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Advanced Research on Regenerative Medicine
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Advanced Research on Regenerative Medicine

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 June 2025 | Viewed by 9226

Special Issue Editors

Dr. Alberto Ruffilli

E-Mail Website
Guest Editor
IRCCS Rizzoli Orthopedic Institute, 40125 Bologna, Italy
Interests: regenerative medicine; orthopedic surgery
Prof. Dr. Cesare Faldini

E-Mail Website
Guest Editor
1. Department of Biomedical and Neuromotor Science (DIBINEM), University of Bologna, 40125 Bologna, Italy
2. 1st Orthopaedic and Traumatologic Clinic, IRCCS Rizzoli Orthopaedic Institute, 40125 Bologna, Italy
Interests: orthopaedic surgery; spine; hip; knee; foot and ankle; paediatric orthopaedics
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Regenerative medicine represents an important resource to address a large number of diseases. This field has seen significant growth in recent years, with its applications varying widely among different specialties.

At present, the three major strategies being explored in the field of regenerative medicine include: replacing damaged tissues by transplanting cell suspensions or aggregates; implanting bioartificial tissues or organs produced in laboratories that can replace natural tissues; Regeneration induction is performed on the damaged tissue part. However, none of the strategies has yielded completely satisfactory results so far.

An accurate, high-quality collection of scientific papers on this topic is sadly still missing. Moreover, it is necessary to explore all aspects of the subject in order to better understand its current state and the potential for future development.

Suitable topics include but are not limited to cell-based therapies in all fields of medicine and regenerative strategies for orthopedic, spinal, and neurosurgical diseases.  

Dr. Alberto Ruffilli
Prof. Dr. Cesare Faldini
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 100 words) can be sent to the Editorial Office for announcement on this website.

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.

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Published Papers (4 papers)

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Research

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19 pages, 8676 KiB  
Article
Comparison of Muscle Regeneration Effects at Different Melittin Concentrations in Rabbit Atrophied Muscle
by Byeong-Churl Jang, Eun Sang Kwon, Yoon-Jin Lee, Jae Ik Jung, Yong Suk Moon and Dong Rak Kwon
Int. J. Mol. Sci. 2024, 25(9), 5035; https://doi.org/10.3390/ijms25095035 - 5 May 2024
Viewed by 1419
Abstract
This research aimed to explore the healing impacts of Melittin treatment on gastrocnemius muscle wasting caused by immobilization with a cast in rabbits. Twenty-four rabbits were randomly allocated to four groups. The procedures included different injections: 0.2 mL of normal saline to Group [...] Read more.
This research aimed to explore the healing impacts of Melittin treatment on gastrocnemius muscle wasting caused by immobilization with a cast in rabbits. Twenty-four rabbits were randomly allocated to four groups. The procedures included different injections: 0.2 mL of normal saline to Group 1 (G1-NS); 4 μg/kg of Melittin to Group 2 (G2-4 μg/kg Melittin); 20 μg/kg of Melittin to Group 3 (G3-20 μg/kg Melittin); and 100 μg/kg of Melittin to Group 4 (G4-100 μg/kg Melittin). Ultrasound was used to guide the injections into the rabbits’ atrophied calf muscles following two weeks of immobilization via casting. Clinical measurements, including the length of the calf, the compound muscle action potential (CMAP) of the tibial nerve, and the gastrocnemius muscle thickness, were assessed. Additionally, cross-sectional slices of gastrocnemius muscle fibers were examined, and immunohistochemistry and Western blot analyses were performed following two weeks of therapy. The mean regenerative changes, as indicated by clinical parameters, in Group 4 were significantly more pronounced than in the other groups (p < 0.05). Furthermore, the cross-sectional area of the gastrocnemius muscle fibers and immunohistochemical indicators in Group 4 exceeded those in the remaining groups (p < 0.05). Western blot analysis also showed a more significant presence of anti-inflammatory and angiogenic cytokines in Group 4 compared to the others (p < 0.05). Melittin therapy at a higher dosage can more efficiently activate regeneration in atrophied gastrocnemius muscle compared to lower doses of Melittin or normal saline. Full article
(This article belongs to the Special Issue Advanced Research on Regenerative Medicine)
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16 pages, 2914 KiB  
Article
Pulsed Electromagnetic Fields Induce Skeletal Muscle Cell Repair by Sustaining the Expression of Proteins Involved in the Response to Cellular Damage and Oxidative Stress
by Silvia Maiullari, Antonella Cicirelli, Angela Picerno, Francesca Giannuzzi, Loreto Gesualdo, Angela Notarnicola, Fabio Sallustio and Biagio Moretti
Int. J. Mol. Sci. 2023, 24(23), 16631; https://doi.org/10.3390/ijms242316631 - 23 Nov 2023
Cited by 5 | Viewed by 2987
Abstract
Pulsed electromagnetic fields (PEMF) are employed as a non-invasive medicinal therapy, especially in the orthopedic field to stimulate bone regeneration. However, the effect of PEMF on skeletal muscle cells (SkMC) has been understudied. Here, we studied the potentiality of 1.5 mT PEMF to [...] Read more.
Pulsed electromagnetic fields (PEMF) are employed as a non-invasive medicinal therapy, especially in the orthopedic field to stimulate bone regeneration. However, the effect of PEMF on skeletal muscle cells (SkMC) has been understudied. Here, we studied the potentiality of 1.5 mT PEMF to stimulate early regeneration of human SkMC. We showed that human SkMC stimulated with 1.5 mT PEMF for four hours repeated for two days can stimulate cell proliferation without inducing cell apoptosis or significant impairment of the metabolic activity. Interestingly, when we simulated physical damage of the muscle tissue by a scratch, we found that the same PEMF treatment can speed up the regenerative process, inducing a more complete cell migration to close the scratch and wound healing. Moreover, we investigated the molecular pattern induced by PEMF among 26 stress-related cell proteins. We found that the expression of 10 proteins increased after two consecutive days of PEMF stimulation for 4 h, and most of them were involved in response processes to oxidative stress. Among these proteins, we found that heat shock protein 70 (HSP70), which can promote muscle recovery, inhibits apoptosis and decreases inflammation in skeletal muscle, together with thioredoxin, paraoxonase, and superoxide dismutase (SOD2), which can also promote skeletal muscle regeneration following injury. Altogether, these data support the possibility of using PEMF to increase SkMC regeneration and, for the first time, suggest a possible molecular mechanism, which consists of sustaining the expression of antioxidant enzymes to control the important inflammatory and oxidative process occurring following muscle damage. Full article
(This article belongs to the Special Issue Advanced Research on Regenerative Medicine)
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15 pages, 2283 KiB  
Article
Polydeoxyribonucleotide and Shock Wave Therapy Sequence Efficacy in Regenerating Immobilized Rabbit Calf Muscles
by Yoon-Jin Lee, Yong Suk Moon, Dong Rak Kwon, Sung Cheol Cho and Eun Ho Kim
Int. J. Mol. Sci. 2023, 24(16), 12820; https://doi.org/10.3390/ijms241612820 - 15 Aug 2023
Cited by 1 | Viewed by 2043
Abstract
This study primarily aimed to investigate the combined effects of polydeoxyribonucleotide (PDRN) and extracorporeal shock wave therapy (ESWT) sequences on the regenerative processes in atrophied animal muscles. Thirty male New Zealand rabbits, aged 12 weeks, were divided into five groups: normal saline (Group [...] Read more.
This study primarily aimed to investigate the combined effects of polydeoxyribonucleotide (PDRN) and extracorporeal shock wave therapy (ESWT) sequences on the regenerative processes in atrophied animal muscles. Thirty male New Zealand rabbits, aged 12 weeks, were divided into five groups: normal saline (Group 1), PDRN (Group 2), ESWT (Group 3), PDRN injection before ESWT (Group 4), and PDRN injection after ESWT (Group 5). After 2 weeks of cast immobilization, the respective treatments were administered to the atrophied calf muscles. Radial ESWT was performed twice weekly. Calf circumference, tibial nerve compound muscle action potential (CMAP), and gastrocnemius (GCM) muscle thickness after 2 weeks of treatment were evaluated. Histological and immunohistochemical staining, as well as Western blot analysis, were conducted 2 weeks post-treatment. Staining intensity and extent were assessed using semi-quantitative scores. Groups 4 and 5 demonstrated significantly greater calf muscle circumference, GCM muscle thickness, tibial nerve CMAP, and GCM muscle fiber cross-sectional area (type I, type II, and total) than the remaining three groups (p < 0.05), while they did not differ significantly in these parameters. Groups 2 and 3 showed higher values for all the mentioned parameters than Group 1 (p < 0.05). Group 4 had the greatest ratio of vascular endothelial growth factor (VEGF) to platelet endothelial cell adhesion molecule-1 (PECAM-1) in the GCM muscle fibers compared to the other four groups (p < 0.05). Western blot analysis revealed significantly higher expression of angiogenesis cytokines in Groups 4 and 5 than in the other groups (p < 0.05). The combination of ESWT and PDRN injection demonstrated superior regenerative efficacy for atrophied calf muscle tissue in rabbit models compared to these techniques alone or saline. In particular, administering ESWT after PDRN injection yielded the most favorable outcomes in specific parameters. Full article
(This article belongs to the Special Issue Advanced Research on Regenerative Medicine)
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Review

