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Regenerative Medicine: Molecular Mechanisms Driving Tissue Regeneration and Repair
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Regenerative Medicine: Molecular Mechanisms Driving Tissue Regeneration and Repair

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

Deadline for manuscript submissions: 20 June 2026 | Viewed by 8508

Special Issue Editors

Dr. Christopher Robinson

E-Mail Website
Guest Editor
Department of Anesthesiology, Perioperative, and Pain Medicine, Harvard Medical School, Boston, MA 02115, USA
Interests: regenerative medicine; growth factors; gene therapy; exosomes; extracellular vesicles; proteomics; genomics; CRISPR; stem cells
Special Issues, Collections and Topics in MDPI journals
Dr. Paul Jordan Christo

E-Mail Website
Guest Editor
Division of Pain Medicine, Department of Anesthesiology and Critical Care Medicine, The Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA
Interests: regenerative medicine; gene therapy; stem cells; platelet-rich plasma
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

The restoration of damaged or diseased tissues through regenerative medicine holds significant potential across a wide range of clinical applications. While major strides have been made in cell-based therapies, biomaterials, and tissue engineering, a detailed understanding of the molecular mechanisms that orchestrate tissue regeneration and repair remains critical to advancing safe and effective therapies. This Special Issue of the International Journal of Molecular Sciences invites original research articles and reviews focused on elucidating the molecular and cellular pathways that underline regenerative processes in mammalian systems. Topics of interest include but are not limited to the following: stem cells and signaling, immune modulation in repair, extracellular matrix remodeling, mechanotransduction, epigenetic reprogramming, and the role of growth factors, gene regulation, gene editing, or extracellular vesicles in regeneration.

By bringing together high-impact research at the interface of molecular biology and regenerative medicine, this Special Issue aims to foster deeper mechanistic insights that will inform next-generation therapeutic strategies for tissue restoration and functional recovery.

Dr. Christopher Robinson
Dr. Paul Jordan Christo
Guest Editors

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 250 words) can be sent to the Editorial Office for assessment.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • stem cell
  • cell signaling
  • immune modulation
  • extracellular matrix
  • remodeling
  • gene regulation
  • gene editing
  • growth factors
  • extracellular vesicles
  • small molecules

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Published Papers (3 papers)

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19 pages, 4098 KB  
Article
Effect of Human Amniotic Membrane with Aligned Electrospun Nanofiber Transplantation on Tendon Regeneration in Rats
by Mohamed Nasheed, Mohd Yazid Bajuri, Jia Xian Law and Nor Amirrah Ibrahim
Int. J. Mol. Sci. 2026, 27(2), 650; https://doi.org/10.3390/ijms27020650 - 8 Jan 2026
Viewed by 585
Abstract
Tendon injuries, whether resulting from trauma, repetitive strain, or degenerative conditions, present a considerable clinical challenge. The natural healing process, which involves inflammatory, proliferative, and remodeling phases, is often inefficient and leads to excessive scar tissue formation, ultimately compromising the mechanical properties of [...] Read more.
Tendon injuries, whether resulting from trauma, repetitive strain, or degenerative conditions, present a considerable clinical challenge. The natural healing process, which involves inflammatory, proliferative, and remodeling phases, is often inefficient and leads to excessive scar tissue formation, ultimately compromising the mechanical properties of the tendon compared to its native state. This highlights the critical need for innovative approaches to enhance tendon repair and regeneration. Leveraging the regenerative properties of human amniotic membrane (HAM) and electrospun PCL/gelatin nanofibers, this study aims to develop and assess a novel composite scaffold in a rodent model to facilitate improved tendon healing. This prospective experimental study involved 12 male Sprague Dawley rats (250–300 g), randomly assigned to three groups: Group A (No Treatment/No HAM), Group B (HAM-treated), and Group C (HAM with electrospun nanofibers, HAM-NF). A surgically induced tendon injury was created in the left hind limb, while the right limb served as a control. Following surgery, HAM and HAM-NF (0.5 cm2) were applied to the respective treatment groups, and tendon healing was assessed after six weeks. Gait analysis, including stride length and toe-out angle, was conducted both pre-operatively and six weeks post-operatively. Macroscopic and microscopic evaluations were performed on harvested tendons to assess regeneration, comparing treated groups to the controls. Gait analysis demonstrated that the HAM-NF group showed a significant increase in stride length from 11.70 ± 1.50 cm to 12.79 ± 1.71 cm (p < 0.05), with only a modest change in toe-out angle (14.58 ± 2.96° to 16.27 ± 2.20°). In contrast, the No Treatment group exhibited reduced stride length (10.27 ± 2.17 cm to 8.40 ± 1.67 cm) and a marked increase in toe-out angle (16.33 ± 4.51° to 26.47 ± 5.81°, p < 0.05), while the HAM-only group showed mild changes in both parameters. Macroscopic evaluation showed a significant difference in tendon healing. HAM-NF group had the highest score that indicates more rapid tissue regeneration. Histological analysis after 6 weeks showed that tendons treated with HAM-NF achieved a mean histological score of 5.54 ± 4.14, closely resembling the uninjured tendon (6.67 ± 1.63), indicating substantial regenerative potential. The combination of human amniotic membrane (HAM) and electrospun nanofibers presents significant potential as an effective strategy for tendon regeneration. The HAM/NF group exhibited consistent improvements in gait parameters and histological outcomes, closely mirroring those of uninjured tendons. These preliminary results indicate that this biomaterial-based approach can enhance both functional recovery and structural integrity, providing a promising pathway for advanced tendon repair therapies. Full article
(This article belongs to the Special Issue Regenerative Medicine: Molecular Mechanisms Driving Tissue Regeneration and Repair)
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Review

