel via the TGF-β/SMAD signaling pathway. J Cell Physiol 2019; 234:15627-15637. [PMID: 30768719 DOI: 10.1002/jcp.28211] [Citation(s) in RCA: 26] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/16/2018] [Revised: 01/12/2019] [Accepted: 01/15/2019] [Indexed: 01/24/2023]
Abstract
The tissue engineering technique using mesenchymal stem cells (MSCs) and scaffolds is promising. Transforming growth factor-β1 (TGF-β1) is generally accepted as an chondrogenic agent, but immunorejection and unexpected side effects, such as tumorigenesis and heterogeneity, limit its clinical application. Autogenous platelet-rich plasma (PRP), marked by low immunogenicity, easy accessibility, and low-cost, may be favorable for cartilage regeneration. In our study, the effect of PRP on engineered cartilage constructed by MSCs and collagen hydrogel in vitro and in vivo was investigated and compared with TGF-β1. The results showed that PRP promoted cell proliferation and gene and protein expressions of chondrogenic markers via the TGF-β/SMAD signaling pathway. Meanwhile, it suppressed the expression of collagen type I, a marker of fibrocartilage. Furthermore, PRP accelerated cartilage regeneration on defects with engineered cartilage, advantageous over TGF-β1, as evaluated by histological analysis and immunohistochemical staining. Our work demonstrates that autogenous PRP may substitute TGF-β1 as a potent and reliable chondrogenic inducer for therapy of cartilage defect.
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Affiliation(s)
- Depeng Fang
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, People's Republic of China.,Orthopaedics, Langdong Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, People's Republic of China
| | - Pan Jin
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Key Laboratory of Regenerative Medicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China
| | - Quanxin Huang
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Key Laboratory of Regenerative Medicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China
| | - Yuan Yang
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Orthopaedics, Langdong Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Key Laboratory of Regenerative Medicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China
| | - Jinmin Zhao
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Department of Orthopaedics Trauma and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Key Laboratory of Regenerative Medicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China
| | - Li Zheng
- Guangxi Engineering Center in Biomedical Material for Tissue and Organ Regeneration, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Collaborative Innovation Center for Biomedicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China.,Guangxi Key Laboratory of Regenerative Medicine, Life Sciences Institute, Guangxi Medical University, Nanning, People's Republic of China
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Hoveizi E, Tavakol S, Shirian S, Sanamiri K. Electrospun Nanofibers for Diabetes: Tissue Engineering and Cell-Based Therapies. Curr Stem Cell Res Ther 2019; 14:152-168. [PMID: 30338744 DOI: 10.2174/1574888x13666181018150107] [Citation(s) in RCA: 8] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/28/2017] [Revised: 03/11/2018] [Accepted: 09/05/2018] [Indexed: 02/08/2023]
Abstract
Diabetes mellitus is an autoimmune disease which causes loss of insulin secretion producing hyperglycemia by promoting progressive destruction of pancreatic β cells. An ideal therapeutic approach to manage diabetes mellitus is pancreatic β cells replacement. The aim of this review article was to evaluate the role of nanofibrous scaffolds and stem cells in the treatment of diabetes mellitus. Various studies have pointed out that application of electrospun biomaterials has considerably attracted researchers in the field of tissue engineering. The principles of cell therapy for diabetes have been reviewed in the first part of this article, while the usability of tissue engineering as a new therapeutic approach is discussed in the second part.
