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Regenerative Medicine: Biomaterials and Stem Cell Research

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Materials Science".

Deadline for manuscript submissions: 20 May 2025 | Viewed by 8937

Special Issue Editor


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Guest Editor
Grupo de Investigación en Terapia Celular y Medicina Regenerativa, Instituto de Investigación Biomédica de A Coruña (INIBIC), Complexo Hospitalario Universitario de A Coruña (CHUAC), Servizo Galego de Saúde (SERGAS), 15006 A Coruña, Spain
Interests: tissue engineering, regenerative medicine, cell therapy, bioprinting, stem cells
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Regenerative medicine is an emerging field that combines biomaterials and stem cells to repair, replace, or regenerate damaged tissues and organs. Biomaterials provide structural and biochemical support that facilitates tissue regeneration. They are designed to be biocompatible and, in many cases, biodegradable, allowing them to integrate safely into the body.

Stem cells, with their unique ability to differentiate into various types of specialized cells, are essential in this field. These cells can be obtained from various sources, such as embryonic, adult, and induced pluripotent stem cells (iPSCs). Research focuses on optimizing the conditions for the growth and differentiation of these cells in combination with suitable biomaterials.

This Special Issue wants to focus on both basic and clinical studies that incorporate biomolecular experiments to have a more complete comprehension on how the integration of biomaterials and stem cells in regenerative medicine is revolutionizing the ability to treat degenerative diseases, severe injuries, and the scarcity of organs for transplants, offering new hope for improving patients’ quality of life.

Dr. Silvia María Díaz-Prado
Guest Editor

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Keywords

  • regenerative medicine
  • stem cell
  • biomaterial
  • bioprinting
  • tissue engineering
  • tissue and organ transplant
  • organ scarcity

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Published Papers (4 papers)

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Research

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18 pages, 2875 KiB  
Article
Disease-Associated Signatures Persist in Extracellular Vesicles from Reprogrammed Cells of Osteoarthritis Patients
by María Piñeiro-Ramil, Iván Gómez-Seoane, Ana Isabel Rodríguez-Cendal, Clara Sanjurjo-Rodríguez, Selva Riva-Mendoza, Isaac Fuentes-Boquete, Javier De Toro-Santos, José Señarís-Rodríguez and Silvia Díaz-Prado
Int. J. Mol. Sci. 2025, 26(3), 870; https://doi.org/10.3390/ijms26030870 - 21 Jan 2025
Viewed by 864
Abstract
Osteoarthritis (OA) is a prevalent joint disorder that lacks effective therapies to halt cartilage degeneration. Mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs) are being investigated as promising chondroprotective agents. Compared to primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (MLCs) offer superior [...] Read more.
Osteoarthritis (OA) is a prevalent joint disorder that lacks effective therapies to halt cartilage degeneration. Mesenchymal stromal cell (MSC)-derived small extracellular vesicles (sEVs) are being investigated as promising chondroprotective agents. Compared to primary MSCs, induced pluripotent stem cell (iPSC)-derived MSCs (MLCs) offer superior scalability and enhanced paracrine activity. The aim of this study was to explore the feasibility of using autologous MLC-derived sEVs as a potential therapeutic strategy for OA through the analysis of their protein cargo. iPSCs from an OA patient and a healthy donor were differentiated into MLCs. sEVs were isolated from these MLCs and characterized, with a particular focus on their protein cargo. Both iPSC lines were successfully differentiated into MLCs, which secreted sEVs with comparable size distributions and yields. The analysis of differentially expressed proteins revealed a high abundance of proteins associated with OA pathology and cartilage degradation in sEVs from OA MLCs compared to those from healthy MLCs. The persistence of OA-associated protein signatures in autologous MLC-derived sEVs may limit their therapeutic efficacy. These findings underscore the importance of carefully evaluating disease-specific protein profiles in sEVs for regenerative applications. Full article
(This article belongs to the Special Issue Regenerative Medicine: Biomaterials and Stem Cell Research)
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18 pages, 31117 KiB  
Article
Synergistic Effects of Photobiomodulation and Differentiation Inducers on Osteogenic Differentiation of Adipose-Derived Stem Cells in Three-Dimensional Culture
by Daniella Da Silva, Anine Crous and Heidi Abrahamse
Int. J. Mol. Sci. 2024, 25(24), 13350; https://doi.org/10.3390/ijms252413350 (registering DOI) - 12 Dec 2024
Viewed by 1118
Abstract
Osteoporosis, a common metabolic bone disorder, leads to increased fracture risk and significant morbidity, particularly in postmenopausal women and the elderly. Traditional treatments often fail to fully restore bone health and may cause side effects, prompting the exploration of regenerative therapies. Adipose-derived stem [...] Read more.
Osteoporosis, a common metabolic bone disorder, leads to increased fracture risk and significant morbidity, particularly in postmenopausal women and the elderly. Traditional treatments often fail to fully restore bone health and may cause side effects, prompting the exploration of regenerative therapies. Adipose-derived stem cells (ADSCs) offer potential for osteoporosis treatment, but their natural inclination toward adipogenic rather than osteogenic differentiation poses a challenge. This study investigates a novel approach combining differentiation inducers (DIs), three-dimensional (3D) hydrogel scaffolds, and photobiomodulation (PBM) to promote osteogenic differentiation of immortalised ADSCs. A dextran-based 3D hydrogel matrix, supplemented with a DI cocktail of dexamethasone, β-glycerophosphate disodium, and ascorbic acid, was used to foster osteogenesis. PBM was applied using near-infrared (825 nm), green (525 nm), and combined wavelengths at fluences of 3 J/cm2, 5 J/cm2, and 7 J/cm2 to enhance osteogenic potential. Flow cytometry identified osteoblast-specific markers, while inverted light microscopy evaluated cellular morphology. Reactive oxygen species assays measured oxidative stress, and quantitative polymerase chain reaction (qPCR) revealed upregulated gene expression linked to osteogenesis. The findings demonstrate that integrating DIs, 3D hydrogels, and PBM effectively drives osteogenic differentiation in immortalised ADSCs. The PBM enhanced osteogenic marker expression, induced morphological changes, and upregulated gene activity, presenting a promising framework for bone regeneration. Future research should assess the stability and functionality of these differentiated cells and explore their applicability in preclinical models of bone injury or degeneration. This integrative approach demonstrated specific efficacy in promoting the osteogenic differentiation of ADSCs, highlighting its potential application in developing targeted treatments for osteoporosis. Full article
(This article belongs to the Special Issue Regenerative Medicine: Biomaterials and Stem Cell Research)
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14 pages, 2913 KiB  
Article
Morphometric, Biomechanical and Histologic Assessment of Physiologic Ovine Cervical Intervertebral Disc: An Experimental Study and Brief Literature Review
by Nikolaos Gkantsinikoudis, Savvas Koltsakidis, Panagiotis Prodromou, Eleni Aggelidou, Stylianos Kapetanakis, Eleftherios Tsiridis, Ioannis Magras, Dimitra Psalla, George Kazakos, Dimitrios Tzetzis and Aristeidis Kritis
Int. J. Mol. Sci. 2024, 25(23), 12579; https://doi.org/10.3390/ijms252312579 - 22 Nov 2024
Viewed by 806
Abstract
The ovine cervical spine model has been established as a representative model of the human cervical spine in the current literature, and is the most commonly used large animal model in studies investigating pathogenesis and treatment strategies for intervertebral disc (IVD) degeneration. However, [...] Read more.
The ovine cervical spine model has been established as a representative model of the human cervical spine in the current literature, and is the most commonly used large animal model in studies investigating pathogenesis and treatment strategies for intervertebral disc (IVD) degeneration. However, existing data regarding morphometry, biomechanical profiles and the microscopic features of a physiological ovine cervical IVD remain scarce. Hence, the aim of this study was to perform a multimodal morphometric, biomechanical and histologic evaluation of a normal ovine cervical IVD. For this purpose, nine ovine cervical IVDs were harvested from three female sheep, and subjected to morphometrical, biomechanical and histologic analyses. The biomechanical assessment included the performance of cyclic compression, creepand compressive strength tests in a controlledlaboratory environment. Histological evaluation was performed using hematoxylin–eosin, Masson’s trichrome and Alcian blue staining. The results from the morphometric analysis showed that the range of disc heights was 4–9 mm in all surfaces, featuring a constant increase from cranial to caudal levels. Biomechanical evaluation revealed that cyclic loading for 20 cycles was necessary for preconditioning so that the repeatability of the force–displacement hysteresis response is present. The critical failure point was defined at 15.5 MPa, whereas Young’s modulus of elasticity was 1.2 MPa. The histologic assessment demonstrated the presence of a concentric arrangement of collagen lamellae in external annulus fibrosus, along with the sparsely organized internal nucleus pulposus. Ovine cervical IVD represents a complex structure with distinct features that should be considered by researchers in this field in order to optimize the reliability and validity of testing results. Full article
(This article belongs to the Special Issue Regenerative Medicine: Biomaterials and Stem Cell Research)
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Review