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17 pages, 746 KB  
Review
New Concepts of Regeneration and Renewal of Adrenal Chromaffin Cells
by Nataliya V. Yaglova, Sergey S. Obernikhin, Svetlana V. Nazimova, Valentin V. Yaglov, Ekaterina P. Timokhina, Elina S. Tsomartova, Marina Y. Ivanova, Elizaveta V. Chereshneva, Tatiana A. Lomanovskaya and Dibakhan A. Tsomartova
Int. J. Mol. Sci. 2025, 26(19), 9369; https://doi.org/10.3390/ijms26199369 - 25 Sep 2025
Viewed by 2380
Abstract
Chromaffin cells are neuroendocrine cells found in the adrenal medulla and paraganglia. They represent enigmatic cell population with origins and properties that have undergone a change in scientific interpretations over the last few decades. Earlier concepts consider that chromaffin cells derive from neuronal [...] Read more.
Chromaffin cells are neuroendocrine cells found in the adrenal medulla and paraganglia. They represent enigmatic cell population with origins and properties that have undergone a change in scientific interpretations over the last few decades. Earlier concepts consider that chromaffin cells derive from neuronal progenitors, and their cell fate is similar to neurons that lack the ability to proliferate and maintain renewal of cell population in postnatal life. Growing evidence of postnatal proliferation and response to proliferative stimuli were inconsistent with traditional views and required their reassessment and further research on chromaffin cell regeneration sources. The present review summarizes data on embryonic origin and development and transcriptional control of the adrenal chromaffin cells as well as available information about their postnatal proliferation. The authors also represent their findings in cellular and molecular events associated with the physiological transition from organ growth to self-maintenance of cell populations in intact rats and in experimental dismorphogenesis of the adrenals. The authors familiarize readers with available information about the early development and molecular changes in chromaffin cells in postnatal period and propose their new theories concerning mechanisms of adrenomedullary chromaffin cell regeneration. Further research on induction and management of these mechanisms will allow us to maintain cultured chromaffin cells in vitro, which will obviously make a significant contribution to practical regenerative medicine. Full article
(This article belongs to the Special Issue Regenerative Medicine: Molecular Mechanisms Driving Tissue Regeneration and Repair)
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21 pages, 1744 KB  
Review
Fibroblast–Myofibroblast Transition in Osteoarthritis Progression: Current Insights
by Ruixin Peng, Qiyuan Lin, Zhen Yang, Hui Li, Jiao Jiao Li and Dan Xing
Int. J. Mol. Sci. 2025, 26(16), 7881; https://doi.org/10.3390/ijms26167881 - 15 Aug 2025
Cited by 6 | Viewed by 4022
Abstract
Osteoarthritis (OA) is a multifactorial joint disease traditionally characterized by cartilage degradation, while growing evidence underscores the critical role of synovial fibrosis in driving disease progression. The synovium exhibits pathological remodeling in OA, primarily due to the phenotypic transition of fibroblast-like synoviocytes (FLSs) [...] Read more.
Osteoarthritis (OA) is a multifactorial joint disease traditionally characterized by cartilage degradation, while growing evidence underscores the critical role of synovial fibrosis in driving disease progression. The synovium exhibits pathological remodeling in OA, primarily due to the phenotypic transition of fibroblast-like synoviocytes (FLSs) into myofibroblasts. This fibroblast–myofibroblast transition (FMT) results in excessive deposition of extracellular matrix (ECM) and increased tissue stiffness and contractility, collectively contributing to chronic inflammation and fibrotic stiffening of the joint capsule. These fibrotic changes not only impair synovial function but also exacerbate cartilage degeneration, nociceptive sensitization, and joint dysfunction, thereby amplifying OA severity. Focusing on the frequently overlooked role of the FMT of synovial fibroblasts in OA, this review introduces the biological characteristics of FLSs and myofibroblasts and systematically examines the key molecular pathways implicated in OA-related FMT, including TGF-β, Wnt/β-catenin, YAP/TAZ, and inflammatory signaling cascades. It also discusses emerging therapeutic strategies targeting synovial fibrosis and FMT and considers their implications for the clinical management of OA. By highlighting recent advances and unresolved challenges, this review provides critical insights into the fibroblast–myofibroblast axis as a central contributor to OA progression and a promising therapeutic target for modifying disease trajectory. Full article
(This article belongs to the Special Issue Regenerative Medicine: Molecular Mechanisms Driving Tissue Regeneration and Repair)
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