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Affiliation(s)
- Elham Hoveizi
- Department of Biology, Faculty of Science, Shahid Chamran University of Ahvaz, Ahvaz, Iran.,Stem Cells and Transgenic Technology Research Center (STTRC), Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Shima Tavakol
- Cellular and Molecular Research Center, Iran University of Medical Sciences, Tehran, Iran
| | - Sadegh Shirian
- Department of Pathology, School of Veterinary Medicine, Shahrekord University, Shahrekord, Iran.,Shiraz Molecular Research Center, Dr. Daneshbod Pathology Lab, Shiraz, Iran
| | - Khadije Sanamiri
- Department of Animal Biology, Faculty of Biological Sciences, Kharazmi University, Tehran, Iran
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Lin S, Yang G, Jiang F, Zhou M, Yin S, Tang Y, Tang T, Zhang Z, Zhang W, Jiang X. A Magnesium-Enriched 3D Culture System that Mimics the Bone Development Microenvironment for Vascularized Bone Regeneration. ADVANCED SCIENCE (WEINHEIM, BADEN-WURTTEMBERG, GERMANY) 2019; 6:1900209. [PMID: 31380166 PMCID: PMC6662069 DOI: 10.1002/advs.201900209] [Citation(s) in RCA: 98] [Impact Index Per Article: 16.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Received: 01/25/2019] [Revised: 03/20/2019] [Indexed: 05/24/2023]
Abstract
The redevelopment/regeneration pattern of amputated limbs from a blastema in salamander suggests that enhanced regeneration might be achieved by mimicking the developmental microenvironment. Inspired by the discovery that the expression of magnesium transporter-1 (MagT1), a selective magnesium (Mg) transporter, is significantly upregulated in the endochondral ossification region of mouse embryos, a Mg-enriched 3D culture system is proposed to provide an embryonic-like environment for stem cells. First, the optimum concentration of Mg ions (Mg2+) for creating the osteogenic microenvironment is screened by evaluating MagT1 expression levels, which correspond to the osteogenic differentiation capacity of stem cells. The results reveal that Mg2+ selectively activates the mitogen-activated protein kinase/extracellular regulated kinase (MAPK/ERK) pathway to stimulate osteogenic differentiation, and Mg2+ influx via MagT1 is profoundly involved in this process. Then, Mg-enriched microspheres are fabricated at the appropriate size to ensure the viability of the encapsulated cells. A series of experiments show that the Mg-enriched microenvironment not only stimulates the osteogenic differentiation of stem cells but also promotes neovascularization. Obvious vascularized bone regeneration is achieved in vivo using these Mg-enriched cell delivery vehicles. The findings suggest that biomaterials mimicking the developmental microenvironment might be promising tools to enhance tissue regeneration.
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Affiliation(s)
- Sihan Lin
- Department of ProsthodonticsShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Guangzheng Yang
- Department of ProsthodonticsShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Fei Jiang
- Department of ProsthodonticsShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Mingliang Zhou
- Department of ProsthodonticsShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Shi Yin
- Department of ProsthodonticsShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Yanmei Tang
- Department of ProsthodonticsShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Tingting Tang
- Department of Orthopaedic SurgeryNinth People's HospitalShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Zhiyuan Zhang
- Department of Oral and Maxillofacial‐Head and Neck OncologyShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Wenjie Zhang
- Department of ProsthodonticsShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
| | - Xinquan Jiang
- Department of ProsthodonticsShanghai Engineering Research Center of Advanced Dental Technology and MaterialsShanghai Research Institute of StomatologyNational Clinical Research Center for Oral DiseasesShanghai Key Laboratory of StomatologyNinth People's HospitalCollege of StomatologyShanghai JiaoTong University School of Medicine639 Zhizaoju RoadShanghai200011P. R. China
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Ramos R, Zhang K, Quinn D, Sawyer SW, Mcloughlin S, Soman P. Measuring Changes in Electrical Impedance During Cell-Mediated Mineralization. Bioelectricity 2019; 1:73-84. [PMID: 34471812 PMCID: PMC8370274 DOI: 10.1089/bioe.2018.0008] [Citation(s) in RCA: 3] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/12/2022] Open
Abstract
Background: The fundamental electrical properties of bone have been attributed to the organic collagen and the inorganic mineral component; however, contributions of individual components within bone tissue toward the measured electrical properties are not known. In our study, we investigated the electrical properties of cell-mediated mineral deposition process and compared our results with cell-free mineralization. Materials and Methods: Saos-2 cells encapsulated within gelatin methacrylate (GelMA) hydrogels were chemically stimulated in osteogenic medium for a period of 4 weeks. The morphology, composition, and mechanical properties of the mineralized constructs were characterized using bright-field imaging, scanning electron microscopy (SEM) energy-dispersive X-ray spectroscopy, Fourier-transform infrared spectroscopy (FITR), nuclear magnetic resonance spectroscopy (NMR), micro-CT, immunostaining, and mechanical compression tests. In parallel, a custom-made device was used to measure the electrical impedance of mineralized constructs. All results were compared with cell-free GelMA hydrogels mineralized through the simulated body fluid approach. Results: Results demonstrate a decrease in the electrical impedance of deposited mineral in both cell-mineralized and cell-free mineralized samples. Conclusions: This study establishes a model system to investigate in vivo and in vitro mineralization processes.
