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Advancements in Regenerative Medicine Research
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Advancements in Regenerative Medicine Research

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: 31 January 2027 | Viewed by 5145

Editor

Dr. Rosa V. Ventrella

E-Mail Website
Guest Editor
Precision Medicine Program, College of Graduate Studies, Midwestern University, Downers Grove, IL 60515, USA
Interests: regeneration; cell signaling; developmental biology; mechanotransduction; laser therapy; in vivo model systems

Special Issue Information

Dear Colleagues,

Regenerative medicine is a rapidly evolving and interdisciplinary field dedicated to the repair, replacement, or regeneration of human cells, tissues, and organs, to restore normal function. Grounded in stem cell biology, tissue engineering, and molecular signaling, this field holds transformative potential for the treatment of a wide range of conditions, including neurodegenerative disorders, musculoskeletal injuries, cardiovascular disease, diabetes, and organ failure. Despite growing interest and significant progress, many challenges remain, such as the limited integration of engineered tissues, immune rejection, safety concerns, and gaps in understanding the endogenous mechanisms of tissue repair.

This Special Issue aims to showcase recent breakthroughs and address ongoing challenges in regenerative medicine, with an emphasis on mechanistic discoveries, innovative technologies, and translational research that are advancing the field. By bringing together diverse scientific perspectives, this Special Issue aims to advance our understanding of regenerative processes, identify new therapeutic approaches, and foster the development of personalized, precision-based regenerative treatments.

Dr. Rosa V. Ventrella
Guest Editor

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

  • regenerative medicine
  • tissue repair
  • wound healing
  • stem cells
  • cell differentiation
  • cell signalling
  • gene regulation
  • mechanotransduction
  • precision medicine

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Published Papers (3 papers)

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Research

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28 pages, 5518 KB  
Article
Low-Frequency Electrical Stimulation Optimizes Neurotrophic and Neuroimmune Signaling in Bisvinyl Sulfonemethyl-Based Nerve Guidance Conduits
by Ching-Feng Su, Chung-Chia Chen, Wei-Cheng Hsu, Ming-Hsuan Lu, Joanna Pi-Jung Lee, Yung-Hsiang Chen and Yueh-Sheng Chen
Int. J. Mol. Sci. 2026, 27(9), 3820; https://doi.org/10.3390/ijms27093820 - 25 Apr 2026
Viewed by 597
Abstract
Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including [...] Read more.
Peripheral nerve injuries involving critical-sized gaps remain a major clinical challenge. Although autologous nerve grafting is considered the gold standard for peripheral nerve repair, its clinical application is limited by the availability of donor nerve tissue and the risk of donor-site morbidity, including sensory deficits and functional impairment. Therefore, nerve guidance conduits (NGCs) have emerged as a promising alternative when combined with bioactive modulation strategies. In this study, we evaluated bisvinyl sulfonemethyl (BVSM)-crosslinked gelatin conduits integrated with electrical stimulation (ES) at different frequencies (0, 2, 20, and 200 Hz) in a rat sciatic nerve defect model over a 4-week recovery period (n = 10 per group). Structural regeneration was assessed by morphometric analysis, electrophysiology, macrophage infiltration, CGRP immunoreactivity, retrograde Fluorogold tracing, quantitative PCR of growth factors and inflammatory cytokines, and behavioral testing. Among all stimulation paradigms, low-frequency ES at 2 Hz produced the most pronounced regenerative effects. The 2 Hz group demonstrated significantly greater axon number, axonal density, and regenerated nerve area compared with control and high-frequency groups (p < 0.05). Electrophysiological assessments revealed improved nerve conduction velocity, higher MAP amplitudes, and shorter latencies. Enhanced macrophage recruitment and elevated CGRP expression were observed, suggesting coordinated neuroimmune and neurochemical activation. Gene expression analysis indicated upregulation of neurotrophic factors and balanced inflammatory cytokine responses under low-frequency stimulation. In contrast, high-frequency stimulation (200 Hz) failed to enhance overall regeneration and showed reduced axonal metrics, suggesting possible overstimulation-associated suppression. Collectively, these findings demonstrate that BVSM-crosslinked conduits provide a stable and biocompatible regenerative scaffold, and that appropriately tuned low-frequency electrical stimulation (2 Hz) optimally enhances structural, molecular, and functional recovery. The integration of material engineering with bioelectrical modulation represents a promising strategy for next-generation bioelectronic interfaces in peripheral nerve repair. Full article
(This article belongs to the Special Issue Advancements in Regenerative Medicine Research)
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35 pages, 4696 KB  
Article
Neuronal Differentiation and Exosome Profiling of Dental Pulp Stem Cells: Unveiling Their Potential for Nerve Repair
by Bruna Lopes, Patrícia Sousa, Alícia de Sousa Moreira, Ana Catarina Sousa, Alexandra Rêma, Luís Atayde, António J. Salgado, Stefano Geuna, Rui Alvites and Ana Colette Maurício
Int. J. Mol. Sci. 2025, 26(19), 9723; https://doi.org/10.3390/ijms26199723 - 6 Oct 2025
Cited by 2 | Viewed by 2066
Abstract
Peripheral nerve injuries remain a major clinical problem, and cell-free therapies using stem cell-derived bioproducts have emerged as promising alternatives. This study evaluated the influence of neurogenic differentiation and passage number on the secretomic and exosomal profile of human dental pulp stem cells [...] Read more.
Peripheral nerve injuries remain a major clinical problem, and cell-free therapies using stem cell-derived bioproducts have emerged as promising alternatives. This study evaluated the influence of neurogenic differentiation and passage number on the secretomic and exosomal profile of human dental pulp stem cells (hDPCSs). Conditioned media from undifferentiated and neurodifferentiated hDPSCs, and exosomes derived from undifferentiated hDPSCs at passages 4 and 7, were analyzed using multiplex immunoassays, RT-PCR, and scanning electron microscopy (SEM). Neurodifferentiated hDPSCs at early passages secreted higher levels of neurotrophic, angiogenic and immunomodulatory factors, including FGF-2, IL-6, IL-8, and PDGF-AA. Exosomes from early-passage undifferentiated cells showed a more abundant and relevant neuroregenerative mRNA cargo in comparison to the later passages. Both cell types and exosomes adhered to the Reaxon® nerve guidance conduit, confirming the permissive nature of the materials regarding cells and cellular products, allowing adhesion and survival. Neurite outgrowth assays performed on neurodifferentiated hDPSCs confirmed functional neural behavior. In later passages, a decline in secretory and exosomal activity was noted. These results highlight the relevance of early-passage hDPSCs as a source of bioactive factors and support their application in cell-free approaches for peripheral nerve regeneration. Full article
(This article belongs to the Special Issue Advancements in Regenerative Medicine Research)
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Review

