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Regenerative Medicine Protocols: From Molecular Research to Application
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Regenerative Medicine Protocols: From Molecular Research to Application

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: closed (31 March 2023) | Viewed by 9423

Special Issue Editor

Dr. Marco Govoni

E-Mail Website
Guest Editor
Reconstructive Orthopaedic Surgery and Innovative Techniques—Musculoskeletal Tissue Bank, IRCCS Istituto Ortopedico Rizzoli, 40136 Bologna, Italy
Interests: tissue engineering and regenerative medicine; musculoskeletal system; multiscale technological devices; bioreactors
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Regenerative medicine has emerged as an important approach for the treatment of many clinical conditions dealing with functional restoration of specific damaged or injured tissues and/or organs. Considered a branch of translational research in tissue engineering and molecular biology, regenerative medicine includes the generation and use of therapeutic stem cells, as well as cell-based constructs, biomimetic scaffolds, allogeneic and xenogeneic tissues, bioactive molecules, and 3D static or dynamic cultures with appropriate biophysical cues.

Nevertheless, after more than thirty years of studies, it still remains a challenge to apply them to the clinical field, extending the regenerative approach to major diseases and conditions. Therefore, although recent scientific discoveries open up new approaches in the application of innovative regenerative medicine protocols, there is still much to be done, especially for overcoming regulatory and commercialization barriers.

In this Special Issue, we encourage authors to submit original articles and reviews focusing on the latest scientific findings on the most promising application of regenerative medicine protocols aimed at proposing directions for current and future therapies. The addressed topics include—but are not limited to—strategies for enhancing the intrinsic regenerative capacity of the host, methods for exploiting recently developed cell sources and cell-derivative carriers, 3D bioprinting, organoids, the use of combined products, growth factors, or biomechanical actuation systems.

Moreover, we welcome studies focused on innovative translational research to develop regenerative processes toward practical application.

Dr. Marco Govoni
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 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.

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

  • tissue engineering
  • regenerative medicine
  • 3D-cell-based constructs
  • 3D bioprinting
  • bioreactors
  • decellularization
  • allografts
  • xenografts
  • cell-derivative carriers
  • organoids
  • growth factors
  • translational research

Published Papers (4 papers)