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Affiliation(s)
- Rafael Ramos
- Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York
- Syracuse Biomaterial Institute, Syracuse, New York
| | - Kairui Zhang
- Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York
- Syracuse Biomaterial Institute, Syracuse, New York
| | - David Quinn
- Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York
- Syracuse Biomaterial Institute, Syracuse, New York
| | - Stephen W. Sawyer
- Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York
- Syracuse Biomaterial Institute, Syracuse, New York
| | - Shannon Mcloughlin
- Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York
- Syracuse Biomaterial Institute, Syracuse, New York
| | - Pranav Soman
- Department of Biomedical and Chemical Engineering, Syracuse University, Syracuse, New York
- Syracuse Biomaterial Institute, Syracuse, New York
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40
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Vertical Bone Construction with Bone Marrow-Derived and Adipose Tissue-Derived Stem Cells. Symmetry (Basel) 2019. [DOI: 10.3390/sym11010059] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/25/2023] Open
Abstract
The purpose of this study was to conduct a histomorphometric analysis of bone marrow-derived and adipose tissue-derived stem cells, associated with a xenograft block, in vertical bone constructions in rabbit calvaria. Ten rabbits received two xenograft blocks on the calvaria, after decortication of the parietal bone. The blocks were fixed with titanium screws. The blocks were combined with the bone marrow-derived mesenchymal stem cells in the bone marrow stem cell (BMSC) group (right side of the calvaria) or with the adipose tissue-derived mesenchymal stem cells in the adipose tissue stem cell (ATSC) group (left side of the calvaria). After 8 weeks, the animals were sacrificed and their parietal bones were fixed in 10% formalin for the histomorphometric analysis. The following parameters were evaluated—newly formed bone (NFB), xenogeneic residual particles (XRP), and non-mineralized tissue (NMT). The histomorphometric analysis revealed 11.9 ± 7.5% and 7.6 ± 5.6% for NFB, 22.14 ± 8.5% and 21.6 ± 8.5% for XRP, and 65.8 ± 10.4% and 70.8 ± 7.4% for NMT in groups BMSC and ATSC, respectively, with statistically significant differences in the NFB and the NMT between the groups, but no differences in the XRP. Therefore, it can be concluded that the bone marrow-derived stem cells seem to have more potential for the bone formation than do the adipose tissue-derived stem cells when used in combination with the xenogenous blocks in the vertical bone construction.
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Xie M, Gao Q, Zhao H, Nie J, Fu Z, Wang H, Chen L, Shao L, Fu J, Chen Z, He Y. Electro-Assisted Bioprinting of Low-Concentration GelMA Microdroplets. SMALL (WEINHEIM AN DER BERGSTRASSE, GERMANY) 2019; 15:e1804216. [PMID: 30569632 DOI: 10.1002/smll.201804216] [Citation(s) in RCA: 73] [Impact Index Per Article: 12.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 10/11/2018] [Revised: 11/16/2018] [Indexed: 05/18/2023]
Abstract
Low-concentration gelatin methacryloyl (GelMA) has excellent biocompatibility to cell-laden structures. However, it is still a big challenge to stably fabricate organoids (even microdroplets) using this material due to its extremely low viscosity. Here, a promising electro-assisted bioprinting method is developed, which can print low-concentration pure GelMA microdroplets with low cost, low cell damage, and high efficiency. With the help of electrostatic attraction, uniform GelMA microdroplets measuring about 100 μm are rapidly printed. Due to the application of lower external forces to separate the droplets, cell damage during printing is negligible, which often happens in piezoelectric or thermal inkjet bioprinting. Different printing states and effects of printing parameters (voltages, gas pressure, nozzle size, etc.) on microdroplet diameter are also investigated. The fundamental properties of low-concentration GelMA microspheres are subsequently studied. The results show that the printed microspheres with 5% w/v GelMA can provide a suitable microenvironment for laden bone marrow stem cells. Finally, it is demonstrated that the printed microdroplets can be used in building microspheroidal organoids, in drug controlled release, and in 3D bioprinting as biobricks. This method shows great potential use in cell therapy, drug delivery, and organoid building.
