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Medicina
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Biomaterials for Reconstructive and Regenerative Medicine: From Research to Translational...
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Biomaterials for Reconstructive and Regenerative Medicine: From Research to Translational Applications

A special issue of Medicina (ISSN 1648-9144). This special issue belongs to the section "Translational Medicine".

Deadline for manuscript submissions: closed (25 July 2022) | Viewed by 25711

Special Issue Editors

Dr. Francesco De Francesco

E-Mail Website
Guest Editor
Department of Reconstructive Surgery and Hand Surgery, Azienda Ospedaliera Universitaria delle Marche, 60126 Ancona, Italy
Interests: adipose stem cells; regenerative medicine; smart biomaterials; osteoarthritis; novel technologies; exosomes
Special Issues, Collections and Topics in MDPI journals
Dr. Veronica Romano

E-Mail Website
Co-Guest Editor
Department of Public Health, University of Naples Federico II, 80131 Naples, Italy
Interests: cardiac tissue engineering; extracellular matrix; biomaterials; three-dimensional cell cultures; stem cells; gene expression profiling
Special Issues, Collections and Topics in MDPI journals
Dr. Arman Saparov

E-Mail Website
Co-Guest Editor
Department of Medicine, School of Medicine, Nazarbayev University, Nur-Sultan, Kazakhstan
Interests: immunology; inflammation; cardiovascular disease; stem cells; biomaterials; tissue engineering

Special Issue Information

Dear Colleagues,

The field of tissue engineering is advancing rapidly, and many of these advances would not have been possible without the innovative design and development of biomaterials. The intent of this Special Issue is to cover recent advances and emerging evolvements in the design and development of biomaterials for engineering a wide range of tissues. More recently, biomaterials that can be used as enabling medical platforms in combination with biofabrication technologies have emerged as a powerful paradigm for the next generation of medicine. Research on biomaterials for tissue engineering and regenerative medicine covers various interdisciplinary aspects. Depending on the final application, scaffolds and drug release materials have to fulfill a number of very different, sometimes even contradictory requirements.

The Special Issue will consider the main types of biomaterials, synthetic and natural, which are being investigated for tissue engineering applications, including biodegradable polymers, hydrogels, polypeptides, inorganic materials such as bioactive ceramics and glasses, and composites, as well as technologies for forming these biomaterials into tissue engineering constructs with nanofibrous, microfibrous, and macroporous three-dimensional architectures. Biomaterials for stem-cell-based therapies and for growth factors and drug delivery are also of interest. In this Special Issue, we are inviting submissions exploring the latest advances in basic and applied research in the field of biomaterials and fabrication (e.g., cell and tissue engineering scaffolds, decellularized extracellular matrix, wearable medical sensors, micro-and nanomedicine, 3D bioprinting, biologically inspired engineering, organ chips, bioelectronics, etc.). We are pleased to invite you to contribute original articles and reviews, as well as survey articles specifying recent efforts in biomaterials used in stem cell-based therapies, including natural polymers and related hybrids, their synthesis as well as structural analysis, in vitro and in vivo cell culture and signal transduction studies, and preclinical and clinical trials.

Dr. Francesco De Francesco
Dr. Veronica Romano
Dr. Arman Saparov
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. Medicina is an international peer-reviewed open access monthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). 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

  • biomaterials
  • biofabrication
  • regenerative and reconstructive medicine
  • tissue engineering
  • cell-based therapies
  • growth factors
  • drug delivery
  • engineered scaffolds
  • extracellular matrix

Published Papers (5 papers)

