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1
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Mao R, Zhang J, Qin H, Liu Y, Xing Y, Zeng W. Application progress of bio-manufacturing technology in kidney organoids. Biofabrication 2025; 17:022007. [PMID: 39933190 DOI: 10.1088/1758-5090/adb4a1] [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: 08/04/2024] [Accepted: 02/11/2025] [Indexed: 02/13/2025]
Abstract
Kidney transplantation remains a pivotal treatment modality for kidney disease, yet its progress is significantly hindered by the scarcity of donor kidneys and ethical dilemmas surrounding their procurement. As organoid technology evolves and matures, the creation of bionic human kidney organoids offers profound potential for advancing kidney disease research, drug nephrotoxicity screening, and regenerative medicine. Nevertheless, current kidney organoid models grapple with limitations such as constrained cellular differentiation, underdeveloped functional structures, and a crucial absence of vascularization. This deficiency in vascularization, in particular, stunts organoid development, restricts their size, diminishes filtration capabilities, and may trigger immune inflammatory reactions through the resulting ischemic microenvironment. Hence, the achievement of vascularization within kidney organoids and the successful establishment of functional microvascular networks constitutes a paramount goal for their future progression. In this review, we provide an overview of recent advancements in biotechnology domains, encompassing organ-on-a-chip technology, biomimetic matrices, and bioprinting, with the aim of catalyzing technological breakthroughs that can enhance the vascularization of kidney organoids and broaden their applicability. These technologies hold the key to unlocking the full potential of kidney organoids as a transformative therapeutic option for kidney disease.
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Affiliation(s)
- Runqi Mao
- Department of Cell Biology, Third Military Medical University, Chongqing, People's Republic of China
| | - Junming Zhang
- Department of Cell Biology, Third Military Medical University, Chongqing, People's Republic of China
| | - Haoxiang Qin
- Department of Cell Biology, Third Military Medical University, Chongqing, People's Republic of China
| | - Yuanyuan Liu
- Department of Cell Biology, Third Military Medical University, Chongqing, People's Republic of China
| | - Yuxin Xing
- Department of Cell Biology, Third Military Medical University, Chongqing, People's Republic of China
| | - Wen Zeng
- Department of Cell Biology, Third Military Medical University, Chongqing, People's Republic of China
- State Key Laboratory of Trauma, Burn and Combined Injury, Chongqing, People's Republic of China
- Jinfeng Laboratory, Chongqing 401329, People's Republic of China
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2
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Raoufinia R, Arabnezhad A, Keyhanvar N, Abdyazdani N, Saburi E, Naseri N, Niazi F, Niazi F, Namdar AB, Rahimi HR. Leveraging stem cells to combat hepatitis: a comprehensive review of recent studies. Mol Biol Rep 2024; 51:459. [PMID: 38551743 DOI: 10.1007/s11033-024-09391-y] [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: 10/08/2023] [Accepted: 02/27/2024] [Indexed: 04/02/2024]
Abstract
Hepatitis is a significant global public health concern, with viral infections being the most common cause of liver inflammation. Antiviral medications are the primary treatments used to suppress the virus and prevent liver damage. However, the high cost of these drugs and the lack of awareness and stigma surrounding the disease create challenges in managing hepatitis. Stem cell therapy has arisen as a promising therapeutic strategy for hepatitis by virtue of its regenerative and immunomodulatory characteristics. Stem cells have the exceptional capacity to develop into numerous cell types and facilitate tissue regeneration, rendering them a highly promising therapeutic avenue for hepatitis. In animal models, stem cell therapy has demonstrated worthy results by reducing liver inflammation and improving liver function. Furthermore, clinical trials have been undertaken to assess the safety and effectiveness of stem cell therapy in individuals with hepatitis. This review aims to explore the involvement of stem cells in treating hepatitis and highlight the findings from studies conducted on both animals and humans. The objective of this review is to primarily concentrate on the ongoing and future clinical trials that assess the application of stem cell therapy in the context of hepatitis, including the transplantation of autologous bone marrow-derived stem cells, human induced pluripotent stem cells, and other mesenchymal stem cells. In addition, this review will explore the potential merits and constraints linked to stem cell therapy for hepatitis, as well as its prospective implications in the management of this disease.
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Affiliation(s)
- Ramin Raoufinia
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
- Department of Basic Medical Sciences, Neyshabur University of Medical Sciences, Neyshabur, Iran
| | - Ali Arabnezhad
- Department of Pharmacognosy, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Neda Keyhanvar
- Department of Biochemistry & Biophysics, University of California San Francisco, San Francisco, CA, 94107, USA
| | - Nima Abdyazdani
- Stem Cell Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
| | - Ehsan Saburi
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Nima Naseri
- Department of Biochemistry, School of medicine, Hamadan University of medical sciences, Hamadan, Iran
| | - Fereshteh Niazi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Faezeh Niazi
- Student Research Committee, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Ali Beheshti Namdar
- Department of Gastroenterology and Hepatology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran
| | - Hamid Reza Rahimi
- Department of Medical Genetics and Molecular Medicine, School of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.
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3
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Malektaj H, Nour S, Imani R, Siadati MH. Angiogenesis induction as a key step in cardiac tissue Regeneration: From angiogenic agents to biomaterials. Int J Pharm 2023; 643:123233. [PMID: 37460050 DOI: 10.1016/j.ijpharm.2023.123233] [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: 01/25/2023] [Revised: 07/02/2023] [Accepted: 07/14/2023] [Indexed: 07/23/2023]
Abstract
Cardiovascular diseases are the leading cause of death worldwide. After myocardial infarction, the vascular supply of the heart is damaged or blocked, leading to the formation of scar tissue, followed by several cardiac dysfunctions or even death. In this regard, induction of angiogenesis is considered as a vital process for supplying nutrients and oxygen to the cells in cardiac tissue engineering. The current review aims to summarize different approaches of angiogenesis induction for effective cardiac tissue repair. Accordingly, a comprehensive classification of induction of pro-angiogenic signaling pathways through using engineered biomaterials, drugs, angiogenic factors, as well as combinatorial approaches is introduced as a potential platform for cardiac regeneration application. The angiogenic induction for cardiac repair can enhance patient treatment outcomes and generate economic prospects for the biomedical industry. The development and commercialization of angiogenesis methods often involves collaboration between academic institutions, research organizations, and biomedical companies.
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Affiliation(s)
- Haniyeh Malektaj
- Department of Materials and Production, Aalborg University, Fibigerstraede 16, Aalborg 9220, Denmark
| | - Shirin Nour
- Department of Biomedical Engineering, Graeme Clark Institute, The University of Melbourne, VIC 3010, Australia; Department of Chemical Engineering, The University of Melbourne, VIC 3010, Australia
| | - Rana Imani
- Department of Biomedical Engineering, Amirkabir University of Technology, Tehran, Iran.
| | - Mohammad H Siadati
- Materials Science and Engineering Faculty, K. N. Toosi University of Technology, Tehran, Iran
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4
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Nicosia A, Salamone M, Costa S, Ragusa MA, Ghersi G. Mimicking Molecular Pathways in the Design of Smart Hydrogels for the Design of Vascularized Engineered Tissues. Int J Mol Sci 2023; 24:12314. [PMID: 37569691 PMCID: PMC10418696 DOI: 10.3390/ijms241512314] [Citation(s) in RCA: 2] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/07/2023] [Revised: 07/21/2023] [Accepted: 07/31/2023] [Indexed: 08/13/2023] Open
Abstract
Biomaterials are pivotal in supporting and guiding vascularization for therapeutic applications. To design effective, bioactive biomaterials, understanding the cellular and molecular processes involved in angiogenesis and vasculogenesis is crucial. Biomaterial platforms can replicate the interactions between cells, the ECM, and the signaling molecules that trigger blood vessel formation. Hydrogels, with their soft and hydrated properties resembling natural tissues, are widely utilized; particularly synthetic hydrogels, known for their bio-inertness and precise control over cell-material interactions, are utilized. Naturally derived and synthetic hydrogel bases are tailored with specific mechanical properties, controlled for biodegradation, and enhanced for cell adhesion, appropriate biochemical signaling, and architectural features that facilitate the assembly and tubulogenesis of vascular cells. This comprehensive review showcases the latest advancements in hydrogel materials and innovative design modifications aimed at effectively guiding and supporting vascularization processes. Furthermore, by leveraging this knowledge, researchers can advance biomaterial design, which will enable precise support and guidance of vascularization processes and ultimately enhance tissue functionality and therapeutic outcomes.
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Affiliation(s)
- Aldo Nicosia
- Institute for Biomedical Research and Innovation-National Research Council (IRIB-CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy;
| | - Monica Salamone
- Institute for Biomedical Research and Innovation-National Research Council (IRIB-CNR), Via Ugo la Malfa 153, 90146 Palermo, Italy;
| | - Salvatore Costa
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy; (S.C.); (M.A.R.); (G.G.)
| | - Maria Antonietta Ragusa
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy; (S.C.); (M.A.R.); (G.G.)
| | - Giulio Ghersi
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, Ed. 16, 90128 Palermo, Italy; (S.C.); (M.A.R.); (G.G.)
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5
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Mir A, Lee E, Shih W, Koljaka S, Wang A, Jorgensen C, Hurr R, Dave A, Sudheendra K, Hibino N. 3D Bioprinting for Vascularization. Bioengineering (Basel) 2023; 10:bioengineering10050606. [PMID: 37237676 DOI: 10.3390/bioengineering10050606] [Citation(s) in RCA: 12] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/05/2023] [Revised: 04/27/2023] [Accepted: 05/07/2023] [Indexed: 05/28/2023] Open
Abstract
In the world of clinic treatments, 3D-printed tissue constructs have emerged as a less invasive treatment method for various ailments. Printing processes, scaffold and scaffold free materials, cells used, and imaging for analysis are all factors that must be observed in order to develop successful 3D tissue constructs for clinical applications. However, current research in 3D bioprinting model development lacks diverse methods of successful vascularization as a result of issues with scaling, size, and variations in printing method. This study analyzes the methods of printing, bioinks used, and analysis techniques in 3D bioprinting for vascularization. These methods are discussed and evaluated to determine the most optimal strategies of 3D bioprinting for successful vascularization. Integrating stem and endothelial cells in prints, selecting the type of bioink according to its physical properties, and choosing a printing method according to physical properties of the desired printed tissue are steps that will aid in the successful development of a bioprinted tissue and its vascularization.
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Affiliation(s)
- Amatullah Mir
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Eugenia Lee
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Wesley Shih
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Sarah Koljaka
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Anya Wang
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Caitlin Jorgensen
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Riley Hurr
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Amartya Dave
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Krupa Sudheendra
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
| | - Narutoshi Hibino
- Section of Cardiac Surgery, Department of Surgery, University of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA
- Pediatric Cardiac Surgery, Advocate Children's Hospital, 4440 W 95th St. Oak Lawn, IL 60453, USA
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6
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de Silva L, Bernal PN, Rosenberg A, Malda J, Levato R, Gawlitta D. Biofabricating the vascular tree in engineered bone tissue. Acta Biomater 2023; 156:250-268. [PMID: 36041651 DOI: 10.1016/j.actbio.2022.08.051] [Citation(s) in RCA: 19] [Impact Index Per Article: 9.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/28/2022] [Revised: 08/22/2022] [Accepted: 08/23/2022] [Indexed: 01/18/2023]
Abstract
The development of tissue engineering strategies for treatment of large bone defects has become increasingly relevant, given the growing demand for bone substitutes. Native bone is composed of a dense vascular network necessary for the regulation of bone development, regeneration and homeostasis. A major obstacle in fabricating living, clinically relevant-sized bone mimics (1-10 cm3) is the limited supply of nutrients, including oxygen to the core of the construct. Therefore, strategies to support vascularization are pivotal for the development of tissue engineered bone constructs. Creating a functional bone construct integrated with a vascular network, capable of delivering the necessary nutrients for optimal tissue development is imperative for translation into the clinics. The vascular system is composed of a complex network that runs throughout the body in a tree-like hierarchical branching fashion. A significant challenge for tissue engineering approaches lies in mimicking the intricate, multi-scale structures consisting of larger vessels (macro-vessels) which interconnect with multiple sprouting vessels (microvessels) in a closed network. The advent of biofabrication has enabled complex, out of plane channels to be generated and has laid the groundwork for the creation of multi-scale vasculature in recent years. This review highlights the key state-of-the-art achievements for the development of vascular networks of varying scales in the field of biofabrication with a particular focus for its application in developing a functional tissue engineered bone construct. STATEMENT OF SIGNIFICANCE: There is a growing need for bone substitutes to overcome the limited supply of patient-derived bone. Bone tissue engineering aims to overcome this by combining stem cells with scaffolds to restore missing bone. The current bottleneck in upscaling is the lack of an integrated vascular network, required for the delivery of nutrients to cells. 3D bioprinting techniques has enabled the creation of complex hollow structures of varying dimensions that resemble native blood vessels. The convergence of multiple materials, cell types and fabrication approaches, opens the possibility of developing clinically-relevant sized vascularized bone constructs. This review provides an up-to-date insight of the technologies currently available for the generation of complex vascular networks, with a focus on their application in bone tissue engineering.