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Affiliation(s)
- Mingjun Xie
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Qing Gao
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Haiming Zhao
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Jing Nie
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Zhenliang Fu
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Haoxuan Wang
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Lulu Chen
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Lei Shao
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Jianzhong Fu
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Zichen Chen
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
| | - Yong He
- State Key Laboratory of Fluid Power and Mechatronic Systems, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
- Key Laboratory of 3D Printing Process and Equipment of Zhejiang Province, School of Mechanical Engineering, Zhejiang University, Hangzhou, 310027, China
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Chen R, Sun Z, Chen D. Droplet-based microfluidics for cell encapsulation and delivery. MICROFLUIDICS FOR PHARMACEUTICAL APPLICATIONS 2019:307-335. [DOI: 10.1016/b978-0-12-812659-2.00011-9] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/06/2025]
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43
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Wu R, Ruan J, Sun Y, Liu M, Sha Z, Fan C, Wu Q. Long non-coding RNA HIF1A-AS2 facilitates adipose-derived stem cells (ASCs) osteogenic differentiation through miR-665/IL6 axis via PI3K/Akt signaling pathway. Stem Cell Res Ther 2018; 9:348. [PMID: 30545407 PMCID: PMC6293597 DOI: 10.1186/s13287-018-1082-z] [Citation(s) in RCA: 43] [Impact Index Per Article: 6.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/15/2018] [Revised: 10/10/2018] [Accepted: 11/19/2018] [Indexed: 12/12/2022] Open
Abstract
Background This study was aimed to investigate the role and specific molecular mechanism of HIF1A-AS2/miR-665/IL6 axis in regulating osteogenic differentiation of adipose-derived stem cells (ASCs) via the PI3K/Akt signaling pathway. Methods RNAs’ expression profile in normal/osteogenic differentiation-induced ASCs (osteogenic group) was from the Gene Expression Omnibus database. The analysis was carried out using Bioconductor of R. Gene Set Enrichment Analysis and Kyoto Encyclopedia of Genes and Genomes dataset were applied to identify up- and downregulated signaling pathways. Co-expression network of specific lncRNAs and mRNAs was structured by Cytoscape, while binding sites amongst lncRNA, mRNA, and miRNA were predicted by TargetScan and miRanda. ASCs were derived from human adipose tissue and were authenticated by flow cytometry. ASC cell function was surveyed by alizarin red and alkaline phosphatase (ALP) staining. Molecular mechanism of HIF1A-AS2/miR-665/IL6 axis was investigated by RNAi, cell transfection, western blot, and qRT-PCR. RNA target relationships were validated by dual-luciferase assay. Results HIF1A-AS2 and IL6 were highly expressed while miR-665 was lowly expressed in induced ASCs. HIF1A-AS2 and IL6 improved the expression level of osteoblast markers Runx2, Osterix, and Osteocalcin and also accelerated the formation of calcium nodule and ALP activity, yet miR-665 had opposite effects. HIF1A-AS2 directly targeted miR-665, whereas miR-665 repressed IL6 expression. Moreover, the HIF1A-AS2/miR-665/IL6 regulating axis activated the PI3K/Akt signaling pathway. Conclusions LncRNA HIF1A-AS2 could sponge miR-665 and hence upregulate IL6, activate the PI3K/Akt signaling pathway, and ultimately promote ASC osteogenic differentiation. Electronic supplementary material The online version of this article (10.1186/s13287-018-1082-z) contains supplementary material, which is available to authorized users.
