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Schlidt K, Asgardoon M, Febre-Alemañy DA, El-Mallah JC, Waldron O, Dawes J, Agrawal S, Landmesser ME, Ravnic DJ. Surgical Bioengineering of the Microvasculature and Challenges in Clinical Translation. TISSUE ENGINEERING. PART B, REVIEWS 2025. [PMID: 40171780 DOI: 10.1089/ten.teb.2024.0242] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 04/04/2025]
Abstract
Tissue and organ dysfunction are major causes of worldwide morbidity and mortality with all medical specialties being impacted. Tissue engineering is an interdisciplinary field relying on the combination of scaffolds, cells, and biologically active molecules to restore form and function. However, clinical translation is still largely hampered by limitations in vascularization. Consequently, a thorough understanding of the microvasculature is warranted. This review provides an overview of (1) angiogenesis, including sprouting angiogenesis, intussusceptive angiogenesis, vascular remodeling, vascular co-option, and inosculation; (2) strategies for vascularized engineered tissue fabrication such as scaffold modulation, prevascularization, growth factor utilization, and cell-based approaches; (3) guided microvascular development via scaffold modulation with electromechanical cues, 3D bioprinting, and electrospinning; (4) surgical approaches to bridge the micro- and macrovasculatures in order to hasten perfusion; and (5) building specific vasculature in the context of tissue repair and organ transplantation, including skin, adipose, bone, liver, kidney, and lung. Our goal is to provide the reader with a translational overview that spans developmental biology, tissue engineering, and clinical surgery.
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Affiliation(s)
- Kevin Schlidt
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Mohamadhossein Asgardoon
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - David A Febre-Alemañy
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Jessica C El-Mallah
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Olivia Waldron
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Jazzmyn Dawes
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Shailaja Agrawal
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Mary E Landmesser
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
| | - Dino J Ravnic
- Zubar Plastic Surgery Research Laboratory, Department of Surgery, Penn State Milton S. Hershey Medical Center, Hershey, Pennsylvania, USA
- Huck Institutes of the Life Sciences, The Pennsylvania State University, University Park, Pennsylvania, USA
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Pisani S, Evangelista A, Chesi L, Croce S, Avanzini MA, Dorati R, Genta I, Benazzo M, Comoli P, Conti B. Nanofibrous Scaffolds' Ability to Induce Mesenchymal Stem Cell Differentiation for Soft Tissue Regenerative Applications. Pharmaceuticals (Basel) 2025; 18:239. [PMID: 40006052 PMCID: PMC11859969 DOI: 10.3390/ph18020239] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/06/2025] [Revised: 01/27/2025] [Accepted: 02/07/2025] [Indexed: 02/27/2025] Open
Abstract
Mesenchymal stem cells (MSCs) have gained recognition as a highly versatile and promising cell source for repopulating bioengineered scaffolds due to their inherent capacity to differentiate into multiple cell types. However, MSC implantation techniques have often yielded inconsistent clinical results, underscoring the need for advanced approaches to enhance their therapeutic efficacy. Recent developments in three-dimensional (3D) bioengineered scaffolds have provided a significant breakthrough by closely mimicking the in vivo environment, addressing the limitations of traditional two-dimensional (2D) cell cultures. Among these, nanofibrous scaffolds have proven particularly effective, offering an optimal 3D framework, growth-permissive substrates, and the delivery of trophic factors crucial for MSC survival and regeneration. Furthermore, the selection of appropriate biomaterials can amplify the paracrine effects of MSCs, promoting both proliferation and targeted differentiation. The synergistic combination of MSCs with nanofibrous scaffolds has demonstrated remarkable potential in achieving repair, regeneration, and tissue-specific differentiation with enhanced safety and efficacy, paving the way for routine clinical applications. In this review, we examine the most recent studies (2013-2023) that explore the combined use of MSCs and nanofibrous scaffolds for differentiation into cardiogenic, epithelial, myogenic, tendon, and vascular cell lineages. Using PubMed, we identified and analyzed 275 relevant articles based on the search terms "Nanofibers", "Electrospinning", "Mesenchymal stem cells", and "Differentiation". This review highlights the critical advancements in the use of nanofibrous scaffolds as a platform for MSC differentiation and tissue regeneration. By summarizing key findings from the last decade, it provides valuable insights for researchers and clinicians aiming to optimize scaffold design, MSC integration, and translational applications. These insights could significantly influence future research directions and the development of more effective regenerative therapies.
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Affiliation(s)
- Silvia Pisani
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy; (L.C.); (R.D.); (I.G.); (B.C.)
| | - Aleksandra Evangelista
- Otorhinolaryngology Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (A.E.); (M.B.)
| | - Luca Chesi
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy; (L.C.); (R.D.); (I.G.); (B.C.)
| | - Stefania Croce
- Department of Clinical, Surgical, Diagnostic & Pediatric Sciences, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (S.C.); (M.A.A.); (P.C.)
| | - Maria Antonietta Avanzini
- Department of Clinical, Surgical, Diagnostic & Pediatric Sciences, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (S.C.); (M.A.A.); (P.C.)
| | - Rossella Dorati
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy; (L.C.); (R.D.); (I.G.); (B.C.)
| | - Ida Genta
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy; (L.C.); (R.D.); (I.G.); (B.C.)
| | - Marco Benazzo
- Otorhinolaryngology Unit, Department of Surgical Sciences, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (A.E.); (M.B.)
| | - Patrizia Comoli
- Department of Clinical, Surgical, Diagnostic & Pediatric Sciences, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy; (S.C.); (M.A.A.); (P.C.)
| | - Bice Conti
- Department of Drug Sciences, University of Pavia, 27100 Pavia, Italy; (L.C.); (R.D.); (I.G.); (B.C.)
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Mikaeeli Kangarshahi B, Naghib SM, Rabiee N. 3D printing and computer-aided design techniques for drug delivery scaffolds in tissue engineering. Expert Opin Drug Deliv 2024; 21:1615-1636. [PMID: 39323396 DOI: 10.1080/17425247.2024.2409913] [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: 01/20/2024] [Revised: 09/19/2024] [Accepted: 09/24/2024] [Indexed: 09/27/2024]
Abstract
INTRODUCTION The challenge in tissue engineering lies in replicating the intricate structure of the native extracellular matrix. Recent advancements in AM, notably 3D printing, offer unprecedented capabilities to tailor scaffolds precisely, controlling properties like structure and bioactivity. CAD tools complement this by facilitating design using patient-specific data. AREA’S COVERED This review introduces additive manufacturing (AM) and computer-aided design (CAD) as pivotal tools in advancing tissue engineering, particularly cartilage regeneration. This article explores various materials utilized in AM, focusing on polymers and hydrogels for their advantageous properties in tissue engineering applications. Integrating bioactive molecules, including growth factors, into scaffolds to promote tissue regeneration is discussed alongside strategies involving different cell sources, such as stem cells, to enhance tissue development within scaffold matrices. EXPERT OPINION Applications of AM and CAD in addressing specific challenges like osteochondral defects and osteoarthritis in cartilage tissue engineering are highlighted. This review consolidates current research findings, offering expert insights into the evolving landscape of AM and CAD technologies in advancing tissue engineering, particularly in cartilage regeneration.
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Affiliation(s)
- Babak Mikaeeli Kangarshahi
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology, Tehran, Iran
| | - Seyed Morteza Naghib
- Nanotechnology Department, School of Advanced Technologies, Iran University of Science and Technology, Tehran, Iran
| | - Navid Rabiee
- Department of Biomaterials, Saveetha Dental College and Hospitals, SIMATS, Saveetha University, Chennai, India
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Eivazi Zadeh Z, Nour S, Kianersi S, Jonidi Shariatzadeh F, Williams RJ, Nisbet DR, Bruggeman KF. Mining human clinical waste as a rich source of stem cells for neural regeneration. iScience 2024; 27:110307. [PMID: 39156636 PMCID: PMC11326931 DOI: 10.1016/j.isci.2024.110307] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 08/20/2024] Open
Abstract
Neural diseases are challenging to treat and are regarded as one of the major causes of disability and morbidity in the world. Stem cells can provide a solution, by offering a mechanism to replace damaged circuitry. However, obtaining sufficient cell sources for neural regeneration remains a significant challenge. In recent years, waste-derived stem(-like) cells (WDS-lCs) extracted from both prenatal and adult clinical waste tissues/products, have gained increasing attention for application in neural tissue repair and remodeling. This often-overlooked pool of cells possesses favorable characteristics; including self-renewal, neural differentiation, secretion of neurogenic factors, cost-effectiveness, and low ethical concerns. Here, we offer a perspective regarding the biological properties, extraction protocols, and preclinical and clinical treatments where prenatal and adult WDS-lCs have been utilized for cell replacement therapy in neural applications, and the challenges involved in optimizing these approaches toward patient led therapies.