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Affiliation(s)
- Leanne de Silva
- Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands; Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands.
| | - Paulina N Bernal
- Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands
| | - Ajw Rosenberg
- Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands
| | - Jos Malda
- Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CT, the Netherlands
| | - Riccardo Levato
- Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands; Department of Orthopaedics, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands; Department of Clinical Sciences, Faculty of Veterinary Medicine, Utrecht University, Utrecht, 3584 CT, the Netherlands
| | - Debby Gawlitta
- Department of Oral and Maxillofacial Surgery & Special Dental Care, University Medical Center Utrecht, Utrecht University, Utrecht, 3508 GA, the Netherlands; Regenerative Medicine Center Utrecht, Utrecht, 3584 CT, the Netherlands
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7
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Imam SS, Al-Abbasi FA, Hosawi S, Afzal M, Nadeem MS, Ghoneim MM, Alshehri S, Alzarea SI, Alquraini A, Gupta G, Kazmi I. Role of platelet rich plasma mediated repair and regeneration of cell in early stage of cardiac injury. Regen Ther 2022; 19:144-153. [PMID: 35229012 PMCID: PMC8856949 DOI: 10.1016/j.reth.2022.01.006] [Citation(s) in RCA: 18] [Impact Index Per Article: 6.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/21/2021] [Revised: 01/18/2022] [Accepted: 01/27/2022] [Indexed: 12/12/2022] Open
Abstract
Platelet-rich plasma (PRP) is a widely accepted treatment approach and has heightened the quality of care among physicians. PRP has been used over the last decade to boost clinical results of plastic therapies, periodontal surgery and intra-bony defects. According to certain research, elevated levels of PRP growth factors that could promote tissue repair and have the potential for PRP to be beneficial in regenerating processes that Maxillofacial and Oral Surgeons, Veterinary Officers, Athletic medicine specialists and Dermatologists have long admired. PRP is an autologous whole blood fraction that has a heavy amount of a variety of growth factors such as epidermal growth factor (EGF), Vascular Endothelial Growth Factor (VEGF), hepatocyte growth factor (HGF), fibroblast growth factors (FGFs), transforming growth factor beta-1 (TGF-b), insulin-like growth factor-I (IGF-I) and platelet-derived growth factor (PDGF) which can facilitate repair and regeneration. Moreover, a clinical trial of PRP in severe angina patients has shown its excellent safety profile. However, PRP is a very complex biological substance with an array of active biomolecules, its functions are yet to be fully clarified. In-addition, there was insufficient work assessing possible cardiovascular tissue benefits from PRP. Thus, it still remains necessary to identify the most clinically important cardiovascular applications and further research in clinical scenario need to be validated.
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Key Words
- ADMSC, adipose-derived mesenchymal stem cells
- BMSCs, bone marrow-derived mesenchymal stem cells
- Cardiac injury
- Cell repair and regeneration
- EGF, epidermal growth factor
- FDPs, fibrin degradation products
- FGFs, fibroblast growth factors
- HGF, hepatocyte growth factor
- IGF-I, insulin-like growth factor-I
- IRI, ischemic reperfusion injury
- ISO, Isoproterenol
- LP-PRP, leukocyte-poor PRP
- LR-PRP, leukocyte-rich PRP
- MH, Manuka honey
- MI, myocardial infarction
- MRI, magnetic resonance imaging
- P-PRF, pure platelet-rich fibrin
- PDGF, platelet-derived growth factor
- PRP, platelet-rich plasma
- Platelet-rich plasma
- ROS, reactive oxygen species
- TGF-b, transforming growth factor beta
- VEGF, vascular endothelial growth factor
- nsPEF, nanosecond pulsed electric fields
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Affiliation(s)
- Syed Sarim Imam
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Fahad A. Al-Abbasi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Salman Hosawi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Muhammad Afzal
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf-72341, Saudi Arabia
| | - Muhammad Shahid Nadeem
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
| | - Mohammed M. Ghoneim
- Department of Pharmacy Practice, College of Pharmacy, AlMaarefa University, Ad Diriyah 13713, Saudi Arabia
| | - Sultan Alshehri
- Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia
| | - Sami I. Alzarea
- Department of Pharmacology, College of Pharmacy, Jouf University, Sakaka, Aljouf-72341, Saudi Arabia
| | - Ali Alquraini
- Department of Pharmaceutical Chemistry, Faculty of Clinical Pharmacy, Al Baha University, Al Baha 65779, Saudi Arabia
| | - Gaurav Gupta
- Department of Pharmacology, School of Pharmacy, Suresh Gyan Vihar University, Jagatpura, Jaipur, India
- Department of Pharmacology, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, India
| | - Imran Kazmi
- Department of Biochemistry, Faculty of Science, King Abdulaziz University Jeddah 21589 Saudi Arabia
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8
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Controlled Co-delivery of pPDGF-B and pBMP-2 from intraoperatively bioprinted bone constructs improves the repair of calvarial defects in rats. Biomaterials 2022; 281:121333. [PMID: 34995904 PMCID: PMC8810707 DOI: 10.1016/j.biomaterials.2021.121333] [Citation(s) in RCA: 33] [Impact Index Per Article: 11.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/18/2021] [Revised: 12/13/2021] [Accepted: 12/24/2021] [Indexed: 02/03/2023]
Abstract
Intraoperative bioprinting (IOB), which refers to the bioprinting process performed on a live subject in a surgical setting, has made it feasible to directly deliver gene-activated matrices into craniomaxillofacial (CMF) defect sites. In this study, we demonstrated a novel approach to overcome the current limitations of traditionally fabricated non-viral gene delivery systems through direct IOB of bone constructs into defect sites. We used a controlled co-delivery release of growth factors from a gene-activated matrix (an osteogenic bioink loaded with plasmid-DNAs (pDNA)) to promote bone repair. The controlled co-delivery approach was achieved from the combination of platelet-derived growth factor-B encoded plasmid-DNA (pPDGF-B) and chitosan-nanoparticle encapsulating pDNA encoded with bone morphogenetic protein-2 (CS-NPs(pBMP2)), which facilitated a burst release of pPDGF-B in 10 days, and a sustained release of pBMP-2 for 5 weeks in vitro. The controlled co-delivery approach was tested for its potential to repair critical-sized rat calvarial defects. The controlled-released pDNAs from the intraoperatively bioprinted bone constructs resulted in ∼40% bone tissue formation and ∼90% bone coverage area at 6 weeks compared to ∼10% new bone tissue and ∼25% total bone coverage area in empty defects. The delivery of growth factors incorporated within the intraoperatively bioprinted constructs could pose as an effective way to enhance bone regeneration in patients with cranial injuries in the future.
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9
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Van Eps JL, Boada C, Scherba JC, Zavlin D, Arrighetti N, Shi A, Wang X, Tasciotti E, Buell JF, Ellsworth WA, Bonville DJ, Fernandez-Moure JS. Amniotic fluid allograft enhances the host response to ventral hernia repair using acellular dermal matrix. J Tissue Eng Regen Med 2021; 15:1092-1104. [PMID: 34599552 DOI: 10.1002/term.3255] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/22/2021] [Revised: 08/19/2021] [Accepted: 08/31/2021] [Indexed: 11/08/2022]
Abstract
Ventral hernia repair (VHR) with acellular dermal matrix (ADM) has high rates of recurrence that may be improved with allogeneic growth factor augmentation such as amniotic fluid allograft (AFA). We hypothesized that AFA would modulate the host response to improve ADM incorporation in VHR. Lewis rats underwent chronic VHR with porcine ADM alone or with AFA augmentation. Tissue harvested at 3, 14, or 28 days was assessed for region-specific cellularity, and a validated histomorphometric score was generated for tissue incorporation. Expression of pro-inflammatory (Nos1, Tnfα), anti-inflammatory (Arg1, Il-10, Mrc1) and tissue regeneration (Col1a1, Col3a1, Vegf, and alpha actinin-2) genes were quantified using quantitative reverse-transcription polymerase chain reaction. Amniotic fluid allograft treatment caused enhanced vascularization and cellularization translating to increased histomorphometric scores at 14 days, likely mediated by upregulation of pro-regeneration genes throughout the study period and molecular evidence of anti-inflammatory, M2-polarized macrophage phenotype. Collectively, this suggests AFA may have a therapeutic role as a VHR adjunct.
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Affiliation(s)
- Jeffrey L Van Eps
- Department of Surgery, Section of Colon & Rectal Surgery, University of Texas Health Science Center, McGovern Medical School, Houston, Texas, USA
| | - Christian Boada
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, Texas, USA
- Department of Houston Methodist Orthopedic and Sports Medicine, Houston Methodist Hospital, Houston, Texas, USA
| | - Jacob C Scherba
- Department of Biomedical Engineering, Duke University, Durham, North Carolina, USA
| | - Dmitry Zavlin
- Department of Surgery, Plastic & Reconstructive Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | - Noemi Arrighetti
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, Texas, USA
| | - Aaron Shi
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, Texas, USA
| | - Xin Wang
- Center for Musculoskeletal Regeneration, Houston Methodist Research Institute, Houston, Texas, USA
| | - Ennio Tasciotti
- Department of Human Sciences and Quality of Life Promotion, University San Raffaele and IRCCS San Raffaele, Rome, Italy
| | - Joseph F Buell
- Department of Surgery, Mission Health, Asheville, North Carolina, USA
| | - Warren A Ellsworth
- Department of Surgery, Plastic & Reconstructive Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | - Daniel J Bonville
- Department of Surgery, Division of Acute Care Surgery, Houston Methodist Hospital, Houston, Texas, USA
| | - Joseph S Fernandez-Moure
- Department of Surgery, Division of Trauma, Acute, and Critical Care Surgery, Duke University Medical Center, Durham, North Carolina, USA
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10
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Afami ME, El Karim I, About I, Krasnodembskaya AD, Laverty G, Lundy FT. Multicomponent Peptide Hydrogels as an Innovative Platform for Cell-Based Tissue Engineering in the Dental Pulp. Pharmaceutics 2021; 13:1575. [PMID: 34683868 PMCID: PMC8539061 DOI: 10.3390/pharmaceutics13101575] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/14/2021] [Revised: 09/20/2021] [Accepted: 09/22/2021] [Indexed: 11/17/2022] Open
Abstract
In light of the increasing levels of antibiotic resistance, nanomaterials and novel biologics are urgently required to manage bacterial infections. To date, commercially available self-assembling peptide hydrogels have not been studied extensively for their ability to inhibit micro-organisms relevant to tissue engineering sites such as dental root canals. In this work, we assess the biocompatibility of dental pulp stem/stromal cells with commercially available multicomponent peptide hydrogels. We also determine the effects of dental pulp stem/stromal cell (DPSC) culture in hydrogels on growth factor/cytokine expression. Furthermore, to investigate novel aspects of self-assembling peptide hydrogels, we determine their antimicrobial activity against the oral pathogens Staphylococcus aureus, Enterococcus faecalis, and Fusobacterium nucleatum. We show that self-assembling peptide hydrogels and hydrogels functionalized with the adhesion motif Arg-Gly-Asp (RGD) are biocompatible with DPSCs, and that cells grown in 3D hydrogel cultures produce a discrete secretome compared with 2D-cultured cells. Furthermore, we show that soluble peptides and assembled hydrogels have antimicrobial effects against oral pathogens. Given their antibacterial activity against oral pathogens, biocompatibility with dental pulp stem/stromal cells and enhancement of an angiogenic secretome, multicomponent peptide hydrogels hold promise for translational use.