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Affiliation(s)
- Ruoyu Wu
- Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Jihao Ruan
- Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600 Yishan Road, Xuhui District, Shanghai, 200233, China
| | - Yongjin Sun
- Institute of Microsurgery on Extremities, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Mengyu Liu
- Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China
| | - Zhuang Sha
- Institute of Nervous System Diseases, Xuzhou Medical University, Xuzhou, 221004, Jiangsu, China
| | - Cunyi Fan
- Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600 Yishan Road, Xuhui District, Shanghai, 200233, China.
| | - Qingkai Wu
- Department of Orthopaedics, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, No.600 Yishan Road, Xuhui District, Shanghai, 200233, China. .,Department of Obstetrics and Gynecology, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai, 200233, China.
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44
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Lalegül-Ülker Ö, Şeker Ş, Elçin AE, Elçin YM. Encapsulation of bone marrow-MSCs in PRP-derived fibrin microbeads and preliminary evaluation in a volumetric muscle loss injury rat model: modular muscle tissue engineering. ARTIFICIAL CELLS NANOMEDICINE AND BIOTECHNOLOGY 2018; 47:10-21. [PMID: 30514127 DOI: 10.1080/21691401.2018.1540426] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/31/2022]
Abstract
Repair of volumetric muscle loss (VML) injuries is a complicated endeavour which necessitates the collaborative use of different regenerative approaches and technologies. Herein is proposed the development of fibrin-based microbeads (FMs) alone or as a bone marrow mesenchymal stem cell (MSC) encapsulation matrix for modular muscle engineering. FMs were generated through the ionotropic gelation of alginate and fibrinogen obtained from the platelet-rich plasma of whole blood, and then removing the alginate by citrate treatment. FMs were first characterized by FT-IR, SEM and water uptake tests. Then, the stability of FMs and the mitochondrial dehydrogenase activity of the MSCs encapsulated in FMs were evaluated under in vitro culture conditions. Eventually, the regenerative capacity of the cell-devoid and MSCs-encapsulated FMs was evaluated in a rat VML injury model involving 8 × 4×4 mm3-size bilateral defects in the biceps femoris muscles. The histochemical, immunohistochemical and semi-quantitative histomorphological scoring results retrieved at 30, 60 and 180 days demonstrated that the cell-devoid FMs supported muscle regeneration to a great extent. Moreover, MSCs-encapsulated FMs were more effective in shortening the regeneration period of the injured tissue of the rat VML, resulting in good myofibre orientation, while the Sham group resulted in incomplete repair with fibrotic scar tissue formations.
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Affiliation(s)
- Özge Lalegül-Ülker
- a Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory , Ankara University Faculty of Science, and Ankara University Stem Cell Institute , Ankara , Turkey
| | - Şükran Şeker
- a Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory , Ankara University Faculty of Science, and Ankara University Stem Cell Institute , Ankara , Turkey
| | - Ayşe Eser Elçin
- a Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory , Ankara University Faculty of Science, and Ankara University Stem Cell Institute , Ankara , Turkey
| | - Yaşar Murat Elçin
- a Tissue Engineering, Biomaterials and Nanobiotechnology Laboratory , Ankara University Faculty of Science, and Ankara University Stem Cell Institute , Ankara , Turkey.,b Biovalda Health Technologies, Inc. , Ankara , Turkey
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45
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Smith OJ, Jell G, Mosahebi A. The use of fat grafting and platelet-rich plasma for wound healing: A review of the current evidence. Int Wound J 2018; 16:275-285. [PMID: 30460739 DOI: 10.1111/iwj.13029] [Citation(s) in RCA: 40] [Impact Index Per Article: 5.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/22/2018] [Accepted: 10/16/2018] [Indexed: 12/17/2022] Open
Abstract
Fat grafting is becoming a common procedure in regenerative medicine because of its high content of growth factors and adipose derived stem cells (ADSCs) and the ease of harvest, safety, and low cost. The high concentration of ADSCs found in fat has the potential to differentiate into a wide range of wound-healing cells including fibroblasts and keratinocytes as well as demonstrating proangiogenic qualities. This suggests that fat could play an important role in wound healing. However retention rates of fat grafts are highly variable due in part to inconsistent vascularisation of the transplanted fat. Furthermore, conditions such as diabetes, which have a high prevalence of chronic wounds, reduce the potency and regenerative potential of ADSCs. Platelet-rich plasma (PRP) is an autologous blood product rich in growth factors, cell adhesion molecules, and cytokines. It has been hypothesised that PRP may have a positive effect on the survival and retention of fat grafts because of improved proliferation and differentiations of ADSCs, reduced inflammation, and improved vascularisation. There is also increasing interest in a possible synergistic effect that PRP may have on the healing potential of fat, although the evidence for this is very limited. In this review, we evaluate the evidence in both in vitro and animal studies on the mechanistic relationship between fat and PRP and how this translates to a benefit in wound healing. We also discuss future directions for both research and clinical practice on how to enhance the regenerative potential of the combination of PRP and fat.