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Affiliation(s)
- Zahra Eivazi Zadeh
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
| | - Shirin Nour
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- Polymer Science Group, Department of Chemical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
| | - Sogol Kianersi
- Science Foundation Ireland (SFI) Centre for Research in Medical Devices (CÚRAM), Biomedical Sciences, University of Galway, Galway, Ireland
| | | | - Richard J. Williams
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- iMPACT, School of Medicine, Deakin University, Waurn Ponds, VIC 3216, Australia
| | - David R. Nisbet
- Department of Biomedical Engineering, University of Melbourne, Parkville, VIC 3010, Australia
- The Graeme Clark Institute, University of Melbourne, Melbourne, VIC, Australia
- ACRF Department of Cancer Biology and Therapeutics, The John Curtin School of Medical Research, ANU College of Health & Medicine, Canberra, ACT, Australia
- Research School of Chemistry, ANU College of Science, Canberra, ACT, Australia
- Melbourne Medical School, Faculty of Medicine, Dentistry and Health Science, The University of Melbourne, Melbourne, VIC, Australia
- Founder and Scientific Advisory of Nano Status, Building 137, Sullivans Creek Rd, ANU, Acton, Canberra, ACT, Australia
| | - Kiara F. Bruggeman
- Laboratory of Advanced Biomaterials Research, School of Engineering, Australian National University, Canberra, ACT, Australia
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Luo Y. Toward Fully Automated Personalized Orthopedic Treatments: Innovations and Interdisciplinary Gaps. Bioengineering (Basel) 2024; 11:817. [PMID: 39199775 PMCID: PMC11351140 DOI: 10.3390/bioengineering11080817] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/10/2024] [Revised: 08/04/2024] [Accepted: 08/09/2024] [Indexed: 09/01/2024] Open
Abstract
Personalized orthopedic devices are increasingly favored for their potential to enhance long-term treatment success. Despite significant advancements across various disciplines, the seamless integration and full automation of personalized orthopedic treatments remain elusive. This paper identifies key interdisciplinary gaps in integrating and automating advanced technologies for personalized orthopedic treatment. It begins by outlining the standard clinical practices in orthopedic treatments and the extent of personalization achievable. The paper then explores recent innovations in artificial intelligence, biomaterials, genomic and proteomic analyses, lab-on-a-chip, medical imaging, image-based biomechanical finite element modeling, biomimicry, 3D printing and bioprinting, and implantable sensors, emphasizing their contributions to personalized treatments. Tentative strategies or solutions are proposed to address the interdisciplinary gaps by utilizing innovative technologies. The key findings highlight the need for the non-invasive quantitative assessment of bone quality, patient-specific biocompatibility, and device designs that address individual biological and mechanical conditions. This comprehensive review underscores the transformative potential of these technologies and the importance of multidisciplinary collaboration to integrate and automate them into a cohesive, intelligent system for personalized orthopedic treatments.
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Affiliation(s)
- Yunhua Luo
- Department of Mechanical Engineering, University of Manitoba, Winnipeg, MB R3T 2N2, Canada;
- Biomedical Engineering (Graduate Program), University of Manitoba, Winnipeg, MB R3T 2N2, Canada
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Kumari J, Hammink R, Baaij J, Wagener FADTG, Kouwer PHJ. Antifibrotic properties of hyaluronic acid crosslinked polyisocyanide hydrogels. BIOMATERIALS ADVANCES 2024; 156:213705. [PMID: 38006784 DOI: 10.1016/j.bioadv.2023.213705] [Citation(s) in RCA: 3] [Impact Index Per Article: 3.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/22/2023] [Revised: 11/20/2023] [Accepted: 11/21/2023] [Indexed: 11/27/2023]
Abstract
Fibrosis is characterized by the formation of fibrous connective tissue in response to primary injury. As a result, an affected organ may lose part of its functionality due to chronic, organ-specific tissue damage. Since fibrosis is a leading cause of death worldwide, targeting fibrotic diseases with antifibrotic hydrogels can be a lifesaving therapeutic strategy. This study developed a novel hybrid antifibrotic hydrogel by combining the synthetic polyisocyanide (PIC) with hyaluronic acid (HA). Gels of PIC are highly tailorable, thermosensitive, and strongly biomimetic in architecture and mechanical properties, whereas HA is known to promote non-fibrotic fetal wound healing and inhibits inflammatory signaling. The developed HA-PIC hybrids were biocompatible with physical properties comparable to those of the PIC gels. The antifibrotic nature of the gels was assessed by 3D cultures of human foreskin fibroblasts in the presence (or absence as control) of TGFβ1 that promotes differentiation into myofibroblasts, a critical step in fibrosis. Proliferation and macroscopic contraction assays and studies on the formation of stress fibers and characteristic fibrosis markers all indicate a strong antifibrotic nature of HA-PIC hydrogel. We showed that these effects originate from both the lightly crosslinked architecture and the presence of HA itself. The hybrid displaying both these effects shows the strongest antifibrotic nature and is a promising candidate for use as in vivo treatment for skin fibrosis.
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Affiliation(s)
- Jyoti Kumari
- Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands; Department of Dentistry - Orthodontics and Craniofacial Biology, Radboud University Medical Centre, 6525 EX Nijmegen, the Netherlands
| | - Roel Hammink
- Department of Tumor Immunology, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands; Division of Immunotherapy, Oncode Institute, Radboud University Medical Center, 6525 GA Nijmegen, the Netherlands
| | - Jochem Baaij
- Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands
| | - Frank A D T G Wagener
- Department of Dentistry - Orthodontics and Craniofacial Biology, Radboud University Medical Centre, 6525 EX Nijmegen, the Netherlands.
| | - Paul H J Kouwer
- Institute for Molecules and Materials, Radboud University, Heyendaalseweg 135, 6525 AJ Nijmegen, the Netherlands.
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Vafa E, Tayebi L, Abbasi M, Azizli MJ, Bazargan-Lari R, Talaiekhozani A, Zareshahrabadi Z, Vaez A, Amani AM, Kamyab H, Chelliapan S. A better roadmap for designing novel bioactive glasses: effective approaches for the development of innovative revolutionary bioglasses for future biomedical applications. ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH INTERNATIONAL 2023; 30:116960-116983. [PMID: 36456674 DOI: 10.1007/s11356-022-24176-1] [Citation(s) in RCA: 16] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 08/27/2022] [Accepted: 11/08/2022] [Indexed: 06/17/2023]
Abstract
The introduction of bioactive glasses (BGs) precipitated a paradigm shift in the medical industry and opened the path for the development of contemporary regenerative medicine driven by biomaterials. This composition can bond to live bone and can induce osteogenesis by the release of physiologically active ions. 45S5 BG products have been transplanted effectively into millions of patients around the world, primarily to repair bone and dental defects. Over the years, many other BG compositions have been introduced as innovative biomaterials for repairing soft tissue and delivering drugs. When research first started, many of the accomplishments that have been made today were unimaginable. It appears that the true capacity of BGs has not yet been realized. Because of this, research involving BGs is extremely fascinating. However, to be successful, it requires interdisciplinary cooperation between physicians, glass chemists, and bioengineers. The present paper gives a picture of the existing clinical uses of BGs and illustrates key difficulties deserving to be faced in the future. The challenges range from the potential for BGs to be used in a wide variety of applications. We have high hopes that this paper will be of use to both novice researchers, who are just beginning their journey into the world of BGs, as well as seasoned scientists, in that it will promote conversation regarding potential additional investigation and lead to the discovery of innovative medical applications for BGs.