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13 pages, 2656 KiB  
Review
Osteobiologies for Spinal Fusion from Biological Mechanisms to Clinical Applications: A Narrative Review
by Byeong-Rak Keum, Hong Jin Kim, Gun-Hwa Kim and Dong-Gune Chang
Int. J. Mol. Sci. 2023, 24(24), 17365; https://doi.org/10.3390/ijms242417365 - 11 Dec 2023
Cited by 1 | Viewed by 1814
Abstract
Degenerative lumbar spinal disease (DLSD), including spondylolisthesis and spinal stenosis, is increasing due to the aging population. Along with the disease severity, lumbar interbody fusion (LIF) is a mainstay of surgical treatment through decompression, the restoration of intervertebral heights, and the stabilization of [...] Read more.
Degenerative lumbar spinal disease (DLSD), including spondylolisthesis and spinal stenosis, is increasing due to the aging population. Along with the disease severity, lumbar interbody fusion (LIF) is a mainstay of surgical treatment through decompression, the restoration of intervertebral heights, and the stabilization of motion segments. Currently, pseudoarthrosis after LIF is an important and unsolved issue, which is closely related to osteobiologies. Of the many signaling pathways, the bone morphogenetic protein (BMP) signaling pathway contributes to osteoblast differentiation, which is generally regulated by SMAD proteins as common in the TGF-β superfamily. BMP-2 and -4 are also inter-connected with Wnt/β-catenin, Notch, and FGF signaling pathways. With the potent potential for osteoinduction in BMP-2 and -4, the combination of allogenous bone and recombinant human BMPs (rhBMPs) is currently an ideal fusion material, which has equalized or improved fusion rates compared to traditional materials. However, safety issues in the dosage of BMP remain, so overcoming current limitations will provide significant advancement in spine surgery. In the future, translational research and the application of clinical study will be important to overcome the current limitations of spinal surgery. Full article
(This article belongs to the Special Issue Advanced Research on Regenerative Medicine)
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