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Affiliation(s)
- Oliver J Smith
- Department of Plastic Surgery, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
| | - Gavin Jell
- Division of Surgery and Interventional Science, University College London, London, UK
| | - Ash Mosahebi
- Department of Plastic Surgery, Royal Free Hospital, London, UK.,Division of Surgery and Interventional Science, University College London, London, UK
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46
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Kiaie N, Aghdam RM, Tafti SHA, Gorabi AM. Stem Cell-Mediated Angiogenesis in Tissue Engineering Constructs. Curr Stem Cell Res Ther 2018; 14:249-258. [PMID: 30394215 DOI: 10.2174/1574888x13666181105145144] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/04/2018] [Revised: 10/09/2018] [Accepted: 10/31/2018] [Indexed: 11/22/2022]
Abstract
Angiogenesis has always been a concern in the field of tissue engineering. Poor vascularization of engineered constructs is a problem for the clinical success of these structures. Among the various methods employed to induce angiogenesis, stem cells provide a promising tool for the future. The present review aims to present the application of stem cells in the induction of angiogenesis. Additionally, it summarizes recent advancements in stem cell-mediated angiogenesis of different tissue engineering constructs.
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Affiliation(s)
- Nasim Kiaie
- School of Metallurgy & Materials Engineering, College of Engineering, University of Tehran, Tehran, Iran.,Department of Tissue Engineering, Amirkabir University of Technology, Tehran 15875, Iran
| | - Rouhollah M Aghdam
- School of Metallurgy & Materials Engineering, College of Engineering, University of Tehran, Tehran, Iran
| | - Seyed H Ahmadi Tafti
- Research Center for Advanced Technologies in Cardiovascular Medicine, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
| | - Armita M Gorabi
- Department of Basic and Clinical Research, Tehran Heart Center, Tehran University of Medical Sciences, Tehran, Iran
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47
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Campbell KT, Stilhano RS, Silva EA. Enzymatically degradable alginate hydrogel systems to deliver endothelial progenitor cells for potential revasculature applications. Biomaterials 2018; 179:109-121. [PMID: 29980073 PMCID: PMC6746553 DOI: 10.1016/j.biomaterials.2018.06.038] [Citation(s) in RCA: 58] [Impact Index Per Article: 8.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/05/2018] [Revised: 06/13/2018] [Accepted: 06/24/2018] [Indexed: 12/11/2022]
Abstract
The objective of this study was to design an injectable biomaterial system that becomes porous in situ to deliver and control vascular progenitor cell release. Alginate hydrogels were loaded with outgrowth endothelial cells (OECs) and alginate lyase, an enzyme which cleaves alginate polymer chains. We postulated and confirmed that higher alginate lyase concentrations mediated loss of hydrogel mechanical properties. Hydrogels incorporating 5 and 50 mU/mL of alginate lyase experienced approximately 28% and 57% loss of mass as well as 81% and 91% reduction in storage modulus respectively after a week. Additionally, computational methods and mechanical analysis revealed that hydrogels with alginate lyase significantly increased in mesh size over time. Furthermore, alginate lyase was not found to inhibit OEC proliferation, viability or sprouting potential. Finally, alginate hydrogels incorporating OECs and alginate lyase promoted up to nearly a 10 fold increase in OEC migration in vitro than nondegradable hydrogels over the course of a week and increased functional vasculature in vivo via a chick chorioallantoic membrane (CAM) assay. Overall, these findings demonstrate that alginate lyase incorporated hydrogels can provide a simple and robust system to promote controlled outward cell migration into native tissue for potential therapeutic revascularization applications.