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Affiliation(s)
- Ehsan Vafa
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Lobat Tayebi
- Marquette University School of Dentistry, Milwaukee, WI, USA
| | - Milad Abbasi
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Mohammad Javad Azizli
- Department of Chemistry and Chemical Engineering, Islamic Azad University, Rasht, Rasht Branch, Iran
| | - Reza Bazargan-Lari
- Department of Materials Science and Engineering, Marvdasht Branch, Islamic Azad University, Marvdasht, Iran
| | - Amirreza Talaiekhozani
- Department of Civil Engineering, Jami Institute of Technology, Isfahan, Iran
- Alavi Educational and Cultural Complex, Shiraz, Iran
| | - Zahra Zareshahrabadi
- Basic Sciences in Infectious Diseases Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Ahmad Vaez
- Department of Tissue Engineering and Applied Cell Sciences, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran.
| | - Ali Mohamad Amani
- Department of Medical Nanotechnology, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Hesam Kamyab
- Malaysia-Japan International Institute of Technology, Universiti Teknologi Malaysia, Jalan Sultan Yahya Petra, 54100, Kuala Lumpur, Malaysia
- Department of Biomaterials, Saveetha Dental College and Hospital, Saveetha Institute of Medical and Technical Sciences, Chennai 600077, India, Chennai, India
| | - Shreeshivadasan Chelliapan
- Engineering Department, Razak Faculty of Technology & Informatics, Universiti Teknologi Malaysia, Jalan Sultan Yahya Petra, 54100, Kuala Lumpur, Malaysia
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Pisani S, Mauri V, Negrello E, Friuli V, Genta I, Dorati R, Bruni G, Marconi S, Auricchio F, Pietrabissa A, Benazzo M, Conti B. Hybrid 3D-Printed and Electrospun Scaffolds Loaded with Dexamethasone for Soft Tissue Applications. Pharmaceutics 2023; 15:2478. [PMID: 37896239 PMCID: PMC10609822 DOI: 10.3390/pharmaceutics15102478] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/07/2023] [Revised: 09/01/2023] [Accepted: 09/28/2023] [Indexed: 10/29/2023] Open
Abstract
BACKGROUND To make the regenerative process more effective and efficient, tissue engineering (TE) strategies have been implemented. Three-dimensional scaffolds (electrospun or 3D-printed), due to their suitable designed architecture, offer the proper location of the position of cells, as well as cell adhesion and the deposition of the extracellular matrix. Moreover, the possibility to guarantee a concomitant release of drugs can promote tissue regeneration. METHODS A PLA/PCL copolymer was used for the manufacturing of electrospun and hybrid scaffolds (composed of a 3D-printed support coated with electrospun fibers). Dexamethasone was loaded as an anti-inflammatory drug into the electrospun fibers, and the drug release kinetics and scaffold biological behavior were evaluated. RESULTS The encapsulation efficiency (EE%) was higher than 80%. DXM embedding into the electrospun fibers resulted in a slowed drug release rate, and a slower release was seen in the hybrid scaffolds. The fibers maintained their nanometric dimensions (less than 800 nm) even after deposition on the 3D-printed supports. Cell adhesion and proliferation was favored in the DXM-loading hybrid scaffolds. CONCLUSIONS The hybrid scaffolds that were developed in this study can be optimized as a versatile platform for soft tissue regeneration.
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Affiliation(s)
- Silvia Pisani
- Department of Drug Sciences, University of Pavia, Viale Taramelli, 12, 27100 Pavia, Italy; (V.F.); (I.G.); (R.D.); (B.C.)
| | - Valeria Mauri
- SC General Surgery 2, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy; (V.M.); (E.N.); (A.P.)
| | - Erika Negrello
- SC General Surgery 2, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy; (V.M.); (E.N.); (A.P.)
| | - Valeria Friuli
- Department of Drug Sciences, University of Pavia, Viale Taramelli, 12, 27100 Pavia, Italy; (V.F.); (I.G.); (R.D.); (B.C.)
| | - Ida Genta
- Department of Drug Sciences, University of Pavia, Viale Taramelli, 12, 27100 Pavia, Italy; (V.F.); (I.G.); (R.D.); (B.C.)
| | - Rossella Dorati
- Department of Drug Sciences, University of Pavia, Viale Taramelli, 12, 27100 Pavia, Italy; (V.F.); (I.G.); (R.D.); (B.C.)
| | - Giovanna Bruni
- Consorzio per lo Sviluppo dei Sistemi a Grande Interfase (C.S.G.I.), Department of Chemistry, Physical Chemistry Section, University of Pavia, 27100 Pavia, Italy;
| | - Stefania Marconi
- Department of Civil Engineering and Architecture, University of Pavia, 27100 Pavia, Italy;
- Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy;
| | - Ferdinando Auricchio
- Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy;
| | - Andrea Pietrabissa
- SC General Surgery 2, Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy; (V.M.); (E.N.); (A.P.)
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy;
| | - Marco Benazzo
- Department of Clinical, Surgical, Diagnostic and Pediatric Sciences, University of Pavia, 27100 Pavia, Italy;
- Department of Otorhinolaryngology, Fondazione IRCCS Policlinico San Matteo, 27100 Pavia, Italy
- Integrated Unit of Experimental Surgery, Advanced Microsurgery and Regenerative Medicine, Università degli Studi di Pavia, 27100 Pavia, Italy
| | - Bice Conti
- Department of Drug Sciences, University of Pavia, Viale Taramelli, 12, 27100 Pavia, Italy; (V.F.); (I.G.); (R.D.); (B.C.)
- Fondazione IRCCS Policlinico San Matteo, Viale Camillo Golgi, 19, 27100 Pavia, Italy;
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Design of Functional RGD Peptide-Based Biomaterials for Tissue Engineering. Pharmaceutics 2023; 15:pharmaceutics15020345. [PMID: 36839667 PMCID: PMC9967156 DOI: 10.3390/pharmaceutics15020345] [Citation(s) in RCA: 27] [Impact Index Per Article: 13.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/29/2022] [Revised: 01/16/2023] [Accepted: 01/18/2023] [Indexed: 01/22/2023] Open
Abstract
Tissue engineering (TE) is a rapidly expanding field aimed at restoring or replacing damaged tissues. In spite of significant advancements, the implementation of TE technologies requires the development of novel, highly biocompatible three-dimensional tissue structures. In this regard, the use of peptide self-assembly is an effective method for developing various tissue structures and surface functionalities. Specifically, the arginine-glycine-aspartic acid (RGD) family of peptides is known to be the most prominent ligand for extracellular integrin receptors. Due to their specific expression patterns in various human tissues and their tight association with various pathophysiological conditions, RGD peptides are suitable targets for tissue regeneration and treatment as well as organ replacement. Therefore, RGD-based ligands have been widely used in biomedical research. This review article summarizes the progress made in the application of RGD for tissue and organ development. Furthermore, we examine the effect of RGD peptide structure and sequence on the efficacy of TE in clinical and preclinical studies. Additionally, we outline the recent advancement in the use of RGD functionalized biomaterials for the regeneration of various tissues, including corneal repair, artificial neovascularization, and bone TE.
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Ye D, Sun Y, Yang L, Su J. An investigation of a self-assembled cell-extracellular complex and its potentials in improving wound healing. J Appl Biomater Funct Mater 2023; 21:22808000221130168. [PMID: 36633288 DOI: 10.1177/22808000221130168] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/13/2023] Open
Abstract
BACKGROUND To maintain and enhance the wound healing effects of mesenchymal stem cells (MSCs), a scaffold for hosting MSCs is needed, which ought to be completely biocompatible, durable, producible, and of human source. OBJECTIVE To build a cell-extracellular matrix (ECM) complex assembled by human umbilical cord mesenchymal stem cells (HuMSCs) and to investigate its clinical potentials in promoting wound healing. METHOD HuMSCs were isolated and expanded. When the cells of third passage reached confluency, ascorbic acid was added to stimulate the cells to deposit ECM where the cells grew in. Four weeks later, a cells-loaded ECM sheet was formed. The cell-ECM complex was observed under the scanning electron microscopy (SEM) and subjected to histological studies. The supernatants were collected and the cell-ECM complex was harvested at different time points and processed for enzyme-linked immune sorbent assay (ELISA) and mRNA analysis. The in vivo experiments were performed by means of implanting the cell-ECM complex on the mice back for up to 6 months and the specimens were collected for histological studies. RESULTS After 4 weeks of cultivation with ascorbic stimulation, a sheet was formed which is mainly composed with HuMSCs, collagen and hyaluronic acid. The cell-ECM complex can sustain to certain tensile force. The mRNA and protein levels of vascular endothelial growth factor-α (VEGF-α), hepatocyte growth factor (HGF), keratinocyte growth factor (KGF), and transforming growth factor-β1 (TGF-β1) were remarkably increased compared to monolayer-cultured cells. The implanted cell-ECM complex on mice was still noticeable with host cells infiltration and vascularization on 6 months. CONCLUSION Our studies suggested that HuMSCs can be multi-cultivated through adding ascorbic stimulation and ECM containing collagen and hyaluronic acid were enriched around the cells which self-assembly formed a cell-ECM complex. Cell-ECM complex can improve growth factors secretion remarkably which means it may promote wound healing by paracrine.