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Affiliation(s)
- Marina E. Afami
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; (M.E.A.); (I.E.K.); (A.D.K.)
| | - Ikhlas El Karim
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; (M.E.A.); (I.E.K.); (A.D.K.)
| | - Imad About
- Aix Marseille Univ, CNRS, ISM, Inst Movement Sci, 13385 Marseille, France;
| | - Anna D. Krasnodembskaya
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; (M.E.A.); (I.E.K.); (A.D.K.)
| | - Garry Laverty
- School of Pharmacy, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK;
| | - Fionnuala T. Lundy
- Wellcome-Wolfson Institute for Experimental Medicine, School of Medicine, Dentistry and Biomedical Sciences, Queen’s University Belfast, 97 Lisburn Road, Belfast BT9 7BL, UK; (M.E.A.); (I.E.K.); (A.D.K.)
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11
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Narasimhan B, Narasimhan H, Lorente-Ros M, Romeo FJ, Bhatia K, Aronow WS. Therapeutic angiogenesis in coronary artery disease: a review of mechanisms and current approaches. Expert Opin Investig Drugs 2021; 30:947-963. [PMID: 34346802 DOI: 10.1080/13543784.2021.1964471] [Citation(s) in RCA: 10] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/31/2021] [Accepted: 08/02/2021] [Indexed: 12/11/2022]
Abstract
INTRODUCTION Despite tremendous advances, the shortcomings of current therapies for coronary disease are evidenced by the fact that it remains the leading cause of death in many parts of the world. There is hence a drive to develop novel therapies to tackle this disease. Therapeutic approaches to coronary angiogenesis have long been an area of interest in lieu of its incredible, albeit unrealized potential. AREAS COVERED This paper offers an overview of mechanisms of native angiogenesis and a description of angiogenic growth factors. It progresses to outline the advances in gene and stem cell therapy and provides a brief description of other investigational approaches to promote angiogenesis. Finally, the hurdles and limitations unique to this particular area of study are discussed. EXPERT OPINION An effective, sustained, and safe therapeutic option for angiogenesis truly could be the paradigm shift for cardiovascular medicine. Unfortunately, clinically meaningful therapeutic options remain elusive because promising animal studies have not been replicated in human trials. The sheer complexity of this process means that numerous major hurdles remain before therapeutic angiogenesis truly makes its way from the bench to the bedside.
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Affiliation(s)
- Bharat Narasimhan
- Department Of Medicine, Mount Sinai St.Lukes-Roosevelt, Icahn School Of Medicine At Mount Sinai, New York, NY, USA
| | | | - Marta Lorente-Ros
- Department Of Medicine, Mount Sinai St.Lukes-Roosevelt, Icahn School Of Medicine At Mount Sinai, New York, NY, USA
| | - Francisco Jose Romeo
- Department Of Medicine, Mount Sinai St.Lukes-Roosevelt, Icahn School Of Medicine At Mount Sinai, New York, NY, USA
| | - Kirtipal Bhatia
- Department Of Medicine, Mount Sinai St.Lukes-Roosevelt, Icahn School Of Medicine At Mount Sinai, New York, NY, USA
| | - Wilbert S Aronow
- Department of Cardiology, Westchester Medical Center/New York Medical College, Valhalla, NY, USA
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12
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Borrelli MA, Turnquist HR, Little SR. Biologics and their delivery systems: Trends in myocardial infarction. Adv Drug Deliv Rev 2021; 173:181-215. [PMID: 33775706 PMCID: PMC8178247 DOI: 10.1016/j.addr.2021.03.014] [Citation(s) in RCA: 28] [Impact Index Per Article: 7.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/29/2020] [Revised: 03/14/2021] [Accepted: 03/20/2021] [Indexed: 02/07/2023]
Abstract
Cardiovascular disease is the leading cause of death around the world, in which myocardial infarction (MI) is a precipitating event. However, current therapies do not adequately address the multiple dysregulated systems following MI. Consequently, recent studies have developed novel biologic delivery systems to more effectively address these maladies. This review utilizes a scientometric summary of the recent literature to identify trends among biologic delivery systems designed to treat MI. Emphasis is placed on sustained or targeted release of biologics (e.g. growth factors, nucleic acids, stem cells, chemokines) from common delivery systems (e.g. microparticles, nanocarriers, injectable hydrogels, implantable patches). We also evaluate biologic delivery system trends in the entire regenerative medicine field to identify emerging approaches that may translate to the treatment of MI. Future developments include immune system targeting through soluble factor or chemokine delivery, and the development of advanced delivery systems that facilitate the synergistic delivery of biologics.
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Affiliation(s)
- Matthew A Borrelli
- Department of Chemical Engineering, University of Pittsburgh, 940 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15213, USA.
| | - Heth R Turnquist
- Starzl Transplantation Institute, 200 Darragh St, Pittsburgh, PA 15213, USA; Department of Surgery, University of Pittsburgh School of Medicine, Pittsburgh, PA 15213, USA; Department of Immunology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA.
| | - Steven R Little
- Department of Chemical Engineering, University of Pittsburgh, 940 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15213, USA; Department of Bioengineering, University of Pittsburgh, 302 Benedum Hall, 3700 O'Hara Street, Pittsburgh, PA 15213, USA; Department of Clinical and Translational Science, University of Pittsburgh, Forbes Tower, Suite 7057, Pittsburgh, PA 15213, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, 450 Technology Drive, Suite 300, Pittsburgh, PA 15219, USA; Department of Immunology, University of Pittsburgh, 200 Lothrop Street, Pittsburgh, PA 15213, USA; Department of Pharmaceutical Science, University of Pittsburgh, 3501 Terrace Street, Pittsburgh, PA 15213, USA; Department of Ophthalmology, University of Pittsburgh, 203 Lothrop Street, Pittsburgh, PA 15213, USA.
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13
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Ultrashort Peptide Hydrogels Display Antimicrobial Activity and Enhance Angiogenic Growth Factor Release by Dental Pulp Stem/Stromal Cells. MATERIALS 2021; 14:ma14092237. [PMID: 33925337 PMCID: PMC8123614 DOI: 10.3390/ma14092237] [Citation(s) in RCA: 12] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 03/30/2021] [Revised: 04/20/2021] [Accepted: 04/22/2021] [Indexed: 12/26/2022]
Abstract
Recent studies on peptide hydrogels have shown that ultrashort peptides (<8 amino acids) can self-assemble into hydrogels. Ultrashort peptides can be designed to incorporate antimicrobial motifs, such as positively charged lysine residues, so that the peptides have inherent antimicrobial characteristics. Antimicrobial hydrogels represent a step change in tissue engineering and merit further investigation, particularly in applications where microbial infection could compromise healing. Herein, we studied the biocompatibility of dental pulp stem/stromal cells (DPSCs) with an ultrashort peptide hydrogel, (naphthalene-2-ly)-acetyl-diphenylalanine-dilysine-OH (NapFFεKεK-OH), where the epsilon (ε) amino group forms part of the peptide bond rather than the standard amino grouping. We tested the antimicrobial properties of NapFFεKεK-OH in both solution and hydrogel form against Staphylococcus aureus, Enterococcus faecalis and Fusobacterium nucleatum and investigated the DPSC secretome in hydrogel culture. Our results showed NapFFεKεK-OH hydrogels were biocompatible with DPSCs. Peptides in solution form were efficacious against biofilms of S. aureus and E. faecalis, whereas hydrogels demonstrated antimicrobial activity against E. faecalis and F. nucleatum. Using an angiogenic array we showed that DPSCs encapsulated within NapFFεKεK-OH hydrogels produced an angiogenic secretome. These results suggest that NapFFεKεK-OH hydrogels have potential to serve as novel hydrogels in tissue engineering for cell-based pulp regeneration.
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14
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Wang H, Liu R, Wang S, Guan Y, Zhang Y. A highly programmable platform for sequential release of protein therapeutics. J Mater Chem B 2021; 9:1616-1624. [PMID: 33475126 DOI: 10.1039/d0tb02657c] [Citation(s) in RCA: 5] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/21/2022]
Abstract
Drug carriers capable of releasing multiple protein therapeutics in an appropriate sequence are highly desirable for the treatment of many diseases. However current systems only allow the sequential release of two or three proteins, and it is difficult to adjust the time intervals between them. Here to solve these problems a new system is designed. The proteins are first encapsulated in CaCO3 microspheres. Then the microspheres are coated with hydrogen-bonded tannic acid (TA)/polyethylene glycol (PEG) layer-by-layer films. The encapsulated protein does not release from the microsphere until the TA/PEG coating is fully disintegrated. As the TA/PEG coating is eroded at a constant rate, the lag time for protein release is proportional to the coating thickness. To achieve sequential release, one can simply coat the protein-encapsulated microspheres with different thickness TA/PEG films and then mix them. Both in vitro and in vivo tests demonstrate that the proteins can be released from the mixed samples in a sequence according to the thickness of the TA/PEG coatings. The time intervals between the protein releases can be facilely adjusted by adjusting the thickness of the TA/PEG coatings. In addition, sequential release of more than 3 proteins can be facilely achieved.
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Affiliation(s)
- Haozheng Wang
- Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Rui Liu
- Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Sha Wang
- Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Ying Guan
- Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China.
| | - Yongjun Zhang
- Key Laboratory of Functional Polymer Materials and State Key Laboratory of Medicinal Chemical Biology, Institute of Polymer Chemistry, College of Chemistry, Nankai University, Tianjin 300071, China. and School of Material Science and Engineering, Tiangong University, Tianjin 300387, China
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15
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Beyond Growth Factors: Macrophage-Centric Strategies for Angiogenesis. CURRENT PATHOBIOLOGY REPORTS 2020. [DOI: 10.1007/s40139-020-00215-9] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
Abstract
AbstractFunctional angiogenesis is a critical therapeutic goal in many pathological conditions. Logically, the use of pro-angiogenic growth factors has been the mainstay approach despite obvious limitations and modest success. Recently, macrophages have been identified as key regulators of the host response to implanted materials. Particularly, our understanding of dynamically plastic macrophage phenotypes, their interactions with biomaterials, and varied roles in different stages of angiogenic processes is evolving rapidly. In this review, we discuss changing perspectives on therapeutic angiogenesis, in relation to implantable materials and macrophage-centric strategies therein. Harnessing the different mechanisms through which the macrophage-driven host response is involved in angiogenesis has great potential for improving clinical outcome.
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16
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Kumar AS, Kamalasanan K. Drug delivery to optimize angiogenesis imbalance in keloid: A review. J Control Release 2020; 329:1066-1076. [PMID: 33091533 DOI: 10.1016/j.jconrel.2020.10.035] [Citation(s) in RCA: 20] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/19/2020] [Revised: 10/16/2020] [Accepted: 10/17/2020] [Indexed: 12/12/2022]
Abstract
The wound healing process involves three continuous stages. Where, any imbalance can lead to the formation of unwanted keloids, hypertrophic scar, or tumors. Keloids are any unpleasant, non-compliant comorbidity affecting a major section of people around the globe who acquire it either genetically or by pathological means as a result of a skin injury. Angiogenesis is unavoidable in the healing process after an injury or disruption of skin to promote tissue regeneration. Uncontrolled angiogenesis during the healing process can initiate the unwanted response in the wound that facilitate keloid. Angiogenic therapy is adapted to accelerate healing after an injury. Else ways, there exists a risk of keloid formation due to excessive angiogenesis during the wound healing process. There are numerous strategies to treat keloid. Anti-angiogenic factors are provided to patients post-surgery to prevent the keloid formation; however, they come into the picture after the formation of keloid. The available strategies to treat keloids are steroidal injections, surgical excision of the keloid, radiotherapy, pressure therapy, the use of cryosurgery, and many more. The available treatments are not promising in reducing the recurrent rate of keloids as there are chances of high re-occurrences with similar/larger lesions on the removed keloid site. In this review, we are discussing the importance of controlled angiogenesis with the help of controlled drug delivery strategies enabling the wound healing process without the induction of keloid.