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Affiliation(s)
- Kevin T Campbell
- Department of Biomedical Engineering, University of California Davis, Davis, CA, USA
| | - Roberta S Stilhano
- Department of Biomedical Engineering, University of California Davis, Davis, CA, USA; Department of Biochemistry, University of Sao Paulo, Sao Paulo, Brazil
| | - Eduardo A Silva
- Department of Biomedical Engineering, University of California Davis, Davis, CA, USA.
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Whitely M, Cereceres S, Dhavalikar P, Salhadar K, Wilems T, Smith B, Mikos A, Cosgriff-Hernandez E. Improved in situ seeding of 3D printed scaffolds using cell-releasing hydrogels. Biomaterials 2018; 185:194-204. [PMID: 30245387 DOI: 10.1016/j.biomaterials.2018.09.027] [Citation(s) in RCA: 46] [Impact Index Per Article: 6.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2018] [Revised: 09/11/2018] [Accepted: 09/16/2018] [Indexed: 12/31/2022]
Abstract
The design of tissue engineered scaffolds based on polymerized high internal phase emulsions (polyHIPEs) has emerged as a promising bone grafting strategy. We previously reported the ability to 3D print emulsion inks to better mimic the structure and mechanical properties of native bone while precisely matching defect geometry. In the current study, redox-initiated hydrogel carriers were investigated for in situ delivery of human mesenchymal stem cells (hMSCs) utilizing the biodegradable macromer, poly(ethylene glycol)-dithiothreitol. Hydrogel carrier properties including network formation time, sol-gel fraction, and swelling ratio were modulated to achieve rapid cure without external stimuli and a target cell-release period of 5-7 days. These in situ carriers enabled improved distribution of hMSCs in 3D printed polyHIPE grafts over standard suspension seeding. Additionally, carrier-loaded polyHIPEs supported sustained cell viability and osteogenic differentiation of hMSCs post-release. In summary, these findings demonstrate the potential of this in situ curing hydrogel carrier to enhance the cell distribution and retention of hMSCs in bone grafts. Although initially focused on improving bone regeneration, the ability to encapsulate cells in a hydrogel carrier without relying on external stimuli that can be attenuated in large grafts or tissues is expected to have a wide range of applications in tissue engineering.
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Affiliation(s)
- Michael Whitely
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843-3120, USA.
| | - Stacy Cereceres
- Department of Biomedical Engineering, Texas A&M University, College Station, TX, 77843-3120, USA.
| | - Prachi Dhavalikar
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
| | - Karim Salhadar
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
| | - Thomas Wilems
- Department of Biomedical Engineering, University of Texas at Austin, Austin, TX, 78712, USA.
| | - Brandon Smith
- Department of Bioengineering, Rice University, Houston, TX, 77005, USA.
| | - Antonios Mikos
- Department of Bioengineering, Rice University, Houston, TX, 77005, USA.