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Affiliation(s)
- Danyan Ye
- Research Center for Translational Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China
| | - Yaowen Sun
- Department of Burns and Plastic Surgery, Shaanxi Provincial People's Hospital, Xi'an, PR China
| | - Lujun Yang
- Research Center for Translational Medicine, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China
- Department of Plastic Surgery and Burn Center, Second Affiliated Hospital of Shantou University Medical College, Shantou, Guangdong, PR China
| | - Jing Su
- Nursing Department, Shantou University Medical College, Shantou, Guangdong, PR China
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11
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Iravani S, Varma RS. Cellulose-Based Composites as Scaffolds for Tissue Engineering: Recent Advances. MOLECULES (BASEL, SWITZERLAND) 2022; 27:molecules27248830. [PMID: 36557963 PMCID: PMC9784432 DOI: 10.3390/molecules27248830] [Citation(s) in RCA: 6] [Impact Index Per Article: 2.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2022] [Revised: 12/06/2022] [Accepted: 12/09/2022] [Indexed: 12/15/2022]
Abstract
Today, numerous studies have focused on the design of novel scaffolds for tissue engineering and regenerative medicine applications; however, several challenges still exist in terms of biocompatibility/cytocompatibility, degradability, cell attachment/proliferation, nutrient diffusion, large-scale production, and clinical translation studies. Greener and safer technologies can help to produce scaffolds with the benefits of cost-effectiveness, high biocompatibility, and biorenewability/sustainability, reducing their toxicity and possible side effects. However, some challenges persist regarding their degradability, purity, having enough porosity, and possible immunogenicity. In this context, naturally derived cellulose-based scaffolds with high biocompatibility, ease of production, availability, sustainability/renewability, and environmentally benign attributes can be applied for designing scaffolds. These cellulose-based scaffolds have shown unique mechanical properties, improved cell attachment/proliferation, multifunctionality, and enhanced biocompatibility/cytocompatibility, which make them promising candidates for tissue engineering applications. Herein, the salient developments pertaining to cellulose-based scaffolds for neural, bone, cardiovascular, and skin tissue engineering are deliberated, focusing on the challenges and opportunities.
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Affiliation(s)
- Siavash Iravani
- Faculty of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan 81746-73461, Iran
- Correspondence: (S.I.); (R.S.V.)
| | - Rajender S. Varma
- Regional Centre of Advanced Technologies and Materials, Czech Advanced Technology and Research Institute, Palacký University in Olomouc, Šlechtitelů 27, 783 71 Olomouc, Czech Republic
- Correspondence: (S.I.); (R.S.V.)
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12
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In vitro evaluation of modified halloysite nanotubes with sodium alginate-reinforced PVA/PVP nanocomposite films for tissue engineering applications. APPLIED NANOSCIENCE 2022. [DOI: 10.1007/s13204-022-02684-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 11/09/2022]
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13
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Recent Advances of Chitosan Formulations in Biomedical Applications. Int J Mol Sci 2022; 23:ijms231810975. [PMID: 36142887 PMCID: PMC9504745 DOI: 10.3390/ijms231810975] [Citation(s) in RCA: 106] [Impact Index Per Article: 35.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/24/2022] [Revised: 09/12/2022] [Accepted: 09/13/2022] [Indexed: 02/07/2023] Open
Abstract
Chitosan, a naturally abundant cationic polymer, is chemically composed of cellulose-based biopolymers derived by deacetylating chitin. It offers several attractive characteristics such as renewability, hydrophilicity, biodegradability, biocompatibility, non-toxicity, and a broad spectrum of antimicrobial activity towards gram-positive and gram-negative bacteria as well as fungi, etc., because of which it is receiving immense attention as a biopolymer for a plethora of applications including drug delivery, protective coating materials, food packaging films, wastewater treatment, and so on. Additionally, its structure carries reactive functional groups that enable several reactions and electrochemical interactions at the biomolecular level and improves the chitosan’s physicochemical properties and functionality. This review article highlights the extensive research about the properties, extraction techniques, and recent developments of chitosan-based composites for drug, gene, protein, and vaccine delivery applications. Its versatile applications in tissue engineering and wound healing are also discussed. Finally, the challenges and future perspectives for chitosan in biomedical applications are elucidated.
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14
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Bucciarelli A, Motta A. Use of Bombyx mori silk fibroin in tissue engineering: From cocoons to medical devices, challenges, and future perspectives. BIOMATERIALS ADVANCES 2022; 139:212982. [PMID: 35882138 DOI: 10.1016/j.bioadv.2022.212982] [Citation(s) in RCA: 42] [Impact Index Per Article: 14.0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 02/28/2022] [Revised: 06/07/2022] [Accepted: 06/08/2022] [Indexed: 05/26/2023]
Abstract
Silk fibroin has become a prominent material in tissue engineering (TE) over the last 20 years with almost 10,000 published works spanning in all the TE applications, from skeleton to neuronal regeneration. Fibroin is an extremely versatile biopolymer that, due to its ease of processing, has enabled the development of an entire plethora of materials whose properties and architectures can be tailored to suit target applications. Although the research and development of fibroin TE materials and devices is mature, apart from sutures, only a few medical products made of fibroin are used in the clinical routines. <40 clinical trials of Bombyx mori silk-related products have been reported by the FDA and few of them resulted in a commercialized device. In this review, after explaining the structure and properties of silk fibroin, we provide an overview of both fibroin constructs existing in the literature and fibroin devices used in clinic. Through the comparison of these two categories, we identified the burning issues faced by fibroin products during their translation to the market. Two main aspects will be considered. The first is the standardization of production processes, which leads both to the standardization of the characteristics of the issued device and the correct assessment of its failure. The second is the FDA regulations, which allow new devices to be marketed through the 510(k) clearance by demonstrating their equivalence to a commercialized medical product. The history of some fibroin medical devices will be taken as a case study. Finally, we will outline a roadmap outlining what actions we believe are needed to bring fibroin products to the market.
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Affiliation(s)
- Alessio Bucciarelli
- CNR nanotech, National Council of Research, University Campus Ecotekne, Via Monteroni, 73100 Lecce, Italy.
| | - Antonella Motta
- BIOtech research centre and European Institute of Excellence on Tissue Engineering and Regenerative Medicine, Department of Industrial Engineering, University of Trento, Via delle Regole 101, 38123 Trento, Italy.
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15
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Crossing Phylums: Butterfly Wing as a Natural Perfusable Three-Dimensional (3D) Bioconstruct for Bone Tissue Engineering. J Funct Biomater 2022; 13:jfb13020068. [PMID: 35735923 PMCID: PMC9225241 DOI: 10.3390/jfb13020068] [Citation(s) in RCA: 3] [Impact Index Per Article: 1.0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/07/2022] [Revised: 05/17/2022] [Accepted: 05/25/2022] [Indexed: 12/02/2022] Open
Abstract
Despite the advent of promising technologies in tissue engineering, finding a biomimetic 3D bio-construct capable of enhancing cell attachment, maintenance, and function is still a challenge in producing tailorable scaffolds for bone regeneration. Here, osteostimulatory effects of the butterfly wings as a naturally porous and non-toxic chitinous scaffold on mesenchymal stromal cells are assessed. The topographical characterization of the butterfly wings implied their ability to mimic bone tissue microenvironment, whereas their regenerative potential was validated after a 14-day cell culture. In vivo analysis showed that the scaffold induced no major inflammatory response in Wistar rats. Topographical features of the bioconstruct upregulated the osteogenic genes, including COL1A1, ALP, BGLAP, SPP1, SP7, and AML3 in differentiated cells compared to the cells cultured in the culture plate. However, butterfly wings were shown to provide a biomimetic microstructure and proper bone regenerative capacity through a unique combination of various structural and material properties. Therefore, this novel platform can be confidently recommended for bone tissue engineering applications.
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16
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Karoichan A, Baudequin T, Al-Jallad H, Tabrizian M. Encapsulation and differentiation of adipose-derived mesenchymal stem cells in a biomimetic purine cross-linked chitosan sponge. J Biomed Mater Res A 2021; 110:585-594. [PMID: 34545996 DOI: 10.1002/jbm.a.37311] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/21/2021] [Revised: 08/19/2021] [Accepted: 09/07/2021] [Indexed: 12/11/2022]
Abstract
Mesenchymal stem cells derived from adipose tissue have become a widely investigated cell source to use in tissue engineering applications. However, an optimal delivery scaffold for these cells is still needed. A rapidly gelling, injectable chitosan sponge was proposed in this study as a potential candidate for a suitable delivery scaffold. The results demonstrated the ability to encapsulate the stem cells at a 97.6% encapsulation efficiency and that the cells maintain their viability within the sponge. With the potential of using this scaffold for bone tissue engineering, ALP activity assay and fluorescent imaging for osteocalcin proved the ability to differentiate the encapsulated cells into the osteogenic lineage. Furthermore, co-encapsulation of pyrophosphatase within the sponge was investigated as a method to overcome the inhibitory effects that the sponge degradation by-products have on mineralization. Alizarin Red S staining demonstrated the beneficial effects of adding pyrophosphatase, where a significant increase in mineralization levels was achieved.