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Research

18 pages, 3282 KiB  
Article
Characterization of Human Subcutaneous Adipose Tissue and Validation of the Banking Procedure for Autologous Transplantation
by Francesca Favaretto, Chiara Compagnin, Elisa Cogliati, Giulia Montagner, Francesco Dell’Antonia, Giorgio Berna, Roberto Vettor, Gabriella Milan and Diletta Trojan
Int. J. Mol. Sci. 2023, 24(9), 8190; https://doi.org/10.3390/ijms24098190 - 3 May 2023
Cited by 1 | Viewed by 1634
Abstract
Adipose tissue (AT) is composed of a heterogeneous population which comprises both progenitor and differentiated cells. This heterogeneity allows a variety of roles for the AT, including regenerative functions. In fact, autologous AT is commonly used to repair soft tissue defects, and its [...] Read more.
Adipose tissue (AT) is composed of a heterogeneous population which comprises both progenitor and differentiated cells. This heterogeneity allows a variety of roles for the AT, including regenerative functions. In fact, autologous AT is commonly used to repair soft tissue defects, and its cryopreservation could be a useful strategy to reduce the patient discomfort caused by multiple harvesting procedures. Our work aimed to characterize the cryopreserved AT and to validate its storage for up to three years for clinical applications. AT components (stromal vascular fraction-SVF and mature adipocytes) were isolated in fresh and cryopreserved samples using enzymatic digestion, and cell viability was assessed by immunofluorescence (IF) staining. Live, apoptotic and necrotic cells were quantified using cytometry by evaluating phosphatidylserine binding to fluorescent-labeled Annexin V. A multiparametric cytometry was also used to measure adipogenic (CD34+CD90+CD31−CD45−) and endothelial (CD34+CD31+CD45−) precursors and endothelial mature cells (CD34−CD31+CD45−). The maintenance of adipogenic abilities was evaluated using in vitro differentiation of SVF cultures and fluorescent lipid staining. We demonstrated that AT that is cryopreserved for up to three years maintains its differentiation potential and cellular composition. Given our results, a clinical study was started, and two patients had successful transplants without any complications using autologous cryopreserved AT. Full article
(This article belongs to the Special Issue Regenerative Medicine Protocols: From Molecular Research to Application)
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16 pages, 3507 KiB  
Article
Three-Dimensional Bioprinting of an In Vitro Lung Model
by Nádia Nascimento da Rosa, Julia Maurer Appel, Ana Carolina Irioda, Bassam Felipe Mogharbel, Nathalia Barth de Oliveira, Maiara Carolina Perussolo, Priscila Elias Ferreira Stricker, Lívia Rosa-Fernandes, Cláudio Romero Farias Marinho and Katherine Athayde Teixeira de Carvalho
Int. J. Mol. Sci. 2023, 24(6), 5852; https://doi.org/10.3390/ijms24065852 - 19 Mar 2023
Cited by 2 | Viewed by 2458
Abstract
In December 2019, COVID-19 emerged in China, and in January 2020, the World Health Organization declared a state of international emergency. Within this context, there is a significant search for new drugs to fight the disease and a need for in vitro models [...] Read more.
In December 2019, COVID-19 emerged in China, and in January 2020, the World Health Organization declared a state of international emergency. Within this context, there is a significant search for new drugs to fight the disease and a need for in vitro models for preclinical drug tests. This study aims to develop a 3D lung model. For the execution, Wharton’s jelly mesenchymal stem cells (WJ-MSC) were isolated and characterized through flow cytometry and trilineage differentiation. For pulmonary differentiation, the cells were seeded in plates coated with natural functional biopolymer matrix as membrane until spheroid formation, and then the spheroids were cultured with differentiation inductors. The differentiated cells were characterized using immunocytochemistry and RT-PCR, confirming the presence of alveolar type I and II, ciliated, and goblet cells. Then, 3D bioprinting was performed with a sodium alginate and gelatin bioink in an extrusion-based 3D printer. The 3D structure was analyzed, confirming cell viability with a live/dead assay and the expression of lung markers with immunocytochemistry. The results showed that the differentiation of WJ-MSC into lung cells was successful, as well as the bioprinting of these cells in a 3D structure, a promising alternative for in vitro drug testing. Full article
(This article belongs to the Special Issue Regenerative Medicine Protocols: From Molecular Research to Application)
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12 pages, 1070 KiB  
Article
Action of Platelet-Rich Plasma on In Vitro Cellular Bioactivity: More than Platelets
by Maider Beitia, Diego Delgado, Jon Mercader, Pello Sánchez, Leonor López de Dicastillo and Mikel Sánchez
Int. J. Mol. Sci. 2023, 24(6), 5367; https://doi.org/10.3390/ijms24065367 - 10 Mar 2023
Cited by 11 | Viewed by 1829
Abstract
Platelet-rich plasma (PRP) is a biological therapy in which one of the mechanisms of action is the stimulation of biological processes such as cell proliferation. The size of PRP’s effect depends on multiple factors, one of the most important being the composition of [...] Read more.
Platelet-rich plasma (PRP) is a biological therapy in which one of the mechanisms of action is the stimulation of biological processes such as cell proliferation. The size of PRP’s effect depends on multiple factors, one of the most important being the composition of PRP. The aim of this study was to analyze the relationship between cell proliferation and the levels of certain growth factors (IGF-1, HGF, PDGF, TGF-β and VEG) in PRP. First, the composition and effect on cell proliferation of PRP versus platelet-poor plasma (PPP) were compared. Subsequently, the correlation between each growth factor of PRP and cell proliferation was evaluated. Cell proliferation was higher in cells incubated with lysates derived from PRP compared to those cultured with lysates derived from PPP. In terms of composition, the levels of PDGF, TGF-β, and VEGF were significantly higher in PRP. When analyzing the PRP growth factors, IGF-1 was the only factor that correlated significantly with cell proliferation. Of those analyzed, the level of IGF-1 was the only one that did not correlate with platelet levels. The magnitude of PRP’s effect depends not only on platelet count but also on other platelet-independent molecules. Full article
(This article belongs to the Special Issue Regenerative Medicine Protocols: From Molecular Research to Application)
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13 pages, 2847 KiB  
Article
Bone Regeneration Guided by a Magnetized Scaffold in an Ovine Defect Model
by Melania Maglio, Maria Sartori, Alessandro Gambardella, Tatiana Shelyakova, Valentin Alek Dediu, Matteo Santin, Yolanda Piñeiro, Manuel Bañobre López, Josè Rivas, Anna Tampieri, Simone Sprio, Lucia Martini, Alessandro Gatti, Alessandro Russo, Gianluca Giavaresi and Milena Fini
Int. J. Mol. Sci. 2023, 24(1), 747; https://doi.org/10.3390/ijms24010747 - 1 Jan 2023
Cited by 4 | Viewed by 2763
Abstract
The reconstruction of large segmental defects still represents a critical issue in the orthopedic field. The use of functionalized scaffolds able to create a magnetic environment is a fascinating option to guide the onset of regenerative processes. In the present study, a porous [...] Read more.
The reconstruction of large segmental defects still represents a critical issue in the orthopedic field. The use of functionalized scaffolds able to create a magnetic environment is a fascinating option to guide the onset of regenerative processes. In the present study, a porous hydroxyapatite scaffold, incorporating superparamagnetic Fe3O4 nanoparticles (MNPs), was implanted in a critical bone defect realized in sheep metatarsus. Superparamagnetic nanoparticles functionalized with hyperbranched poly(epsilon-Lysine) peptides and physically complexed with vascular endothelial growth factor (VEGF) where injected in situ to penetrate the magnetic scaffold. The scaffold was fixed with cylindrical permanent NdFeB magnets implanted proximally, and the magnetic forces generated by the magnets enabled the capture of the injected nanoparticles forming a VEGF gradient in its porosity. After 16 weeks, histomorphometric measurements were performed to quantify bone growth and bone-to-implant contact, while the mechanical properties of regenerated bone via an atomic force microscopy (AFM) analysis were investigated. The results showed increased bone regeneration at the magnetized interface; this regeneration was higher in the VEGF-MNP-treated group, while the nanomechanical behavior of the tissue was similar to the pattern of the magnetic field distribution. This new approach provides insights into the ability of magnetic technologies to stimulate bone formation, improving bone/scaffold interaction. Full article
(This article belongs to the Special Issue Regenerative Medicine Protocols: From Molecular Research to Application)
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