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Affiliation(s)
- Aishwari S Kumar
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, AIMS Ponekkara PO, Kochi, Kerala, 682041, India
| | - Kaladhar Kamalasanan
- Department of Pharmaceutics, Amrita School of Pharmacy, Amrita Vishwa Vidyapeetham, AIMS Health Sciences Campus, AIMS Ponekkara PO, Kochi, Kerala, 682041, India.
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17
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Aliabouzar M, Jivani A, Lu X, Kripfgans OD, Fowlkes JB, Fabiilli ML. Standing wave-assisted acoustic droplet vaporization for single and dual payload release in acoustically-responsive scaffolds. ULTRASONICS SONOCHEMISTRY 2020; 66:105109. [PMID: 32248042 PMCID: PMC7217719 DOI: 10.1016/j.ultsonch.2020.105109] [Citation(s) in RCA: 18] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 11/10/2019] [Revised: 03/20/2020] [Accepted: 03/25/2020] [Indexed: 05/04/2023]
Abstract
An ultrasound standing wave field (SWF) has been utilized in many biomedical applications. Here, we demonstrate how a SWF can enhance drug release using acoustic droplet vaporization (ADV) in an acoustically-responsive scaffold (ARS). ARSs are composite fibrin hydrogels containing payload-carrying, monodispersed perfluorocarbon (PFC) emulsions and have been used to stimulate regenerative processes such as angiogenesis. Elevated amplitudes in the SWF significantly enhanced payload release from ARSs containing dextran-loaded emulsions (nominal diameter: 6 μm) compared to the -SWF condition, both at sub- and suprathreshold excitation pressures. At 2.5 MHz and 4 MPa peak rarefactional pressure, the cumulative percentage of payload released from ARSs reached 84.1 ± 5.4% and 66.1 ± 4.4% under + SWF and -SWF conditions, respectively, on day 10. A strategy for generating a SWF for an in situ ARS is also presented. For dual-payload release studies, bi-layer ARSs containing a different payload within each layer were exposed to temporally staggered ADV at 3.25 MHz (day 0) and 8.6 MHz (day 4). Sequential payload release was demonstrated using dextran payloads as well as two growth factors relevant to angiogenesis: basic fibroblast growth factor (bFGF) and platelet-derived growth factor BB (PDGF-BB). In addition, bubble growth and fibrin degradation were characterized in the ARSs under +SWF and -SWF conditions. These results highlight the utility of a SWF for modulating single and dual payload release from an ARS and can be used in future therapeutic studies.
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Affiliation(s)
- Mitra Aliabouzar
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA
| | - Aniket Jivani
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Depatment of Mechanical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Xiaofang Lu
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA
| | - Oliver D Kripfgans
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - J Brian Fowlkes
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA
| | - Mario L Fabiilli
- Department of Radiology, University of Michigan, Ann Arbor, MI, USA; Applied Physics Program, University of Michigan, Ann Arbor, MI, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI, USA.
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18
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Mastrullo V, Cathery W, Velliou E, Madeddu P, Campagnolo P. Angiogenesis in Tissue Engineering: As Nature Intended? Front Bioeng Biotechnol 2020; 8:188. [PMID: 32266227 PMCID: PMC7099606 DOI: 10.3389/fbioe.2020.00188] [Citation(s) in RCA: 121] [Impact Index Per Article: 24.2] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/16/2019] [Accepted: 02/26/2020] [Indexed: 12/12/2022] Open
Abstract
Despite the steady increase in the number of studies focusing on the development of tissue engineered constructs, solutions delivered to the clinic are still limited. Specifically, the lack of mature and functional vasculature greatly limits the size and complexity of vascular scaffold models. If tissue engineering aims to replace large portions of tissue with the intention of repairing significant defects, a more thorough understanding of the mechanisms and players regulating the angiogenic process is required in the field. This review will present the current material and technological advancements addressing the imperfect formation of mature blood vessels within tissue engineered structures.
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Affiliation(s)
- Valeria Mastrullo
- Section of Cardiovascular Sciences, Department of Biochemical Sciences, University of Surrey, Guildford, United Kingdom
| | - William Cathery
- Experimental Cardiovascular Medicine, Bristol Heart Institute, Bristol Royal Infirmary, University of Bristol, Bristol, United Kingdom
| | - Eirini Velliou
- Bioprocess and Biochemical Engineering Group (BioProChem), Department of Chemical and Process Engineering, University of Surrey, Guildford, United Kingdom
| | - Paolo Madeddu
- Experimental Cardiovascular Medicine, Bristol Heart Institute, Bristol Royal Infirmary, University of Bristol, Bristol, United Kingdom
| | - Paola Campagnolo
- Section of Cardiovascular Sciences, Department of Biochemical Sciences, University of Surrey, Guildford, United Kingdom
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19
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Wei Z, Volkova E, Blatchley MR, Gerecht S. Hydrogel vehicles for sequential delivery of protein drugs to promote vascular regeneration. Adv Drug Deliv Rev 2019; 149-150:95-106. [PMID: 31421149 PMCID: PMC6889011 DOI: 10.1016/j.addr.2019.08.005] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/25/2019] [Revised: 07/04/2019] [Accepted: 08/12/2019] [Indexed: 12/12/2022]
Abstract
In recent years, as the mechanisms of vasculogenesis and angiogenesis have been uncovered, the functions of various pro-angiogenic growth factors (GFs) and cytokines have been identified. Therefore, therapeutic angiogenesis, by delivery of GFs, has been sought as a treatment for many vascular diseases. However, direct injection of these protein drugs has proven to have limited clinical success due to their short half-lives and systemic off-target effects. To overcome this, hydrogel carriers have been developed to conjugate single or multiple GFs with controllable, sustained, and localized delivery. However, these attempts have failed to account for the temporal complexity of natural angiogenic pathways, resulting in limited therapeutic effects. Recently, the emerging ideas of optimal sequential delivery of multiple GFs have been suggested to better mimic the biological processes and to enhance therapeutic angiogenesis. Incorporating sequential release into drug delivery platforms will likely promote the formation of neovasculature and generate vast therapeutic potential.
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Affiliation(s)
- Zhao Wei
- Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Eugenia Volkova
- Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA
| | - Michael R Blatchley
- Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
| | - Sharon Gerecht
- Department of Chemical and Biomolecular Engineering, The Institute for NanoBioTechnology Physical-Sciences Oncology Center, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Biomedical Engineering, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA; Department of Materials Science and Engineering, Johns Hopkins University, Baltimore, MD 21218, USA; Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
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20
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Ong W, Pinese C, Chew SY. Scaffold-mediated sequential drug/gene delivery to promote nerve regeneration and remyelination following traumatic nerve injuries. Adv Drug Deliv Rev 2019; 149-150:19-48. [PMID: 30910595 DOI: 10.1016/j.addr.2019.03.004] [Citation(s) in RCA: 24] [Impact Index Per Article: 4.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/14/2018] [Revised: 02/27/2019] [Accepted: 03/19/2019] [Indexed: 02/06/2023]
Abstract
Neural tissue regeneration following traumatic injuries is often subpar. As a result, the field of neural tissue engineering has evolved to find therapeutic interventions and has seen promising outcomes. However, robust nerve and myelin regeneration remain elusive. One possible reason may be the fact that tissue regeneration often follows a complex sequence of events in a temporally-controlled manner. Although several other fields of tissue engineering have begun to recognise the importance of delivering two or more biomolecules sequentially for more complete tissue regeneration, such serial delivery of biomolecules in neural tissue engineering remains limited. This review aims to highlight the need for sequential delivery to enhance nerve regeneration and remyelination after traumatic injuries in the central nervous system, using spinal cord injuries as an example. In addition, possible methods to attain temporally-controlled drug/gene delivery are also discussed for effective neural tissue regeneration.
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21
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Ji L, Song Z, Zeng F, Hu M, Chen S, Qin Z, Xia D. [Research progress on controlled release of various growth factors in bone regeneration]. ZHONGGUO XIU FU CHONG JIAN WAI KE ZA ZHI = ZHONGGUO XIUFU CHONGJIAN WAIKE ZAZHI = CHINESE JOURNAL OF REPARATIVE AND RECONSTRUCTIVE SURGERY 2019; 33:750-755. [PMID: 31198005 PMCID: PMC8355764 DOI: 10.7507/1002-1892.201901116] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Subscribe] [Scholar Register] [Received: 01/28/2019] [Revised: 04/28/2019] [Indexed: 11/03/2022]
Abstract
OBJECTIVE To summarize the research progress of controlled release of angiogenic factors and osteogenic factors in bone tissue engineering. METHODS The domestic and abroad literature on the controlled release structure of growth factors during bone regeneration in recent years was extensively reviewed and summarized. RESULTS The sustained-release structure includes direct binding, microsphere-three-dimensional scaffold structure, core-shell structure, layer self-assembly, hydrogel, and gene carrier. A sustained-release system composed of different sustained-release structures combined with different growth factors can promote bone regeneration and angiogenesis. CONCLUSION Due to its controllability and persistence, the growth factor sustained-release system has become a research hotspot in bone tissue engineering and has broad application prospects.
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Affiliation(s)
- Lin Ji
- Department of Burn and Plastic Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China
| | - Ziwei Song
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China
| | - Fuhai Zeng
- Department of Burn and Plastic Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China
| | - Ming Hu
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China
| | - Siqi Chen
- Department of Burn and Plastic Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China
| | - Zhongjie Qin
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000, P.R.China
| | - Delin Xia
- Department of Oral and Maxillofacial Surgery, the Affiliated Hospital of Southwest Medical University, Luzhou Sichuan, 646000,
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22
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Gaspar D, Peixoto R, De Pieri A, Striegl B, Zeugolis DI, Raghunath M. Local pharmacological induction of angiogenesis: Drugs for cells and cells as drugs. Adv Drug Deliv Rev 2019; 146:126-154. [PMID: 31226398 DOI: 10.1016/j.addr.2019.06.002] [Citation(s) in RCA: 13] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/18/2018] [Revised: 05/12/2019] [Accepted: 06/16/2019] [Indexed: 12/12/2022]
Abstract
The past decades have seen significant advances in pro-angiogenic strategies based on delivery of molecules and cells for conditions such as coronary artery disease, critical limb ischemia and stroke. Currently, three major strategies are evolving. Firstly, various pharmacological agents (growth factors, interleukins, small molecules, DNA/RNA) are locally applied at the ischemic region. Secondly, preparations of living cells with considerable bandwidth of tissue origin, differentiation state and preconditioning are delivered locally, rarely systemically. Thirdly, based on the notion, that cellular effects can be attributed mostly to factors secreted in situ, the cellular secretome (conditioned media, exosomes) has come into the spotlight. We review these three strategies to achieve (neo)angiogenesis in ischemic tissue with focus on the angiogenic mechanisms they tackle, such as transcription cascades, specific signalling steps and cellular gases. We also include cancer-therapy relevant lymphangiogenesis, and shall seek to explain why there are often conflicting data between in vitro and in vivo. The lion's share of data encompassing all three approaches comes from experimental animal work and we shall highlight common technical obstacles in the delivery of therapeutic molecules, cells, and secretome. This plethora of preclinical data contrasts with a dearth of clinical studies. A lack of adequate delivery vehicles and standardised assessment of clinical outcomes might play a role here, as well as regulatory, IP, and manufacturing constraints of candidate compounds; in addition, completed clinical trials have yet to reveal a successful and efficacious strategy. As the biology of angiogenesis is understood well enough for clinical purposes, it will be a matter of time to achieve success for well-stratified patients, and most probably with a combination of compounds.
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Affiliation(s)
- Diana Gaspar
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland
| | - Rita Peixoto
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland
| | - Andrea De Pieri
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Proxy Biomedical Ltd., Coilleach, Spiddal, Galway, Ireland
| | - Britta Striegl
- Competence Centre Tissue Engineering for Drug Development (TEDD), Centre for Cell Biology & Tissue Engineering, Institute for Chemistry and Biotechnology, Zurich University of Applied Sciences, Zurich, Switzerland
| | - Dimitrios I Zeugolis
- Regenerative, Modular & Developmental Engineering Laboratory (REMODEL), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland; Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences Building, National University of Ireland Galway (NUI Galway), Galway, Ireland
| | - Michael Raghunath
- Competence Centre Tissue Engineering for Drug Development (TEDD), Centre for Cell Biology & Tissue Engineering, Institute for Chemistry and Biotechnology, Zurich University of Applied Sciences, Zurich, Switzerland.