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Affiliation(s)
- Antoine Karoichan
- Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.,Shriners Hospitals for Children, Montreal, Quebec, Canada
| | - Timothée Baudequin
- Biomedical Engineering Department, McGill University, Montreal, Quebec, Canada
| | - Hadil Al-Jallad
- Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.,Shriners Hospitals for Children, Montreal, Quebec, Canada.,Department of Experimental Surgery, McGill University, Montreal, Quebec, Canada
| | - Maryam Tabrizian
- Faculty of Dentistry, McGill University, Montreal, Quebec, Canada.,Biomedical Engineering Department, McGill University, Montreal, Quebec, Canada
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17
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Akarapipad P, Kaarj K, Liang Y, Yoon JY. Environmental Toxicology Assays Using Organ-on-Chip. ANNUAL REVIEW OF ANALYTICAL CHEMISTRY (PALO ALTO, CALIF.) 2021; 14:155-183. [PMID: 33974806 DOI: 10.1146/annurev-anchem-091620-091335] [Citation(s) in RCA: 14] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 06/12/2023]
Abstract
Adverse effects of environmental toxicants to human health have traditionally been assayed using in vitro assays. Organ-on-chip (OOC) is a new platform that can bridge the gaps between in vitro assays (or 3D cell culture) and animal tests. Microenvironments, physical and biochemical stimuli, and adequate sensing and biosensing systems can be integrated into OOC devices to better recapitulate the in vivo tissue and organ behavior and metabolism. While OOCs have extensively been studied for drug toxicity screening, their implementation in environmental toxicology assays is minimal and has limitations. In this review, recent attempts of environmental toxicology assays using OOCs, including multiple-organs-on-chip, are summarized and compared with OOC-based drug toxicity screening. Requirements for further improvements are identified and potential solutions are suggested.
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Affiliation(s)
- Patarajarin Akarapipad
- Department of Biomedical Engineering, University of Arizona, Tucson, Arizona 85721, USA;
| | - Kattika Kaarj
- Department of Biosystems Engineering, University of Arizona, Tucson, Arizona 85721, USA
| | - Yan Liang
- Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA
| | - Jeong-Yeol Yoon
- Department of Biomedical Engineering, University of Arizona, Tucson, Arizona 85721, USA;
- Department of Biosystems Engineering, University of Arizona, Tucson, Arizona 85721, USA
- Department of Chemistry and Biochemistry, University of Arizona, Tucson, Arizona 85721, USA
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18
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Liu W, Shi K, Zhu X, Zhao H, Zhang H, Jones A, Liu L, Li G. Adipose Tissue-derived Stem cells in Plastic and Reconstructive Surgery: A Bibliometric Study. Aesthetic Plast Surg 2021; 45:679-689. [PMID: 31980863 DOI: 10.1007/s00266-020-01615-3] [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: 10/31/2019] [Accepted: 01/02/2020] [Indexed: 12/11/2022]
Abstract
BACKGROUND Due to the evolving nature of the applications of adipose tissue-derived stem cells (ADSCs) and the rapidly growing body of scientific literature, it is difficult to generate a manual compilation and systematic review of ADSCs in plastic and reconstructive surgery. METHODS Bibliographic records were retrieved from the Web of Science Core Collection and analyzed with CiteSpace. RESULTS We retrieved 691 publications and their references. We identified 52 research categories. Interdisciplinary studies were common. The journals clustered into 13 subnetworks. The top institutions were Stanford University; University of Pittsburgh; University of Tokyo; University of California, Los Angeles; University of California, Davis; New York University; Tulane University; and University of Michigan. National Institutes of Health and National Natural Science Foundation of China provided the most generous financial support. Studies clustered into 22 topics. Emerging trends may include improvement of fat grafting, and application of ADSCs in wound healing, scleroderma, and facial rejuvenation. CONCLUSION The present study provides a panoramic view of ADSCs in plastic and reconstructive surgery. Analysis of journals, institutions, and grants could help researchers in different ways. Researchers may consider the emerging trends when deciding the direction of their study. LEVEL OF EVIDENCE III This journal requires that authors assign a level of evidence to each article. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266 .
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Affiliation(s)
- Wenhui Liu
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Ke Shi
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Xuran Zhu
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Hongyan Zhao
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Hui Zhang
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Andrew Jones
- Center for Regenerative Medicine, Oregon Health and Science University, Portland, 97239, USA
| | - Linbo Liu
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China
| | - Guangshuai Li
- Department of Plastic Surgery, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China.
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19
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Granz CL, Gorji A. Dental stem cells: The role of biomaterials and scaffolds in developing novel therapeutic strategies. World J Stem Cells 2020; 12:897-921. [PMID: 33033554 PMCID: PMC7524692 DOI: 10.4252/wjsc.v12.i9.897] [Citation(s) in RCA: 31] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/04/2020] [Revised: 06/05/2020] [Accepted: 08/16/2020] [Indexed: 02/06/2023] Open
Abstract
Dental stem cells (DSCs) are self-renewable cells that can be obtained easily from dental tissues, and are a desirable source of autologous stem cells. The use of DSCs for stem cell transplantation therapeutic approaches is attractive due to their simple isolation, high plasticity, immunomodulatory properties, and multipotential abilities. Using appropriate scaffolds loaded with favorable biomolecules, such as growth factors, and cytokines, can improve the proliferation, differentiation, migration, and functional capacity of DSCs and can optimize the cellular morphology to build tissue constructs for specific purposes. An enormous variety of scaffolds have been used for tissue engineering with DSCs. Of these, the scaffolds that particularly mimic tissue-specific micromilieu and loaded with biomolecules favorably regulate angiogenesis, cell-matrix interactions, degradation of extracellular matrix, organized matrix formation, and the mineralization abilities of DSCs in both in vitro and in vivo conditions. DSCs represent a promising cell source for tissue engineering, especially for tooth, bone, and neural tissue restoration. The purpose of the present review is to summarize the current developments in the major scaffolding approaches as crucial guidelines for tissue engineering using DSCs and compare their effects in tissue and organ regeneration.
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Affiliation(s)
- Cornelia Larissa Granz
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
| | - Ali Gorji
- Epilepsy Research Center, Westfälische Wilhelms-Universität Münster, Münster 48149, Germany
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20
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Debnath T, Mallarpu CS, Chelluri LK. Development of Bioengineered Organ Using Biological Acellular Rat Liver Scaffold and Hepatocytes. Organogenesis 2020; 16:61-72. [PMID: 32362216 DOI: 10.1080/15476278.2020.1742534] [Citation(s) in RCA: 21] [Impact Index Per Article: 4.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 01/01/2023] Open
Abstract
The increasing demand for organs for transplantation necessitates the development of substitutes to meet the structural and physiological functions. Tissue decellularization and recellularization aids in retaining the three-dimensional integrity, biochemical composition, tissue ultra-structure, and mechanical behavior, which makes them functionally suitable for organ transplantation. Herein, we attempted to rebuild functional liver grafts in small animal model (Wistar rat) with a potential of translation. A soft approach was adopted using 0.1% SDS (Sodium Dodecyl Sulfate) for decellularization and primary hepatocytes were used as a potential cell source for recellularization. The decellularization process was evaluated and confirmed using histology, DNA content, ultra-structure analysis. The resultant scaffold was re-seeded with the rat hepatocytes and their biocompatibility was assessed by its metabolic functions and gene expression. The structural components of the Extracellular matrix (ECM) (Laminins, Collagen type I, Reticulins) were conserved and the liver cell-specific proteins like CK-18, alpha-fetoprotein, albumin were expressed in the recellularized scaffold. The functionality and metabolic activity of the repopulated scaffold were evident from the albumin and urea production. Expression of Cytokeratin-19 (CK-19), Glucose 6-Phosphatase (G6P), Albumin, Gamma Glutamyl Transferase (GGT) genes has distinctly confirmed the translational signals after the repopulation process. Our study clearly elucidates that the native extracellular matrix of rat liver can be utilized as a scaffold for effective recellularization for whole organ regeneration.