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23 pages, 2515 KB  
Review
Platelet-Rich Plasma from the Research to the Clinical Arena: A Journey Toward the Precision Regenerative Medicine
by Elisabetta Mormone, Vittoria D’Esposito, Paola De Luca, Fulvio E. O. Ferrara, Francesca P. Bellotti, Pietro Formisano and Eugenio Caradonna
Int. J. Mol. Sci. 2026, 27(2), 1058; https://doi.org/10.3390/ijms27021058 - 21 Jan 2026
Cited by 2 | Viewed by 1514
Abstract
Platelet-rich plasma (PRP) is a cornerstone of regenerative medicine, offering therapeutic potential across numerous clinical disciplines. Its efficacy relies on concentrated platelets and plasma components that release growth factors, cytokines, and extracellular vesicles to orchestrate tissue repair, immunomodulation, and angiogenesis. Recent findings have [...] Read more.
Platelet-rich plasma (PRP) is a cornerstone of regenerative medicine, offering therapeutic potential across numerous clinical disciplines. Its efficacy relies on concentrated platelets and plasma components that release growth factors, cytokines, and extracellular vesicles to orchestrate tissue repair, immunomodulation, and angiogenesis. Recent findings have uncovered novel mechanisms, such as mitochondrial transfer from platelets to target cells and the delivery of bioactive microRNAs that regulate inflammation and metabolic reprogramming. However, despite its potential, PRP therapy is often limited by inconsistent results. In this review, we examine how patient-specific factors—including age, comorbidities, and lifestyle—and technical variables in preparation and storage, influence the biological quality of the final product. Therefore, standardizing protocols and accounting for individual biological variability are essential for achieving reproducible outcomes. In conclusion, PRP is a complex therapeutic agent whose success depends on both intrinsic bioactive content and extrinsic processing factors. Integrating these molecular insights with personalized patient assessment is crucial to optimizing PRP treatment procedures. Future research should focus on refining standardization to fully establish PRP as a precision medicine tool in regenerative therapy. Full article
(This article belongs to the Special Issue Advancements in Regenerative Medicine Research)
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