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23
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The Role of Platelets in the Tumor-Microenvironment and the Drug Resistance of Cancer Cells. Cancers (Basel) 2019; 11:cancers11020240. [PMID: 30791448 PMCID: PMC6406993 DOI: 10.3390/cancers11020240] [Citation(s) in RCA: 86] [Impact Index Per Article: 14.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2019] [Revised: 01/29/2019] [Accepted: 02/15/2019] [Indexed: 02/06/2023] Open
Abstract
Besides the critical functions in hemostasis, thrombosis and the wounding process, platelets have been increasingly identified as active players in various processes in tumorigenesis, including angiogenesis and metastasis. Once activated, platelets can release bioactive contents such as lipids, microRNAs, and growth factors into the bloodstream, subsequently enhancing the platelet⁻cancer interaction and stimulating cancer metastasis and angiogenesis. The mechanisms of treatment failure of chemotherapeutic drugs have been investigated to be associated with platelets. Therefore, understanding how platelets contribute to the tumor microenvironment may potentially identify strategies to suppress cancer angiogenesis, metastasis, and drug resistance. Herein, we present a review of recent investigations on the role of platelets in the tumor-microenvironment including angiogenesis, and metastasis, as well as targeting platelets for cancer treatment, especially in drug resistance.
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Moncion A, Lin M, Kripfgans OD, Franceschi RT, Putnam AJ, Fabiilli ML. Sequential Payload Release from Acoustically-Responsive Scaffolds Using Focused Ultrasound. ULTRASOUND IN MEDICINE & BIOLOGY 2018; 44:2323-2335. [PMID: 30077413 PMCID: PMC6441330 DOI: 10.1016/j.ultrasmedbio.2018.06.011] [Citation(s) in RCA: 25] [Impact Index Per Article: 3.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/23/2018] [Revised: 06/14/2018] [Accepted: 06/19/2018] [Indexed: 05/13/2023]
Abstract
Regenerative processes, such as angiogenesis and osteogenesis, often require multiple growth factors with distinct spatiotemporal patterns and expression sequences. Within tissue engineering, hydrogel scaffolds are commonly used for exogenous growth factor delivery. However, direct incorporation of growth factors within conventional hydrogels does not afford spatiotemporally controlled delivery because release is governed by passive mechanisms that cannot be actively controlled after the scaffold is implanted. We have developed acoustically-responsive scaffolds (ARSs), which are fibrin scaffolds doped with payload-containing, sonosensitive emulsions. Payload release from ARSs can be controlled non-invasively and on demand using focused, megahertz-range ultrasound. In the in vitro study described here, we developed and characterized ARSs that enable sequential release of two surrogate, fluorescent payloads using consecutive ultrasound exposures at different acoustic pressures. ARSs were generated with various combinations and volume fractions of perfluoropentane, perfluorohexane, and perfluoroheptane emulsions. Acoustic droplet vaporization and inertial cavitation thresholds correlated with the boiling point/molecular weight of the perfluorocarbon while payload release correlated inversely. Payload release was longitudinally measured and observed to follow a sigmoidal trend versus acoustic pressure. Perfluoropentane and perfluorohexane emulsions were stabilized when incorporated into ARSs with perfluoroheptane emulsion. These results highlight the potential of using ARSs for sequential, dual-payload release for tissue regeneration.
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Affiliation(s)
- Alexander Moncion
- Applied Physics Program, University of Michigan, Ann Arbor, Michigan, USA; Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA.
| | - Melissa Lin
- Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA
| | - Oliver D Kripfgans
- Applied Physics Program, University of Michigan, Ann Arbor, Michigan, USA; Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
| | - Renny T Franceschi
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA; School of Dentistry, University of Michigan, Ann Arbor, Michigan, USA; Department of Biological Chemistry, University of Michigan Medical School, Ann Arbor, Michigan, USA
| | - Andrew J Putnam
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
| | - Mario L Fabiilli
- Applied Physics Program, University of Michigan, Ann Arbor, Michigan, USA; Department of Radiology, University of Michigan Health System, Ann Arbor, Michigan, USA; Department of Biomedical Engineering, University of Michigan, Ann Arbor, Michigan, USA
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Abstract
This overview article for the Comprehensive Physiology collection is focused on detailing platelets, how platelets respond to various stimuli, how platelets interact with their external biochemical environment, and the role of platelets in physiological and pathological processes. Specifically, we will discuss the four major functions of platelets: activation, adhesion, aggregation, and inflammation. We will extend this discussion to include various mechanisms that can induce these functional changes and a discussion of some of the salient receptors that are responsible for platelets interacting with their external environment. We will finish with a discussion of how platelets interact with their vascular environment, with a special focus on interactions with the extracellular matrix and endothelial cells, and finally how platelets can aid and possibly initiate the progression of various vascular diseases. Throughout this overview, we will highlight both the historical investigations into the role of platelets in health and disease as well as some of the more current work. Overall, the authors aim for the readers to gain an appreciation for the complexity of platelet functions and the multifaceted role of platelets in the vascular system. © 2017 American Physiological Society. Compr Physiol 8:1117-1156, 2018.
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Affiliation(s)
- David A Rubenstein
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA
| | - Wei Yin
- Department of Biomedical Engineering, Stony Brook University, Stony Brook, New York, USA
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Three-dimensional computational model simulating the fracture healing process with both biphasic poroelastic finite element analysis and fuzzy logic control. Sci Rep 2018; 8:6744. [PMID: 29712979 PMCID: PMC5928059 DOI: 10.1038/s41598-018-25229-7] [Citation(s) in RCA: 14] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/13/2017] [Accepted: 04/17/2018] [Indexed: 01/28/2023] Open
Abstract
A dynamic model regulated by both biphasic poroelastic finite element analysis and fuzzy logic control was established. Fuzzy logic control was an easy and comprehensive way to simulate the tissue differentiation process, and it is convenient for researchers and medical experts to communicate with one another to change the fuzzy logic rules and improve the simulation of the tissue differentiation process. In this study, a three-dimensional fracture healing model with two different interfragmentary movements (case A: 0.25 mm and case B: 1.25 mm) was analysed with the new set-up computational model. As the healing process proceeded, both simulated interfragmentary movements predicted a decrease and the time that the decrease started for case B was later than that for case A. Compared with experimental results, both cases corresponded with experimental data well. The newly established dynamic model can simulate the healing process under different mechanical environments and has the potential to extend to the multiscale healing model, which is essential for reducing the animal experiments and helping to characterise the complex dynamic interaction between tissue differentiations within the callus region.
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Wang M, Yang N. A review of bioregulatory and coupled mechanobioregulatory mathematical models for secondary fracture healing. Med Eng Phys 2017; 48:90-102. [DOI: 10.1016/j.medengphy.2017.06.031] [Citation(s) in RCA: 7] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/14/2017] [Revised: 05/18/2017] [Accepted: 06/18/2017] [Indexed: 01/09/2023]
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Sphingosine 1-phosphate (S1P) signalling: Role in bone biology and potential therapeutic target for bone repair. Pharmacol Res 2017; 125:232-245. [PMID: 28855094 DOI: 10.1016/j.phrs.2017.08.013] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/28/2017] [Revised: 08/22/2017] [Accepted: 08/23/2017] [Indexed: 12/30/2022]
Abstract
The lipid mediator sphingosine 1-phosphate (S1P) affects cellular functions in most systems. Interest in its therapeutic potential has increased following the discovery of its G protein-coupled receptors and the recent availability of agents that can be safely administered in humans. Although the role of S1P in bone biology has been the focus of much less research than its role in the nervous, cardiovascular and immune systems, it is becoming clear that this lipid influences many of the functions, pathways and cell types that play a key role in bone maintenance and repair. Indeed, S1P is implicated in many osteogenesis-related processes including stem cell recruitment and subsequent differentiation, differentiation and survival of osteoblasts, and coupling of the latter cell type with osteoclasts. In addition, S1P's role in promoting angiogenesis is well-established. The pleiotropic effects of S1P on bone and blood vessels have significant potential therapeutic implications, as current therapeutic approaches for critical bone defects show significant limitations. Because of the complex effects of S1P on bone, the pharmacology of S1P-like agents and their physico-chemical properties, it is likely that therapeutic delivery of S1P agents will offer significant advantages compared to larger molecular weight factors. Hence, it is important to explore novel methods of utilizing S1P agents therapeutically, and improve our understanding of how S1P and its receptors modulate bone physiology and repair.
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Bayer EA, Jordan J, Roy A, Gottardi R, Fedorchak MV, Kumta PN, Little SR. * Programmed Platelet-Derived Growth Factor-BB and Bone Morphogenetic Protein-2 Delivery from a Hybrid Calcium Phosphate/Alginate Scaffold. Tissue Eng Part A 2017; 23:1382-1393. [PMID: 28537482 DOI: 10.1089/ten.tea.2017.0027] [Citation(s) in RCA: 22] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/05/2023] Open
Abstract
Bone tissue engineering requires the upregulation of several regenerative stages, including a critical early phase of angiogenesis. Previous studies have suggested that a sequential delivery of platelet-derived growth factor (PDGF) to bone morphogenetic protein-2 (BMP-2) could promote angiogenic tubule formation when delivered to in vitro cocultures of human umbilical vein endothelial cells (HUVECs) and human mesenchymal stem cells (hMSCs). However, it was previously unclear that this PDGF to BMP-2 delivery schedule will result in cell migration into the scaffolding system and affect the later expression of bone markers. Additionally, a controlled delivery system had not yet been engineered for programmed sequential presentation of this particular growth factor. By combining alginate matrices with calcium phosphate scaffolding, a programmed growth factor delivery schedule was achieved. Specifically, a combination of alginate microspheres, alginate hydrogels, and a novel blend of resorbable calcium phosphate-based cement (ReCaPP) was used. PDGF and BMP-2 were sequentially released from this hybrid calcium phosphate/alginate scaffold with the desired 3-day overlap in PDGF to BMP-2 delivery. Using a three-dimensional coculture model, we observed that this sequence of PDGF to BMP-2 delivery influenced both cellular infiltration and alkaline phosphatase (ALP) expression. It was found that the presence of early PDGF delivery increased the distance of cell infiltration into the calcium phosphate/alginate scaffolding in comparison to early BMP-2 delivery and simultaneous PDGF+BMP-2 delivery. It was also observed that hMSCs expressed a greater amount of ALP+ staining in response to scaffolds delivering the sequential PDGF to BMP-2 schedule, when compared with scaffolds delivering no growth factor, or PDGF alone. Importantly, hMSCs cultured with scaffolds releasing the PDGF to BMP-2 schedule showed similar amounts of ALP staining to hMSCs cultured with BMP-2 alone, suggesting that the sequential schedule of PDGF to BMP-2 presentation promotes differentiation of hMSCs toward an osteoblast phenotype while also increasing cellular infiltration of the scaffold.