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Affiliation(s)
- Tanya Debnath
- Stem Cell Unit, Global Medical Education & Research Foundation , Hyderabad, India
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21
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Merckx G, Tay H, Lo Monaco M, van Zandvoort M, De Spiegelaere W, Lambrichts I, Bronckaers A. Chorioallantoic Membrane Assay as Model for Angiogenesis in Tissue Engineering: Focus on Stem Cells. TISSUE ENGINEERING PART B-REVIEWS 2020; 26:519-539. [PMID: 32220219 DOI: 10.1089/ten.teb.2020.0048] [Citation(s) in RCA: 40] [Impact Index Per Article: 8.0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 12/12/2022]
Abstract
Tissue engineering aims to structurally and functionally regenerate damaged tissues, which requires the formation of new blood vessels that supply oxygen and nutrients by the process of angiogenesis. Stem cells are a promising tool in regenerative medicine due to their combined differentiation and paracrine angiogenic capacities. The study of their proangiogenic properties and associated potential for tissue regeneration requires complex in vivo models comprising all steps of the angiogenic process. The highly vascularized extraembryonic chorioallantoic membrane (CAM) of fertilized chicken eggs offers a simple, easy accessible, and cheap angiogenic screening tool compared to other animal models. Although the CAM assay was initially primarily performed for evaluation of tumor growth and metastasis, stem cell studies using this model are increasing. In this review, a detailed summary of angiogenic observations of different mesenchymal, cardiac, and endothelial stem cell types and derivatives in the CAM model is presented. Moreover, we focus on the variation in experimental setup, including the benefits and limitations of in ovo and ex ovo protocols, diverse biological and synthetic scaffolds, imaging techniques, and outcome measures of neovascularization. Finally, advantages and disadvantages of the CAM assay as a model for angiogenesis in tissue engineering in comparison with alternative in vivo animal models are described. Impact statement The chorioallantoic membrane (CAM) assay is an easy and cheap screening tool for the angiogenic properties of stem cells and their associated potential in the tissue engineering field. This review offers an overview of all published angiogenic studies of stem cells using this model, with emphasis on the variation in used experimental timeline, culture protocol (in ovo vs. ex ovo), stem cell type (derivatives), scaffolds, and outcome measures of vascularization. The purpose of this overview is to aid tissue engineering researchers to determine the ideal CAM experimental setup based on their specific study goals.
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Affiliation(s)
- Greet Merckx
- Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium
| | - Hanna Tay
- Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Melissa Lo Monaco
- Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium.,Department of Veterinary Medicine, Faculty of Sciences, Integrated Veterinary Research Unit-Namur Research Institute for Life Science (IVRU-NARILIS), University of Namur, Namur, Belgium
| | - Marc van Zandvoort
- Department of Genetics and Cell Biology, School for Cardiovascular Diseases CARIM and School for Oncology and Development GROW, Maastricht University, Maastricht, the Netherlands
| | - Ward De Spiegelaere
- Department of Morphology, Faculty of Veterinary Medicine, Ghent University, Merelbeke, Belgium
| | - Ivo Lambrichts
- Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium
| | - Annelies Bronckaers
- Faculty of Medicine and Life Sciences, Biomedical Research Institute (BIOMED), Hasselt University, Diepenbeek, Belgium
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22
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Release of the Non-Steroidal Anti-Inflammatory Drug Flufenamic Acid by Multiparticulate Delivery Systems Promotes Adipogenic Differentiation of Adipose-Derived Stem Cells. MATERIALS 2020; 13:ma13071550. [PMID: 32230892 PMCID: PMC7178062 DOI: 10.3390/ma13071550] [Citation(s) in RCA: 4] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 01/22/2020] [Revised: 03/21/2020] [Accepted: 03/25/2020] [Indexed: 12/31/2022]
Abstract
Engineered tissue-like structures often instigate an inflammatory response in the host that can inhibit wound healing and ultimately lead to the rejection of the implant. In our previous study, we have characterized the properties and biocompatibility of novel multiparticulate drug delivery systems (MDDS), based on collagen matrix with gradual release of anti-inflammatory drug flufenamic acid, we evaluated their anti-inflammatory potential and demonstrated their efficiency against burns and soft tissue lesions. In addition to these results, FA was previously described as a stimulant for adipogenesis, therefore we hypothesized that MDDS might also be appropriate for adipose tissue engineering. After the cell-scaffold constructs were obtained, cell morphology, adhesion and spreading on the systems were highlighted by scanning electron microscopy, immunostaining and confocal microscopy. The effect of FA-enriched materials on adipogenesis was evaluated at gene and protein level, by RT-qPCR, confocal microscopy and immunohistochemistry. Our current work indicates that flufenamic acid plays a beneficial role in adipocyte differentiation, with a direct effect upon the gene and protein expression of important early and late markers of adipogenesis, such as PPARγ2 and perilipin.
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23
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Guan S, Zhang K, Li J. Recent Advances in Extracellular Matrix for Engineering Stem Cell Responses. Curr Med Chem 2019; 26:6321-6338. [DOI: 10.2174/0929867326666190704121309] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2018] [Revised: 12/02/2018] [Accepted: 01/25/2019] [Indexed: 02/06/2023]
Abstract
Stem cell transplantation is an advanced medical technology, which brings hope for the
treatment of some difficult diseases in the clinic. Attributed to its self-renewal and differential
ability, stem cell research has been pushed to the forefront of regenerative medicine and has become
a hot topic in tissue engineering. The surrounding extracellular matrix has physical functions
and important biological significance in regulating the life activities of cells, which may play crucial
roles for in situ inducing specific differentiation of stem cells. In this review, we discuss the
stem cells and their engineering application, and highlight the control of the fate of stem cells, we
offer our perspectives on the various challenges and opportunities facing the use of the components
of extracellular matrix for stem cell attachment, growth, proliferation, migration and differentiation.
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Affiliation(s)
- Shuaimeng Guan
- School of Life Science, Zhengzhou University, Zhengzhou 450000, China
| | - Kun Zhang
- School of Life Science, Zhengzhou University, Zhengzhou 450000, China
| | - Jingan Li
- School of Materials Science and Engineering, Zhengzhou University, Zhengzhou 450000, China
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24
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Stepwise Adipogenesis of Decellularized Cellular Extracellular Matrix Regulates Adipose Tissue-Derived Stem Cell Migration and Differentiation. Stem Cells Int 2019; 2019:1845926. [PMID: 31781233 PMCID: PMC6875313 DOI: 10.1155/2019/1845926] [Citation(s) in RCA: 23] [Impact Index Per Article: 3.8] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/04/2019] [Revised: 08/31/2019] [Accepted: 09/19/2019] [Indexed: 02/06/2023] Open
Abstract
Microenvironmental factors can modulate the cellular status of adipose tissue-derived stem cells (ASCs). In response to microenvironmental changes, cells can remodel extracellular matrix (ECM) proteins, which play an important role in regulating cell behaviors. During adipogenic differentiation, ECM components secreted from ASCs remodel dramatically. To evaluate the role of stepwise adipogenesis-induced cellular secretion of ECM on the behavior of ASCs, we cultured ASCs in growth and adipogenic media, and ECM secreted from cells was characterized and decellularized. The ASCs were then reseeded on decellularized ECM (d-ECM) to determine the regulatory effects of ECM on cellular behaviors. During adipogenesis, cell-secreted ECM underwent remodeling characterized by conversion from fibronectin-rich ECM to laminin-rich ECM. The cellular status of ASCs was tested after reseeding on decellularized ECM. When reseeded on growth d-ECM, ASCs exhibited greater migration ability. In contrast, ASCs seeded on adipogenic d-ECM underwent adipogenic differentiation. In addition, integrin subunit αv and integrins α6 and α7 were detected at significantly greater levels in ASCs cultured on growth and adipogenic d-ECM, respectively, suggesting that integrins play an important role in ASC migration and adipogenesis. This study demonstrated that stepwise adipogenesis-induced ECM production plays an important role in ASC migration and differentiation. In addition, this study provided a strategy to achieve precise regulation of stem cell function in adipose tissue engineering.