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Hou Y, Xie W, Achazi K, Cuellar-Camacho JL, Melzig MF, Chen W, Haag R. Injectable degradable PVA microgels prepared by microfluidic technology for controlled osteogenic differentiation of mesenchymal stem cells. Acta Biomater 2018; 77:28-37. [PMID: 29981495 DOI: 10.1016/j.actbio.2018.07.003] [Citation(s) in RCA: 73] [Impact Index Per Article: 10.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/21/2018] [Revised: 05/23/2018] [Accepted: 07/02/2018] [Indexed: 12/25/2022]
Abstract
The direct injection of bone marrow mesenchymal stem cells (hMSCs) is a promising strategy for bone tissue engineering applications. Herein, we have developed injectable degradable poly(vinyl alcohol) (PVA) microgels loaded with hMSCs and growth factors and prepared by a high-throughput microfluidic technology. The PVA-based microgels with tunable mechanical and degradable properties were composed of vinyl ether acrylate-functionalized PVA (PVA-VEA) and thiolated PVA-VEA (PVA-VEA-SH) through a Michael-type crosslinking reaction under mild conditions. The hMSCs sustain high viability in PVA microgels, and cell proliferation and migration behaviors can easily be adjusted by varying crosslinking densities of PVA microgels. Additionally, bone morphogenetic protein-2 (BMP-2) co-encapsulated into the microgel environments enhanced osteogenic differentiation of hMSCs as indicated by a significant increase in alkaline phosphatase activity, calcium content, and Runx2 and OPN gene expression levels. These results demonstrate the degradable PVA microgels with tailored stem cell microenvironments and controlled release profile of the growth factor to promote and direct differentiation. These PVA-based microgels have promising potential as ideal cell vehicles for applications in regenerative medicine. STATEMENT OF SIGNIFICANCE Stem cell transplantation by an injectable, minimally invasive method has great and promising potential for various injuries, diseases, and tissue regeneration. However, its applications are largely limited owing to the low cell retention and engraftment at the lesion location after administration. We have developed an injectable degradable poly(vinyl alcohol) (PVA) microgel prepared by a high-throughput microfluidic technology and co-loaded with bone marrow mesenchymal stem cells (hMSCs) and growth factor to protect the stem cells from harsh environmental stress and realize controlled cell differentiation in well-defined microenvironments for bone regeneration. We demonstrated that these degradable PVA microgels can be used as stem cell scaffolds with tailored cell microenvironments and controlled release profile of growth factor to promote and direct differentiation. We are convinced that these PVA-based microgels have promising potential in the future as cellular scaffolds for applications in regenerative medicine.
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Affiliation(s)
- Yong Hou
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany
| | - Wenyan Xie
- Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Stasse 2-4, 14195 Berlin, Germany
| | - Katharina Achazi
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany
| | - Jose Luis Cuellar-Camacho
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany
| | - Matthias F Melzig
- Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Stasse 2-4, 14195 Berlin, Germany
| | - Wei Chen
- Department of Pharmaceutical Engineering, School of Engineering, China Pharmaceutical University, Nanjing 210009, PR China.
| | - Rainer Haag
- Institute of Chemistry and Biochemistry, Freie Universität Berlin, Takustrasse 3, Berlin 14195, Germany.
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50
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DURUKSU G, POLAT S, KAYİŞ L, EKİMCİ GÜRCAN N, GACAR G, YAZIR Y. Improvement of the insulin secretion from beta cells encapsulated in alginate/poly-L- histidine/alginate microbeads by platelet-rich plasma. Turk J Biol 2018; 42:297-306. [PMID: 30814893 PMCID: PMC6392160 DOI: 10.3906/biy-1802-13] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
Type 1 diabetes is clinically characterized as the loss of control of glucose homeostasis due to the reduced number of insulinproducing cells. Long-term glycemic control after implantation could be maintained by preserving the cell viability and tissue-specific functions during the process of microencapsulation. In this study, alginate solution was supplemented with platelet-rich plasma (PRP) to improve the viability and preserve the cell functions during the encapsulation of a beta cell line (BRIN-BD11). Cell viability was assessed and insulin secretion and insulin stimulation index were evaluated. eTh polymerization of alginate with PRP enhanced the viability up to 61% in the alginate microbeads. PRP supplementation to the alginate composition not only increased the number of viable cells by 1.95-fold, but the insulin secretion also improved by about 66%. eTh stimulation index, however, was not affected by the PRP supplementation.
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Affiliation(s)
- Gökhan DURUKSU
- Center for Stem Cell and Gene eThrapies Research and Practice, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
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İzmit, Kocaeli
,
Turkey
| | - Selen POLAT
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Leyla KAYİŞ
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Nur EKİMCİ GÜRCAN
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Gülçin GACAR
- Center for Stem Cell and Gene eThrapies Research and Practice, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| | - Yusufhan YAZIR
- Center for Stem Cell and Gene eThrapies Research and Practice, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
- Department of Histology and Embryology, School of Medicine, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
- Department of Stem Cells, Institute of Health Sciences, Kocaeli University
,
İzmit, Kocaeli
,
Turkey
| |
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