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Affiliation(s)
- Emily A Bayer
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Jahnelle Jordan
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Abhijit Roy
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Riccardo Gottardi
- 3 Department of Chemical Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,4 Department of Orthopedic Surgery, University of Pittsburgh , Pittsburgh, Pennsylvania.,5 Ri.MED Foundation , Palermo, Italy
| | - Morgan V Fedorchak
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Department of Chemical Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,6 Department of Ophthalmology, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Prashant N Kumta
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Department of Chemical Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,7 Department of Mechanical Engineering and Materials Science, University of Pittsburgh , Pittsburgh, Pennsylvania.,8 Department of Oral Biology, Center for Craniofacial Regeneration, University of Pittsburgh , Pittsburgh, Pennsylvania
| | - Steven R Little
- 1 Department of Bioengineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,2 The McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania.,3 Department of Chemical Engineering, University of Pittsburgh , Pittsburgh, Pennsylvania.,9 Department of Immunology, University of Pittsburgh , Pittsburgh, Pennsylvania
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Chen R, Cai X, Ma K, Zhou Y, Wang Y, Jiang T. The fabrication of double-layered chitosan/gelatin/genipin nanosphere coating for sequential and controlled release of therapeutic proteins. Biofabrication 2017; 9:025028. [DOI: 10.1088/1758-5090/aa70c3] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/26/2022]
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31
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Hernandez MJ, Christman KL. Designing Acellular Injectable Biomaterial Therapeutics for Treating Myocardial Infarction and Peripheral Artery Disease. JACC Basic Transl Sci 2017; 2:212-226. [PMID: 29057375 PMCID: PMC5646282 DOI: 10.1016/j.jacbts.2016.11.008] [Citation(s) in RCA: 42] [Impact Index Per Article: 5.3] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/02/2016] [Revised: 11/22/2016] [Accepted: 11/23/2016] [Indexed: 02/07/2023]
Abstract
As the number of global deaths attributed to cardiovascular disease continues to rise, viable treatments for cardiovascular events such as myocardial infarction (MI) or conditions like peripheral artery disease (PAD) are critical. Recent studies investigating injectable biomaterials have shown promise in promoting tissue regeneration and functional improvement, and in some cases, incorporating other therapeutics further augments the beneficial effects of these biomaterials. In this review, we aim to emphasize the advantages of acellular injectable biomaterial-based therapies, specifically material-alone approaches or delivery of acellular biologics, in regards to manufacturability and the capacity of these biomaterials to regenerate or repair diseased tissue. We will focus on design parameters and mechanisms that maximize therapeutic efficacy, particularly, improved functional perfusion and neovascularization regarding PAD and improved cardiac function and reduced negative left ventricular (LV) remodeling post-MI. We will then discuss the rationale and challenges of designing new injectable biomaterial-based therapies for the clinic.
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Affiliation(s)
| | - Karen L. Christman
- Department of Bioengineering, Sanford Consortium for Regenerative Medicine, University of California San Diego, La Jolla, California
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32
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Kesireddy V, Kasper FK. Approaches for building bioactive elements into synthetic scaffolds for bone tissue engineering. J Mater Chem B 2016; 4:6773-6786. [PMID: 28133536 PMCID: PMC5267491 DOI: 10.1039/c6tb00783j] [Citation(s) in RCA: 45] [Impact Index Per Article: 5.0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/08/2023]
Abstract
Bone tissue engineering (BTE) is emerging as a possible solution for regeneration of bone in a number of applications. For effective utilization, BTE scaffolds often need modifications to impart biological cues that drive diverse cellular functions such as adhesion, migration, survival, proliferation, differentiation, and biomineralization. This review provides an outline of various approaches for building bioactive elements into synthetic scaffolds for BTE and classifies them broadly under two distinct schemes; namely, the top-down approach and the bottom-up approach. Synthetic and natural routes for top-down approaches to production of bioactive constructs for BTE, such as generation of scaffold-extracellular matrix (ECM) hybrid constructs or decellularized and demineralized scaffolds, are provided. Similarly, traditional scaffold-based bottom-up approaches, including growth factor immobilization or peptide-tethered scaffolds, are provided. Finally, a brief overview of emerging bottom-up approaches for generating biologically active constructs for BTE is given. A discussion of the key areas for further investigation, challenges, and opportunities is also presented.
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Affiliation(s)
- Venu Kesireddy
- Department of Orthodontics, The University of Texas Health Science Center at Houston, School of Dentistry
| | - F. Kurtis Kasper
- Department of Orthodontics, The University of Texas Health Science Center at Houston, School of Dentistry
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33
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Bayer EA, Fedorchak MV, Little SR. The Influence of Platelet-Derived Growth Factor and Bone Morphogenetic Protein Presentation on Tubule Organization by Human Umbilical Vascular Endothelial Cells and Human Mesenchymal Stem Cells in Coculture. Tissue Eng Part A 2016; 22:1296-1304. [PMID: 27650131 PMCID: PMC5107722 DOI: 10.1089/ten.tea.2016.0163] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/25/2016] [Accepted: 09/13/2016] [Indexed: 12/12/2022] Open
Abstract
A three-dimensional in vitro Matrigel plug was used as a model to explore delivery patterns of platelet-derived growth factor (PDGF) and bone morphogenetic protein-2 (BMP-2) to a coculture of human mesenchymal and endothelial cells. While BMP-2 is well recognized for its role in promoting fracture healing through proliferation and differentiation of osteoclast precursors, it is not a growth factor known to promote the process of angiogenesis, which is also critical for complete bone tissue repair. PDGF, in contrast, is a known regulator of angiogenesis, and also a powerful chemoattractant for osteoblast precursor cells. It has been suggested that presentation of PDGF followed by BMP may better promote vascularized bone tissue formation. Yet, it is unclear as to how cells would respond to various durations of delivery of each growth factor as well as to various amounts of overlap in presentation in terms of angiogenesis. Using a three-dimensional in vitro Matrigel plug model, we observed how various presentation schedules of PDGF and BMP-2 influenced tubule formation by human mesenchymal stem cells and human umbilical vascular endothelial cells. We observed that sequential presentation of PDGF to BMP-2 led to increased tubule formation over simultaneous delivery of these growth factors. Importantly, a 2-4 day overlap in the sequential presentation of PDGF and BMP-2 increased tubule formation as compared with groups with zero or complete growth factor overlap, suggesting that a moderate amount of angiogenic and osteogenic growth factor overlap may be beneficial for processes associated with angiogenesis.
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Affiliation(s)
- Emily A. Bayer
- Department of Bioengineering, The University of Pittsburgh, Pittsburgh, Pennsylvania
- The McGowan Institute for Regenerative Medicine, The University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Morgan V. Fedorchak
- Department of Bioengineering, The University of Pittsburgh, Pittsburgh, Pennsylvania
- The McGowan Institute for Regenerative Medicine, The University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Chemical Engineering, The University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Ophthalmology, The University of Pittsburgh, Pittsburgh, Pennsylvania
| | - Steven R. Little
- Department of Bioengineering, The University of Pittsburgh, Pittsburgh, Pennsylvania
- The McGowan Institute for Regenerative Medicine, The University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Chemical Engineering, The University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Immunology, The University of Pittsburgh, Pittsburgh, Pennsylvania
- Department of Pharmaceutical Sciences, The University of Pittsburgh, Pittsburgh, Pennsylvania
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Awada HK, Hwang MP, Wang Y. Towards comprehensive cardiac repair and regeneration after myocardial infarction: Aspects to consider and proteins to deliver. Biomaterials 2016; 82:94-112. [PMID: 26757257 PMCID: PMC4872516 DOI: 10.1016/j.biomaterials.2015.12.025] [Citation(s) in RCA: 60] [Impact Index Per Article: 6.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/15/2015] [Revised: 12/15/2015] [Accepted: 12/19/2015] [Indexed: 12/13/2022]
Abstract
Ischemic heart disease is a leading cause of death worldwide. After the onset of myocardial infarction, many pathological changes take place and progress the disease towards heart failure. Pathologies such as ischemia, inflammation, cardiomyocyte death, ventricular remodeling and dilation, and interstitial fibrosis, develop and involve the signaling of many proteins. Proteins can play important roles in limiting or countering pathological changes after infarction. However, they typically have short half-lives in vivo in their free form and can benefit from the advantages offered by controlled release systems to overcome their challenges. The controlled delivery of an optimal combination of proteins per their physiologic spatiotemporal cues to the infarcted myocardium holds great potential to repair and regenerate the heart. The effectiveness of therapeutic interventions depends on the elucidation of the molecular mechanisms of the cargo proteins and the spatiotemporal control of their release. It is likely that multiple proteins will provide a more comprehensive and functional recovery of the heart in a controlled release strategy.
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Affiliation(s)
- Hassan K Awada
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Mintai P Hwang
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Yadong Wang
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA; Vascular Medicine Institute, University of Pittsburgh, Pittsburgh, PA 15261, USA; Clinical and Translational Science Institute, University of Pittsburgh, Pittsburgh, PA 15260, USA.
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Farokhi M, Mottaghitalab F, Shokrgozar MA, Ou KL, Mao C, Hosseinkhani H. Importance of dual delivery systems for bone tissue engineering. J Control Release 2016; 225:152-69. [PMID: 26805518 DOI: 10.1016/j.jconrel.2016.01.033] [Citation(s) in RCA: 117] [Impact Index Per Article: 13.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/11/2015] [Revised: 01/18/2016] [Accepted: 01/19/2016] [Indexed: 02/07/2023]
Abstract
Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering.
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Affiliation(s)
- Mehdi Farokhi
- National Cell Bank of Iran, Pasteur Institute of Iran, Tehran, Iran.
| | - Fatemeh Mottaghitalab
- Nanotechnology Research Center, Faculty of Pharmacy, Tehran University of Medical Sciences, Tehran, Iran
| | | | - Keng-Liang Ou
- Graduate Institute of Biomedical Materials and Tissue Engineering, Taipei Medical University, Taipei, Taiwan; Department of Dentistry, Taipei Medical University - Shuang Ho Hospital, New Taipei city, Taiwan
| | - Chuanbin Mao
- Department of Chemistry and Biochemistry, Stephenson Life Sciences Research Center, University of Oklahoma, Norman, OK 73019, USA
| | - Hossein Hosseinkhani
- Graduate Institute of Biomedical Engineering, National Taiwan University of Science and Technology, Taipei 10607, Taiwan
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Wang YP, Wei ZY, Zhong XF, Lin CJ, Cai YH, Ma J, Zhang YY, Liu YZ, Xing SC. Stable Expression of Basic Fibroblast Growth Factor in Chloroplasts of Tobacco. Int J Mol Sci 2015; 17:E19. [PMID: 26703590 PMCID: PMC4730266 DOI: 10.3390/ijms17010019] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2015] [Revised: 11/30/2015] [Accepted: 12/15/2015] [Indexed: 12/15/2022] Open
Abstract
Basic fibroblast growth factor (bFGF) is a multifunctional factor in acceleration of cell proliferation, differentiation and transference, and therefore widely used in clinical applications. In this study, expression vector pWX-Nt03 harboring a codon-optimized bFGF gene was constructed and introduced into the tobacco chloroplasts by particle bombardment. After four rounds of selection, bFGF was proved to integrate into the chloroplast genome of regenerated plants and two of four transgenic plants were confirmed to be homoplastomic by PCR and Southern hybridization. ELISA assay indicated that bFGF represented approximately 0.1% of total soluble protein in the leaves of transplastomic tobacco plants. This is the first report of bFGF expression via chloroplast transformation in model plant, providing an additional option for the production of chloroplast-produced therapeutic proteins.
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Affiliation(s)
- Yun-Peng Wang
- Jilin Provincial Key Laboratory of Agricultural Biotechnology, Agro-Biotechnology Research Institute, Jilin Academy of Agricultural Sciences, No. 1363, Shengtai st., Changchun 130033, China.
| | - Zheng-Yi Wei
- Jilin Provincial Key Laboratory of Agricultural Biotechnology, Agro-Biotechnology Research Institute, Jilin Academy of Agricultural Sciences, No. 1363, Shengtai st., Changchun 130033, China.
| | - Xiao-Fang Zhong
- Jilin Provincial Key Laboratory of Agricultural Biotechnology, Agro-Biotechnology Research Institute, Jilin Academy of Agricultural Sciences, No. 1363, Shengtai st., Changchun 130033, China.
| | - Chun-Jing Lin
- Jilin Provincial Key Laboratory of Agricultural Biotechnology, Agro-Biotechnology Research Institute, Jilin Academy of Agricultural Sciences, No. 1363, Shengtai st., Changchun 130033, China.
| | - Yu-Hong Cai
- Institute of Agricultural Quality Standard and Testing Technology, Jilin Academy of Agricultural Sciences, No. 1363, Shengtai st., Changchun 130033, China.
| | - Jian Ma
- Faculty of Agronomy, Jilin Agricultural University, No. 2888, Xincheng st., Changchun 130118, China.
| | - Yu-Ying Zhang
- Jilin Provincial Key Laboratory of Agricultural Biotechnology, Agro-Biotechnology Research Institute, Jilin Academy of Agricultural Sciences, No. 1363, Shengtai st., Changchun 130033, China.