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25
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Naeem EM, Sajad D, Talaei-Khozani T, Khajeh S, Azarpira N, Alaei S, Tanideh N, Reza TM, Razban V. Decellularized liver transplant could be recellularized in rat partial hepatectomy model. J Biomed Mater Res A 2019; 107:2576-2588. [PMID: 31361939 DOI: 10.1002/jbm.a.36763] [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: 01/24/2019] [Revised: 07/12/2019] [Accepted: 07/22/2019] [Indexed: 12/28/2022]
Abstract
In situ recellularization of the liver decellularized scaffold is a potential therapeutic alternative for liver transplantation. We aimed to develop an in situ procedure for recellularization of the rat liver using sodium lauryl ether sulfate (SLES) compared with Triton X-100/SDS. Rat liver specimens were rinsed with PBS, decellularized with either Triton X-100/SDS or SLES, and finally rinsed by distilled water. The efficiency of decellularized liver scaffolds was evaluated by histological, confocal Raman microscopy, histochemical staining, and DNA quantification assessments. Finally, in vivo studies were done to assess the biocompatibility of the liver scaffold by serum biochemical parameters and the recellularization capacity by histological and immunohistochemistry staining. Findings confirmed the preservation of extracellular matrix (ECM) components such as reticular, collagen, glycosaminoglycans, and neutral carbohydrates in both Triton X-100/SDS- and SLES-treated livers. Hoechst, feulgen, Hematoxylin and eosin, and DNA quantification assessments confirmed complete genetic content removal. The serological parameters showed no adverse impact on the liver functions. Transplantation of SLES-treated cell-free decellularized liver showed extensive neovascularization along with migration of the fibrocytes and adipocytes and some immune cells. Also, immunohistochemical staining showed that the oval cells, stellate cells, cholangiocytes and hepatocytes invaded extensively into the graft. It is concluded that SLES can be considered as a promising alternative in the liver decellularization process, and the transplanted decellularized liver can appropriately be revascularized and regenerated.
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Affiliation(s)
- Erfani M Naeem
- Department of Basic Sciences, Histology Section, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Daneshi Sajad
- Department of Basic Sciences, Histology Section, Faculty of Veterinary Medicine, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Tahereh Talaei-Khozani
- Tissue Engineering Lab, Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran.,Laboratory for Stem Cell Research, Department of Anatomical Sciences, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sahar Khajeh
- Department of Biochemistry, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Negar Azarpira
- Transplant Research Center, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Sanaz Alaei
- Department of Reproductive Biology, School of Advanced Medical Sciences and Applied Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Nader Tanideh
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Pharmacology, School of Medicine, Shiraz University of Medical Sciences, Shiraz, Iran
| | - Tabandeh M Reza
- Department of Biochemistry and Molecular Biology, Shahid Chamran University of Ahvaz, Ahvaz, Iran
| | - Vahid Razban
- Stem Cells Technology Research Center, Shiraz University of Medical Sciences, Shiraz, Iran.,Department of Molecular Medicine, School of Advanced Medical Sciences and Technologies, Shiraz University of Medical Sciences, Shiraz, Iran
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26
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Basara G, Yue X, Zorlutuna P. Dual Crosslinked Gelatin Methacryloyl Hydrogels for Photolithography and 3D Printing. Gels 2019; 5:E34. [PMID: 31277240 PMCID: PMC6787727 DOI: 10.3390/gels5030034] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/09/2019] [Revised: 06/18/2019] [Accepted: 07/01/2019] [Indexed: 12/25/2022] Open
Abstract
Gelatin methacryloyl (GelMA) hydrogels have been used in tissue engineering and regenerative medicine because of their biocompatibility, photopatternability, printability, and tunable mechanical and rheological properties. However, low mechanical strength limits their applications in controlled drug release, non-viral gene therapy, and tissue and disease modeling. In this work, a dual crosslinking method for GelMA is introduced. First, photolithography was used to pattern the gels through the crosslinking of methacrylate incorporated amine groups of GelMA. Second, a microbial transglutaminase (mTGase) solution was introduced in order to enzymatically crosslink the photopatterned gels by initiating a chemical reaction between the glutamine and lysine groups of the GelMA hydrogel. The results showed that dual crosslinking improved the stiffness and rheological properties of the hydrogels without affecting cell viability, when compared to single crosslinking with either ultraviolet (UV) exposure or mTGase treatment. Our results also demonstrate that when treated with mTGase, hydrogels show decreased swelling properties and better preservation of photolithographically patterned shapes. Similar effects were observed when three dimensional (3D) printed and photocrosslinked substrates were treated with mTGase. Such dual crosslinking methods can be used to improve the mechanical properties and pattern fidelity of GelMA gels, as well as dynamic control of the stiffness of tissue engineered constructs.
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Affiliation(s)
- Gozde Basara
- Aerospace and Mechanical Engineering Department, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Xiaoshan Yue
- Aerospace and Mechanical Engineering Department, University of Notre Dame, Notre Dame, IN 46556, USA
| | - Pinar Zorlutuna
- Aerospace and Mechanical Engineering Department, University of Notre Dame, Notre Dame, IN 46556, USA.
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Khanmohammadi M, Golshahi H, Saffarian Z, Montazeri S, Khorasani S, Kazemnejad S. Repair of Osteochondral Defects in Rabbit Knee Using Menstrual Blood Stem Cells Encapsulated in Fibrin Glue: A Good Stem Cell Candidate for the Treatment of Osteochondral Defects. Tissue Eng Regen Med 2019; 16:311-324. [PMID: 31205859 DOI: 10.1007/s13770-019-00189-9] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/21/2018] [Revised: 02/26/2019] [Accepted: 03/18/2019] [Indexed: 02/07/2023] Open
Abstract
Background In recent years, researchers discovered that menstrual blood-derived stem cells (MenSCs) have the potential to differentiate into a wide range of tissues including the chondrogenic lineage. In this study, we aimed to investigate the effect of MenSCs encapsulated in fibrin glue (FG) on healing of osteochondral defect in rabbit model. Methods We examined the effectiveness of MenSCs encapsulated in FG in comparison with FG alone in the repair of osteochondral defect (OCD) lesions of rabbit knees after 12 and 24 weeks. Results Macroscopical evaluation revealed that the effectiveness of MenSCs incorporation with FG is much higher than FG alone in repair of OCD defects. Indeed, histopathological evaluation of FG + MenSCs group at 12 weeks post-transplantation demonstrated that defects were filled with hyaline cartilage-like tissue with proper integration, high content of glycosaminoglycan and the existence of collagen fibers especially collagen type II, as well as by passing time (24 weeks post-transplantation), the most regenerated tissue in FG + MenSCs group was similar to hyaline cartilage with relatively good infill and integration. As the same with the result of 12 weeks post-implantation, the total point of microscopical examination in FG + MenSCs group was higher than other experimental groups, however, no significant difference was detected between groups at 24 weeks (p > 0.05). Conclusion In summary, MenSCs as unique stem cell population, is suitable for in vivo repair of OCD defects and promising for the future clinical application.
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Affiliation(s)
- Manijeh Khanmohammadi
- 1Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, P.O. Box: 1177-19615 Tehran, Iran.,2Department of Obstetrics and Gynaecology, Monash University, Clayton, VIC Australia.,3The Ritchie Centre, Hudson Institute of Medical Research Clayton, VIC, Australia
| | - Hannaneh Golshahi
- 1Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, P.O. Box: 1177-19615 Tehran, Iran
| | - Zahra Saffarian
- 1Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, P.O. Box: 1177-19615 Tehran, Iran
| | - Samaneh Montazeri
- 1Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, P.O. Box: 1177-19615 Tehran, Iran
| | - Somaye Khorasani
- 1Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, P.O. Box: 1177-19615 Tehran, Iran
| | - Somaieh Kazemnejad
- 1Nanobiotechnology Research Center, Avicenna Research Institute, ACECR, P.O. Box: 1177-19615 Tehran, Iran
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28
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Effect of Collagen-Chitosan-Glycerol Composition in Scaffold for Gingival Recession Therapy. JOURNAL OF BIOMIMETICS BIOMATERIALS AND BIOMEDICAL ENGINEERING 2019. [DOI: 10.4028/www.scientific.net/jbbbe.40.101] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/02/2023]
Abstract
The case of gingival recession has a high prevalence, about 88% of the population of the United States in one or more locations suffering from gingival recession. One of the handling cases of gingival recession is to use scaffold that includes the development of tissue and cell engineering. This study aims to determine the best composition variation scaffold of collagen-chitosan with the addition of glycerol. The process of synthesis of collagen-chitosan-glycerol scaffold using freeze dry method that can form pores on the scaffold. Characterization was also carried out on the results of the synthesis of collagen-chitosan scaffold with the addition of glycerol include the morphological characterization, tensile, cytotoxicity, swelling, degradation, and thickness. The results of morphological characterization showed pore size ranged from 26.68 - 191.7 μm with a thickness of 0.51 - 0.65 mm which was suitable for handling of gingival recession cases. The result of tensile test showed that the variation of 9: 1 has the lowest value that is 2.87 MPa where the value is close to tensile strength value for periodontal which has a value ranging from 2.75 to 5.13. The characterization of cytotoxicity shows a value that is less in line with the literature, where live cells <50%. This is because collagen and chitosan have an acidic pH so that the cells cannot reproduce. Characterization of degradation shows all the variations experienced a severe reduction process from day to day. The characterization of the swelling of all samples was equilibrated at 7 minute. Chitosan-collagen scaffold with the addition of glycerol has good potential as a scaffold candidate for gingival recession therapy based on morphological characterization (thickness and surface structure), the mechanical strength (tensile strength), degradation, and the degree of swelling.