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29 pages, 1560 KiB  
Review
The Future of Bone Repair: Emerging Technologies and Biomaterials in Bone Regeneration
by Julia Weronika Łuczak, Małgorzata Palusińska, Damian Matak, Damian Pietrzak, Paweł Nakielski, Sławomir Lewicki, Marta Grodzik and Łukasz Szymański
Int. J. Mol. Sci. 2024, 25(23), 12766; https://doi.org/10.3390/ijms252312766 - 27 Nov 2024
Cited by 5 | Viewed by 5373
Abstract
Bone defects and fractures present significant clinical challenges, particularly in orthopedic and maxillofacial applications. While minor bone defects may be capable of healing naturally, those of a critical size necessitate intervention through the use of implants or grafts. The utilization of traditional methodologies, [...] Read more.
Bone defects and fractures present significant clinical challenges, particularly in orthopedic and maxillofacial applications. While minor bone defects may be capable of healing naturally, those of a critical size necessitate intervention through the use of implants or grafts. The utilization of traditional methodologies, encompassing autografts and allografts, is constrained by several factors. These include the potential for donor site morbidity, the restricted availability of suitable donors, and the possibility of immune rejection. This has prompted extensive research in the field of bone tissue engineering to develop advanced synthetic and bio-derived materials that can support bone regeneration. The optimal bone substitute must achieve a balance between biocompatibility, bioresorbability, osteoconductivity, and osteoinductivity while simultaneously providing mechanical support during the healing process. Recent innovations include the utilization of three-dimensional printing, nanotechnology, and bioactive coatings to create scaffolds that mimic the structure of natural bone and enhance cell proliferation and differentiation. Notwithstanding the advancements above, challenges remain in optimizing the controlled release of growth factors and adapting materials to various clinical contexts. This review provides a comprehensive overview of the current advancements in bone substitute materials, focusing on their biological mechanisms, design considerations, and clinical applications. It explores the role of emerging technologies, such as additive manufacturing and stem cell-based therapies, in advancing the field. Future research highlights the need for multidisciplinary collaboration and rigorous testing to develop advanced bone graft substitutes, improving outcomes and quality of life for patients with complex defects. Full article
(This article belongs to the Special Issue Regenerative Medicine: Biomaterials and Stem Cell Research)
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