- College of Biological Sciences, China Agricultural University, No. 2 West Yuanmingyuan Road, Beijing 100094, China.
| | - Yan-Zhi Liu
- Jilin Provincial Key Laboratory of Agricultural Biotechnology, Agro-Biotechnology Research Institute, Jilin Academy of Agricultural Sciences, No. 1363, Shengtai st., Changchun 130033, China.
| | - Shao-Chen Xing
- Jilin Provincial Key Laboratory of Agricultural Biotechnology, Agro-Biotechnology Research Institute, Jilin Academy of Agricultural Sciences, No. 1363, Shengtai st., Changchun 130033, China.
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Spartalis E, Tomos P, Moris D, Athanasiou A, Markakis C, Spartalis MD, Troupis T, Dimitroulis D, Perrea D. Role of platelet-rich plasma in ischemic heart disease: An update on the latest evidence. World J Cardiol 2015; 7:665-670. [PMID: 26516421 PMCID: PMC4620078 DOI: 10.4330/wjc.v7.i10.665] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/25/2015] [Revised: 07/07/2015] [Accepted: 09/08/2015] [Indexed: 02/06/2023] Open
Abstract
Myocardial infarction is the most common cause of congestive heart failure. Novel strategies such as directly reprogramming cardiac fibroblasts into cardiomyocytes are an exciting area of investigation for repair of injured myocardial tissue. The ultimate goal is to rebuild functional myocardium by transplanting exogenous stem cells or by activating native stem cells to induce endogenous repair. Cell-based myocardial restoration, however, has not penetrated broad clinical practice yet. Platelet-rich plasma, an autologous fractionation of whole blood containing high concentrations of growth factors, has been shown to safely and effectively enhance healing and angiogenesis primarily by reparative cell signaling. In this review, we collected all recent advances in novel therapies as well as experimental evidence demonstrating the role of platelet-rich plasma in ischemic heart disease, focusing on aspects that might be important for future successful clinical application.
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Rambhia KJ, Ma PX. Controlled drug release for tissue engineering. J Control Release 2015; 219:119-128. [PMID: 26325405 DOI: 10.1016/j.jconrel.2015.08.049] [Citation(s) in RCA: 169] [Impact Index Per Article: 16.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2015] [Revised: 08/23/2015] [Accepted: 08/25/2015] [Indexed: 11/19/2022]
Abstract
Tissue engineering is often referred to as a three-pronged discipline, with each prong corresponding to 1) a 3D material matrix (scaffold), 2) drugs that act on molecular signaling, and 3) regenerative living cells. Herein we focus on reviewing advances in controlled release of drugs from tissue engineering platforms. This review addresses advances in hydrogels and porous scaffolds that are synthesized from natural materials and synthetic polymers for the purposes of controlled release in tissue engineering. We pay special attention to efforts to reduce the burst release effect and to provide sustained and long-term release. Finally, novel approaches to controlled release are described, including devices that allow for pulsatile and sequential delivery. In addition to recent advances, limitations of current approaches and areas of further research are discussed.
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Affiliation(s)
- Kunal J Rambhia
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA
| | - Peter X Ma
- Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USA; Department of Biologic and Materials Sciences, University of Michigan, Ann Arbor, MI 48109, USA; Macromolecular Science and Engineering Center, University of Michigan, Ann Arbor, MI 48109, USA; Department of Materials Science and Engineering, University of Michigan, Ann Arbor, MI 48109, USA.
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Bayer EA, Gottardi R, Fedorchak MV, Little SR. The scope and sequence of growth factor delivery for vascularized bone tissue regeneration. J Control Release 2015; 219:129-140. [PMID: 26264834 DOI: 10.1016/j.jconrel.2015.08.004] [Citation(s) in RCA: 56] [Impact Index Per Article: 5.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/31/2015] [Revised: 08/01/2015] [Accepted: 08/03/2015] [Indexed: 12/21/2022]
Abstract
Bone regeneration is a complex process, that in vivo, requires the highly coordinated presentation of biochemical cues to promote the various stages of angiogenesis and osteogenesis. Taking inspiration from the natural healing process, a wide variety of growth factors are currently being released within next generation tissue engineered scaffolds (in a variety of ways) in order to heal non-union fractures and bone defects. This review will focus on the delivery of multiple growth factors to the bone regeneration niche, specifically 1) dual growth factor delivery signaling and crosstalk, 2) the importance of growth factor timing and temporal separation, and 3) the engineering of delivery systems that allow for temporal control over presentation of soluble growth factors. Alternative methods for growth factor presentation, including the use of gene therapy and platelet-rich plasma scaffolds, are also discussed.
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Affiliation(s)
- E A Bayer
- The University of Pittsburgh, Department of Bioengineering, USA; The University of Pittsburgh, The McGowan Institute for Regenerative Medicine, USA
| | - R Gottardi
- The University of Pittsburgh, Department of Chemical Engineering, USA; The University of Pittsburgh, Department of Orthopedic Surgery, USA; The University of Pittsburgh, The McGowan Institute for Regenerative Medicine, USA; RiMED Foundation, Palermo, Italy
| | - M V Fedorchak
- The University of Pittsburgh, Department of Bioengineering, USA; The University of Pittsburgh, Department of Chemical Engineering, USA; The University of Pittsburgh, Department of Ophthalmology, USA; The University of Pittsburgh, The McGowan Institute for Regenerative Medicine, USA
| | - S R Little
- The University of Pittsburgh, Department of Bioengineering, USA; The University of Pittsburgh, Department of Chemical Engineering, USA; The University of Pittsburgh, Department of Immunology, USA; The University of Pittsburgh, The McGowan Institute for Regenerative Medicine, USA.
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Sarker M, Chen X, Schreyer D. Experimental approaches to vascularisation within tissue engineering constructs. JOURNAL OF BIOMATERIALS SCIENCE-POLYMER EDITION 2015; 26:683-734. [DOI: 10.1080/09205063.2015.1059018] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 01/10/2023]
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Awada HK, Johnson NR, Wang Y. Sequential delivery of angiogenic growth factors improves revascularization and heart function after myocardial infarction. J Control Release 2015; 207:7-17. [PMID: 25836592 PMCID: PMC4430430 DOI: 10.1016/j.jconrel.2015.03.034] [Citation(s) in RCA: 98] [Impact Index Per Article: 9.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/24/2014] [Revised: 02/17/2015] [Accepted: 03/30/2015] [Indexed: 12/28/2022]
Abstract
Treatment of ischemia through therapeutic angiogenesis faces significant challenges. Growth factor (GF)-based therapies can be more effective when concerns such as GF spatiotemporal presentation, bioactivity, bioavailability, and localization are addressed. During angiogenesis, vascular endothelial GF (VEGF) is required early to initiate neovessel formation while platelet-derived GF (PDGF-BB) is needed later to stabilize the neovessels. The spatiotemporal delivery of multiple bioactive GFs involved in angiogenesis, in a close mimic to physiological cues, holds great potential to treat ischemic diseases. To achieve sequential release of VEGF and PDGF, we embed VEGF in fibrin gel and PDGF in a heparin-based coacervate that is distributed in the same fibrin gel. In vitro, we show the benefits of this controlled delivery approach on cell proliferation, chemotaxis, and capillary formation. A rat myocardial infarction (MI) model demonstrated the effectiveness of this delivery system in improving cardiac function, ventricular wall thickness, angiogenesis, cardiac muscle survival, and reducing fibrosis and inflammation in the infarct zone compared to saline, empty vehicle, and free GFs. Collectively, our results show that this delivery approach mitigated the injury caused by MI and may serve as a new therapy to treat ischemic hearts pending further examination.
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Affiliation(s)
- Hassan K Awada
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Noah R Johnson
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA
| | - Yadong Wang
- Department of Bioengineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Surgery, University of Pittsburgh, Pittsburgh, PA 15261, USA; Department of Mechanical Engineering and Materials Science, University of Pittsburgh, Pittsburgh, PA 15261, USA; McGowan Institute for Regenerative Medicine, University of Pittsburgh, Pittsburgh, PA 15219, USA.
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Lee JH, Lee YJ, Cho HJ, Kim DW, Shin H. The incorporation of bFGF mediated by heparin into PCL/gelatin composite fiber meshes for guided bone regeneration. Drug Deliv Transl Res 2015; 5:146-59. [PMID: 25787740 DOI: 10.1007/s13346-013-0154-y] [Citation(s) in RCA: 23] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/25/2022]
Abstract
The concept of guided bone regeneration facilitated by barrier membranes has been widely considered to achieve enhanced bone healing in maxillofacial surgery. However, the currently available membranes are limited in their active regulation of cellular activities. In this study, we fabricated polycaprolactone/gelatin composite electrospun nanofibers incorporated with basic fibroblast growth factor (bFGF) to direct bone regeneration. The fibrous morphology was maintained after the crosslinking and subsequent conjugation of heparin. Release of bFGF from electrospun nanofibers without heparin resulted in a spontaneous burst, while the heparin-mediated release of bFGF decreased the burst release in 24 h. The bFGF released from the nanofibers enhanced the proliferation and migration of human mesenchymal stem cells as well as the tubule formation of human umbilical cord blood cells. The subcutaneous implantation of fibers incorporated with bFGF mobilized a large number of cells positive for CD31 and smooth muscle alpha actin within 2 weeks. The effect of the nanofibers incorporated with bFGF on bone regeneration was evaluated on a calvarial critical size defect model. As compared to the mice that received fibers without bFGF, which presented minimal new bone formation (5.36 ± 3.4 % of the defect), those that received implants of heparinized nanofibers incorporated with 50 or 100 ng/mL bFGF significantly enhanced new bone formation (10.82 ± 2.2 and 17.55 ± 6.08 %). Taken together, our results suggest that the electrospun nanofibers incorporating bFGF have the potential to be used as an advanced membrane that actively enhances bone regeneration.
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Affiliation(s)
- Ji-hye Lee
- Department of Bioengineering, Hanyang University, 17 Haengdang-dong, Seongdong-gu, Seoul, 133-791, South Korea
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Li F, Guo W, Li K, Yu M, Tang W, Wang H, Tian W. Improved fat graft survival by different volume fractions of platelet-rich plasma and adipose-derived stem cells. Aesthet Surg J 2015; 35:319-33. [PMID: 25805284 DOI: 10.1093/asj/sju046] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.9] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/19/2022] Open
Abstract
BACKGROUND The success of soft-tissue augmentation is offset by the low survival rates of grafted fat tissue. Research shows that adipose-derived stem cells (ASCs) and platelet-rich plasma (PRP) are beneficial to tissue healing. OBJECTIVES To evaluate the long-term effects of different volume fractions of PRP combined with ASCs on fat graft. METHODS ASCs were isolated from human fat tissue, and PRP was obtained from human blood. Cell count kit-8 and real-time polymerase chain reaction (PCR) were used to evaluate the influence of PRP (0%, 10%, 20%, and 30%; volume/volume [v/v]) in medium on ASC proliferation and adipogenic differentiation, respectively. A novel lipoinjection consisting of granular fat, PRP, and ASCs was subcutaneously transplanted into nude mice. The grafts were volumetrically and histologically evaluated 10, 30, 60, and 90 days after transplantation. RESULTS The addition of PRP improved ASC proliferation. Expression of adipogenic-related genes, peroxisome proliferator-activated receptor-γ, lipoprotein lipase, and adipophilin were up-regulated in PRP-induced ASCs. Compared with other groups, granular fat grafts formed with 20% (v/v) and 30% (v/v) PRP significantly improved residual volumes. More intact adipocytes and capillary formation, but less vacuolization, were observed in the 20% (v/v) and 30% (v/v) PRP groups at 30, 60, and 90 days. However, no significant difference was observed between the 20% (v/v) and 30% (v/v) PRP groups in retaining fat grafts and improving histology. CONCLUSIONS Fat grafting with 20% (v/v) PRP and ASCs constitutes an appropriate transplantation strategy for improving graft survival and provides a potential approach for soft-tissue restoration in plastic and reconstructive surgery.