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29
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Bello AB, Park H, Lee SH. Current approaches in biomaterial-based hematopoietic stem cell niches. Acta Biomater 2018; 72:1-15. [PMID: 29578087 DOI: 10.1016/j.actbio.2018.03.028] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 09/26/2017] [Revised: 02/07/2018] [Accepted: 03/14/2018] [Indexed: 12/20/2022]
Abstract
Hematopoietic stem cells (HSCs) are multipotent progenitor cells that can differentiate and replenish blood and immune cells. While there is a growing demand for autologous and allogeneic HSC transplantation owing to the increasing incidence of hereditary and hematologic diseases, the low population of HSCs in cord-blood and bone marrow (the main source of HSCs) hinders their medical applicability. Several cytokine and growth factor-based methods have been developed to expand the HSCs in vitro; however, the expansion rate is low, or the expanded cells fail to survive upon engraftment. This is at least in part because the overly simplistic polystyrene culture substrates fail to fully replicate the microenvironments or niches where these stem cells live. Bone marrow niches are multi-dimensional, complex systems that involve both biochemical (cells, growth factors, and cytokines) and physiochemical (stiffness, O2 concentration, and extracellular matrix presentation) factors that regulate the quiescence, proliferation, activation, and differentiation of the HSCs. Although several studies have been conducted on in vitro HSC expansion via 2D and 3D biomaterial-based platforms, additional work is required to engineer an effective biomaterial platform that mimics bone marrow niches. In this study, the factors that regulate the HSC in vivo were explained and their applications in the engineering of a bone marrow biomaterial-based platform were discussed. In addition, current approaches, challenges, and the future direction of a biomaterial-based culture and expansion of the HSC were examined. STATEMENT OF SIGNIFICANCE Hematopoietic stem cells (HSC) are multipotent cells that can differentiate and replace the blood and immune cells of the body. However, in vivo, there is a low population of these cells, and thus their use in biotherapeutic and medical applications is limited (i.e., bone marrow transplantation). In this review, the biochemical factors (growth factors, cytokines, co-existing cells, ECM, gas concentrations, and differential gene expression) that may regulate the over-all fate of HSC, in vivo, were summarized and discussed. Moreover, different conventional and recent biomaterial platforms were reviewed, and their potential in generating a biomaterial-based, BM niche-mimicking platform for the efficient growth and expansion of clinically relevant HSCs in-vitro, was discussed.
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Affiliation(s)
- Alvin Bacero Bello
- School of Integrative Engineering, Chung-Ang University, Seoul 06911, Republic of Korea; Department of Biomedical Science, CHA University, Seongnam-Si 13488, Republic of Korea
| | - Hansoo Park
- School of Integrative Engineering, Chung-Ang University, Seoul 06911, Republic of Korea.
| | - Soo-Hong Lee
- Department of Biomedical Science, CHA University, Seongnam-Si 13488, Republic of Korea.
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30
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Prospects of Natural Polymeric Scaffolds in Peripheral Nerve Tissue-Regeneration. ADVANCES IN EXPERIMENTAL MEDICINE AND BIOLOGY 2018; 1077:501-525. [DOI: 10.1007/978-981-13-0947-2_27] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.6] [Reference Citation Analysis] [Track Full Text] [Subscribe] [Scholar Register] [Indexed: 02/06/2023]
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31
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Adipose Extracellular Matrix/Stromal Vascular Fraction Gel Secretes Angiogenic Factors and Enhances Skin Wound Healing in a Murine Model. BIOMED RESEARCH INTERNATIONAL 2017; 2017:3105780. [PMID: 28835892 PMCID: PMC5556995 DOI: 10.1155/2017/3105780] [Citation(s) in RCA: 39] [Impact Index Per Article: 4.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 04/29/2017] [Revised: 06/13/2017] [Accepted: 06/15/2017] [Indexed: 12/21/2022]
Abstract
Mesenchymal stem cells are an attractive cell type for cytotherapy in wound healing. The authors recently developed a novel, adipose-tissue-derived, injectable extracellular matrix/stromal vascular fraction gel (ECM/SVF-gel) for stem cell therapy. This study was designed to assess the therapeutic effects of ECM/SVF-gel on wound healing and potential mechanisms. ECM/SVF-gel was prepared for use in nude mouse excisional wound healing model. An SVF cell suspension and phosphate-buffered saline injection served as the control. The expression levels of vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), and monocyte chemotactic protein-1 (MCP-1) in ECM/SVF-gel were analyzed at different time points. Angiogenesis (tube formation) assays of ECM/SVF-gel extracts were evaluated, and vessels density in skin was determined. The ECM/SVF-gel extract promoted tube formation in vitro and increased the expression of the angiogenic factors VEGF and bFGF compared with those in the control. The expression of the inflammatory chemoattractant MCP-1 was high in ECM/SVF-gel at the early stage and decreased sharply during the late stage of wound healing. The potent angiogenic effects exerted by ECM/SVF-gel may contribute to the improvement of wound healing, and these effects could be related to the enhanced inflammatory response in ECM/SVF-gel during the early stage of wound healing.
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32
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Pan Y, Jiao G, Yang J, Guo R, Li J, Wang C. Insights into the Therapeutic Potential of Heparinized Collagen Scaffolds Loading Human Umbilical Cord Mesenchymal Stem Cells and Nerve Growth Factor for the Repair of Recurrent Laryngeal Nerve Injury. Tissue Eng Regen Med 2017; 14:317-326. [PMID: 30603488 PMCID: PMC6171598 DOI: 10.1007/s13770-017-0032-7] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 05/08/2016] [Revised: 07/05/2016] [Accepted: 08/22/2016] [Indexed: 12/16/2022] Open
Abstract
Recurrent laryngeal nerve (RLN) injury can result in unilateral or bilateral vocal cords paralysis, thereby causing a series of complications, such as hoarseness and dyspnea. However, the repair of RLN remains a great challenge in current medicine. This study aimed to develop human umbilical mesenchymal stem cells (HuMSCs) and nerve growth factor (NGF)-loaded heparinized collagen scaffolds (HuMSCs/NGF HC-scaffolds) and evaluate their potential in the repair of RLN injury. HuMSCs/NGF HC-scaffolds were prepared through incorporating HuMSCs and NGF into heparinized collagen scaffolds that were prefabricated by freeze-drying in a template. The resulting scaffolds were characterized by FTIR, SEM, porosity, degradation in vitro, NGF release in vitro and bioactivity. A rabbit RLN injury model was constructed to appraise the performance of HuMSCs/NGF HC-scaffolds for nerve injury repair. Electrophysiology, histomorphology and diagnostic proteins expression for treated nerves were checked after application of various scaffolds. The results showed that the composite scaffolds with HuMSCs and NGF were rather helpful for the repair of broken RLN. The RLN treated with HuMSCs/NGF HC-scaffolds for 8 weeks produced a relatively normal electromyogram, and the levels of calcium-binding protein S100, neurofilament and AchE pertinent to nerve were found to be close to the normal ones but higher than those resulted from other scaffolds. Taken together, HuMSCs/NGF HC-scaffolds exhibited a high score on the nerve injury repair and may be valuable for the remedy of RLN injury.
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Affiliation(s)
- Yongqin Pan
- Department of General Surgery, First Affiliated Hospital of Jinan University, No. 613 West Huangpu Avenue, Guangzhou, 510630 People’s Republic of China
| | - Genlong Jiao
- Department of Orthopedics, First Affiliated Hospital of Jinan University, Guangzhou, 510630 People’s Republic of China
| | - Jingge Yang
- Department of General Surgery, First Affiliated Hospital of Jinan University, No. 613 West Huangpu Avenue, Guangzhou, 510630 People’s Republic of China
| | - Rui Guo
- College of Life Science and Technology, Jinan University, Guangzhou, 510630 People’s Republic of China
| | - Jinyi Li
- Department of General Surgery, First Affiliated Hospital of Jinan University, No. 613 West Huangpu Avenue, Guangzhou, 510630 People’s Republic of China
| | - Cunchuan Wang
- Department of General Surgery, First Affiliated Hospital of Jinan University, No. 613 West Huangpu Avenue, Guangzhou, 510630 People’s Republic of China
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