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Affiliation(s)
- Feng Li
- Dr F. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, P.R. China. Dr Guo is Associate Director at the State Key Laboratory of Oral Diseases and the National EngineeringLaboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Associate Professor in the Department of Pedodontics,West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr K. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Central Sounth University, Changsha, P.R. China. Dr Yu is an Assistant Professor at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China. Drs Tang and Wang are Clinical Professors in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr Tian is Director at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Clinical Professor in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Weihua Guo
- Dr F. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, P.R. China. Dr Guo is Associate Director at the State Key Laboratory of Oral Diseases and the National EngineeringLaboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Associate Professor in the Department of Pedodontics,West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr K. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Central Sounth University, Changsha, P.R. China. Dr Yu is an Assistant Professor at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China. Drs Tang and Wang are Clinical Professors in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr Tian is Director at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Clinical Professor in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Kun Li
- Dr F. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, P.R. China. Dr Guo is Associate Director at the State Key Laboratory of Oral Diseases and the National EngineeringLaboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Associate Professor in the Department of Pedodontics,West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr K. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Central Sounth University, Changsha, P.R. China. Dr Yu is an Assistant Professor at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China. Drs Tang and Wang are Clinical Professors in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr Tian is Director at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Clinical Professor in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Mei Yu
- Dr F. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, P.R. China. Dr Guo is Associate Director at the State Key Laboratory of Oral Diseases and the National EngineeringLaboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Associate Professor in the Department of Pedodontics,West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr K. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Central Sounth University, Changsha, P.R. China. Dr Yu is an Assistant Professor at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China. Drs Tang and Wang are Clinical Professors in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr Tian is Director at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Clinical Professor in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Wei Tang
- Dr F. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, P.R. China. Dr Guo is Associate Director at the State Key Laboratory of Oral Diseases and the National EngineeringLaboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Associate Professor in the Department of Pedodontics,West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr K. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Central Sounth University, Changsha, P.R. China. Dr Yu is an Assistant Professor at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China. Drs Tang and Wang are Clinical Professors in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr Tian is Director at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Clinical Professor in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Hang Wang
- Dr F. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, P.R. China. Dr Guo is Associate Director at the State Key Laboratory of Oral Diseases and the National EngineeringLaboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Associate Professor in the Department of Pedodontics,West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr K. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Central Sounth University, Changsha, P.R. China. Dr Yu is an Assistant Professor at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China. Drs Tang and Wang are Clinical Professors in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr Tian is Director at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Clinical Professor in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
| | - Weidong Tian
- Dr F. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Wenzhou Medical University, Wenzhou, P.R. China. Dr Guo is Associate Director at the State Key Laboratory of Oral Diseases and the National EngineeringLaboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Associate Professor in the Department of Pedodontics,West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr K. Li is a Researcher at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Surgeon in the Department of Oral and Maxillofacial Surgery, School and Hospital of Stomatology, Central Sounth University, Changsha, P.R. China. Dr Yu is an Assistant Professor at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China. Drs Tang and Wang are Clinical Professors in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China. Dr Tian is Director at the State Key Laboratory of Oral Diseases and the National Engineering Laboratory for Oral Regenerative Medicine, Sichuan University, Chengdu, P.R. China; and is a Clinical Professor in the Department of Oral and Maxillofacial Surgery, West China School of Stomatology, Sichuan University, Chengdu, P.R. China
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Glowacki AJ, Gottardi R, Yoshizawa S, Cavalla F, Garlet GP, Sfeir C, Little SR. Strategies to direct the enrichment, expansion, and recruitment of regulatory cells for the treatment of disease. Ann Biomed Eng 2014; 43:593-602. [PMID: 25245220 DOI: 10.1007/s10439-014-1125-2] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/08/2014] [Accepted: 09/12/2014] [Indexed: 01/21/2023]
Abstract
Disease and injury perturb the balance of processes associated with inflammation and tissue remodeling, resulting in positive feedback loops, exacerbation of disease and compromised tissue repair. Conversely, under homeostatic healthy conditions, these processes are tightly regulated through the expansion and/or recruitment of specific cell populations, promoting a balanced steady-state. Better understanding of these regulatory processes and recent advances in biomaterials and biotechnology have prompted strategies to utilize cells for the treatment and prevention of disease through regulation of inflammation and promotion of tissue repair. Herein, we describe how cells that regulate these processes can be increased in prevalence at a site of disease or injury. We review several relevant cell therapy approaches as well as new strategies for directing endogenous regulatory cells capable of promoting environmental homeostasis and even the establishment of a pro-regenerative micro-environment. Collectively, these examples may provide a blueprint for next-generation "medicine" that spurs the body's own cells to action and replaces conventional drugs.
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Affiliation(s)
- Andrew J Glowacki
- Department of Chemical and Petroleum Engineering, University of Pittsburgh, Pittsburgh, PA, USA
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Hsu BB, Jamieson KS, Hagerman SR, Holler E, Ljubimova JY, Hammond PT. Ordered and kinetically discrete sequential protein release from biodegradable thin films. Angew Chem Int Ed Engl 2014; 53:8093-8. [PMID: 24938739 PMCID: PMC4387866 DOI: 10.1002/anie.201403702] [Citation(s) in RCA: 26] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/25/2014] [Indexed: 11/09/2022]
Abstract
Multidrug regimens can sometimes treat recalcitrant diseases when single-drug therapies fail. Recapitulating complex multidrug administration from controlled release films for localized delivery remains challenging because their release kinetics are frequently intertwined, and an initial burst release of each drug is usually uncontrollable. Kinetic control over protein release is demonstrated by cross-linking layer-by-layer films during the assembly process. We used biodegradable and naturally derived components and relied on copper-free click chemistry for bioorthogonal covalent cross-links throughout the film that entrap but do not modify the embedded protein. We found that this strategy restricted the interdiffusion of protein while maintaining its activity. By depositing a barrier layer and a second protein-containing layer atop this construct, we generated well-defined sequential protein release with minimal overlap that follows their spatial distribution within the film.
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Affiliation(s)
- Bryan B. Hsu
- Koch Institute for Integrative Cancer Research and the Institute for Soldier Nanotechnologies, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 USA, Department of Chemistry, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 USA
| | - Kelsey S. Jamieson
- Department of Chemical Engineering, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 USA
| | - Samantha R. Hagerman
- Department of Chemical Engineering, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 USA
| | - Eggehard Holler
- Nanomedicine Research Center; Department of Neurosurgery, Cedars Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048 USA
| | - Julia Y. Ljubimova
- Nanomedicine Research Center; Department of Neurosurgery, Cedars Sinai Medical Center, 8700 Beverly Boulevard, Los Angeles, CA 90048 USA
| | - Paula T. Hammond
- Koch Institute for Integrative Cancer Research and the Institute for Soldier Nanotechnologies, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 USA, Department of Chemical Engineering, Massachusetts Institute for Technology, 77 Massachusetts Avenue, Cambridge, MA 02139 USA
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Fu HL, Hong Y, Little SR, Wagner WR. Collagenase-Labile Polyurethane Urea Synthesis and Processing into Hollow Fiber Membranes. Biomacromolecules 2014; 15:2924-32. [DOI: 10.1021/bm500552f] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/29/2022]
Affiliation(s)
- Hui-Li Fu
- McGowan Institute for Regenerative Medicine, ‡Department of Surgery, §Department of Chemical & Petroleum Engineering, and ∥Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States
| | - Yi Hong
- McGowan Institute for Regenerative Medicine, ‡Department of Surgery, §Department of Chemical & Petroleum Engineering, and ∥Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States
| | - Steven R. Little
- McGowan Institute for Regenerative Medicine, ‡Department of Surgery, §Department of Chemical & Petroleum Engineering, and ∥Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States
| | - William R. Wagner
- McGowan Institute for Regenerative Medicine, ‡Department of Surgery, §Department of Chemical & Petroleum Engineering, and ∥Department of Bioengineering, University of Pittsburgh, Pittsburgh, Pennsylvania 15219, United States
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Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films. Angew Chem Int Ed Engl 2014. [DOI: 10.1002/ange.201403702] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 11/07/2022]
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Jiang B, Akar B, Waller T, Larson J, Appel A, Brey E. Design of a composite biomaterial system for tissue engineering applications. Acta Biomater 2014; 10:1177-86. [PMID: 24321351 DOI: 10.1016/j.actbio.2013.11.029] [Citation(s) in RCA: 43] [Impact Index Per Article: 3.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/29/2013] [Revised: 11/10/2013] [Accepted: 11/29/2013] [Indexed: 01/01/2023]
Abstract
Biomaterials that regulate vascularized tissue formation have the potential to contribute to new methods of tissue replacement and reconstruction. The goal of this study was to develop a porous, degradable tissue engineering scaffold that could deliver multiple growth factors and regulate vessel assembly within the porous structure of the material. Porous hydrogels of poly(ethylene glycol)-co-(L-lactic acid) (PEG-PLLA) were prepared via salt leaching. The degradation time of the hydrogels could be controlled between 1 and 7 weeks, based on hydrogel composition. Fibrin was incorporated into the interconnected pores of the hydrogels to promote neovascularization and as a reservoir for rapid (<5 days) growth factor delivery. Poly(lactic-co-glycolic acid) (PLGA) microspheres were incorporated into the degradable polymeric hydrogel scaffold to allow sustained (>30 days) growth factor delivery. Fibroblast growth factor-1 (FGF-1) and platelet-derived growth factor-BB (PDGF-BB) were delivered from the system owing to their roles in the promotion of angiogenesis and vascular stabilization, respectively. Hydrogels tested in vivo with a subcutaneous implantation model were selected based on the results from in vitro degradation and growth factor release kinetics. Dual growth factor delivery promoted significantly more tissue ingrowth in the scaffold compared with blank or single growth factor delivery. The sequential delivery of FGF-1 following PDGF-BB promoted more persistent and mature blood vessels. In conclusion, a biomaterials system was developed to provide structural support for tissue regeneration, as well as delivery of growth factors that stimulate neovascularization within the structure prior to complete degradation.
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Nelson DM, Hashizume R, Yoshizumi T, Blakney AK, Ma Z, Wagner WR. Intramyocardial injection of a synthetic hydrogel with delivery of bFGF and IGF1 in a rat model of ischemic cardiomyopathy. Biomacromolecules 2014; 15:1-11. [PMID: 24345287 DOI: 10.1021/bm4010639] [Citation(s) in RCA: 33] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/04/2023]
Abstract
It is increasingly appreciated that the properties of a biomaterial used in intramyocardial injection therapy influence the outcomes of infarcted hearts that are treated. In this report the extended in vivo efficacy of a thermally responsive material that can deliver dual growth factors while providing a slow degradation time and high mechanical stiffness is examined. Copolymers consisting of N-isopropylacrylamide, 2-hydroxyethyl methacrylate, and degradable methacrylate polylactide were synthesized. The release of bioactive basic fibroblast growth factor (bFGF) and insulin-like growth factor 1 (IGF1) from the gel and loaded poly(lactide-co-glycolide) microparticles was assessed. Hydrogel with or without loaded growth factors was injected into 2 week-old infarcts in Lewis rats and animals were followed for 16 weeks. The hydrogel released bioactive bFGF and IGF1 as shown by mitogenic effects on rat smooth muscle cells in vitro. Cardiac function and geometry were improved for 16 weeks after hydrogel injection compared to saline injection. Despite demonstrating that left ventricular levels of bFGF and IGF1 were elevated for two weeks after injection of growth factor loaded gels, both functional and histological assessment showed no added benefit to inclusion of these proteins. This result points to the complexity of designing appropriate materials for this application and suggests that the nature of the material alone, without exogenous growth factors, has a direct ability to influence cardiac remodeling.
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Affiliation(s)
- Devin M Nelson
- Department of Bioengineering and ‡McGowan Institute for Regenerative Medicine, University of Pittsburgh , Pittsburgh, Pennsylvania 15219, United States
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Browne S, Pandit A. Multi-modal delivery of therapeutics using biomaterial scaffolds. J Mater Chem B 2014; 2:6692-6707. [DOI: 10.1039/c4tb00863d] [Citation(s) in RCA: 32] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Functionalisation of biomaterials with therapeutic moieties (proteins, drugs, genes) is a pre-requisite to tissue regeneration and restoration of function following injury or disease.
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Affiliation(s)
- S. Browne
- Network of Excellence for Functional Biomaterials
- National University of Ireland
- Galway, Ireland
| | - A. Pandit
- Network of Excellence for Functional Biomaterials
- National University of Ireland
- Galway, Ireland
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