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Research

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10 pages, 3358 KiB  
Article
Comparison of Efficacy among Three Dermal Substitutes in the Management of Critical Lower-Limb Wounds: The Largest Biases-Reduced Single-Center Retrospective Cohort Study in Literature
by Giuseppe Cottone, Francesco Amendola, Carlo Strada, Maria Chiara Bagnato, Roberto Brambilla, Francesco De Francesco and Luca Vaienti
Medicina 2021, 57(12), 1367; https://doi.org/10.3390/medicina57121367 - 15 Dec 2021
Cited by 8 | Viewed by 2636
Abstract
Background and objectives: The skin recently became the main focus of regenerative medicine and, in this context, skin substitutes are fully entering into the plastic surgeon’s armamentarium. Among the various types of skin substitutes, dermal substitutes (DSs) are the most used. Our [...] Read more.
Background and objectives: The skin recently became the main focus of regenerative medicine and, in this context, skin substitutes are fully entering into the plastic surgeon’s armamentarium. Among the various types of skin substitutes, dermal substitutes (DSs) are the most used. Our study aims to retrospectively compare three renowned and extremely similar DS in the management of critical lower limb wounds in the largest cohort analysis currently present in literature. Materials and Methods: We followed a strict protocol of application and evaluation of the DS for each patient and wound and, after a meticulous bias reduction process, we compared final outcomes in terms of efficacy and speed in achieving the defect coverage. Results: Among patients who did not receive a skin graft after the DS, we registered a wound healed surface of 50% for Pelnac, 52% for Integra, and 19% for Nevelia, after 30 days from the external silicon layer removal; among those who received a skin graft after the DS, we observed a significantly lower mean percentage of graft take after 7 days with Pelnac (53%) compared to Integra and Nevelia (92% and 80%, respectively). The overall percentage of wound healed surface obtained after 30 days from the external silicon sheet removal, either with or without skin graft, was 71% for Pelnac, 63% for Integra and 63% for Nevelia. We also ran a sub-group analysis only including grafted wounds with a negative microbiological test and the mean percentage of graft take was similar this time. Eventually, we assessed the influence of the wound’s “chronicity” on its healing, comparing the mean graft take only in “acute” wounds who received a skin graft and it resulted 63% for Pelnac, 91% for Integra and 75% for Nevelia. Conclusions: Integra demonstrates the highest rate of skin graft viability and the highest rate of skin graft takes after 7 days. Pelnac shows the quickest induction of secondary healing in acute wounds. Nevelia is not different from Integra and shows a superior graft take compared to Pelnac, but features the lowest secondary healing induction rate. No differences exist between the three DSs in terms of wound healing after 30 days from the skin graft or from the removal of the external silicon layer. Full article
(This article belongs to the Special Issue Biomaterials for Reconstructive and Regenerative Medicine: From Research to Translational Applications)
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14 pages, 2262 KiB  
Article
Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma or Hyaluronic Acid for the Treatment of Knee Osteoarthritis
by Oliver Dulic, Predrag Rasovic, Ivica Lalic, Vaso Kecojevic, Gordan Gavrilovic, Dzihan Abazovic, Dusan Maric, Mladen Miskulin and Marko Bumbasirevic
Medicina 2021, 57(11), 1193; https://doi.org/10.3390/medicina57111193 - 02 Nov 2021
Cited by 25 | Viewed by 8233
Abstract
Background: In the last decade, regenerative therapies have become one of the leading disease modifying options for treatment of knee osteoarthritis (OA). Still, there is a lack of trials with a direct comparison of different biological treatments. Our aim was to directly compare [...] Read more.
Background: In the last decade, regenerative therapies have become one of the leading disease modifying options for treatment of knee osteoarthritis (OA). Still, there is a lack of trials with a direct comparison of different biological treatments. Our aim was to directly compare clinical outcomes of knee injections of Bone Marrow Aspirate Concentrate (BMAC), Platelet-rich Plasma (PRP), or Hyaluronic acid (HA) in the OA treatment. Methods: Patients with knee pain and osteoarthritis KL grade II to IV were randomized to receive a BMAC, PRP, and HA injection in the knee. VAS, WOMAC, KOOS, and IKDC scores were used to establish baseline values at 1, 3, 6, 9, and 12 months. All side effects were reported. Results: A total of 175 patients with a knee osteoarthritis KL grade II-IV were randomized; 111 were treated with BMAC injection, 30 with HA injection, and 34 patients with PRP injection. There were no differences between these groups when considering KL grade, BMI, age, or gender. There were no serious side effects. The mean VAS scores after 3, 7, 14, and 21 days showed significant differences between groups with a drop of VAS in all groups but with a difference in the BMAC group in comparison to other groups (p < 0.001). There were high statistically significant differences between baseline scores and those after 12 months (p < 0.001) in WOMAC, KOOS, KOOS pain, and IKDC scores, and in addition, there were differences between these scores in the BMAC group in comparison with other groups, except for the PRP group in WOMAC and the partial IKDC score. There were no differences between the HA and PRP groups, although PRP showed a higher level of clinical improvement. Conclusions: Bone marrow aspirate concentrate, Leukocyte rich Platelet Rich Plasma, and Hyaluronic acid injections are safe therapeutic options for knee OA and provide positive clinical outcomes after 12 months in comparison with findings preceding the intervention. BMAC could be better in terms of clinical improvements in the treatment of knee OA than PRP and HA up to 12 months. PRP provides better outcomes than HA during the observation period, but these results are not statistically significant. More randomized controlled trials and high quality comparative studies are needed for direct correlative conclusions. Full article
(This article belongs to the Special Issue Biomaterials for Reconstructive and Regenerative Medicine: From Research to Translational Applications)
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Review

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26 pages, 1215 KiB  
Review
Peptide-Based Drug Delivery Systems
by Dmitriy Berillo, Adilkhan Yeskendir, Zharylkasyn Zharkinbekov, Kamila Raziyeva and Arman Saparov
Medicina 2021, 57(11), 1209; https://doi.org/10.3390/medicina57111209 - 05 Nov 2021
Cited by 35 | Viewed by 9688
Abstract
Peptide-based drug delivery systems have many advantages when compared to synthetic systems in that they have better biocompatibility, biochemical and biophysical properties, lack of toxicity, controlled molecular weight via solid phase synthesis and purification. Lysosomes, solid lipid nanoparticles, dendrimers, polymeric micelles can be [...] Read more.
Peptide-based drug delivery systems have many advantages when compared to synthetic systems in that they have better biocompatibility, biochemical and biophysical properties, lack of toxicity, controlled molecular weight via solid phase synthesis and purification. Lysosomes, solid lipid nanoparticles, dendrimers, polymeric micelles can be applied by intravenous administration, however they are of artificial nature and thus may induce side effects and possess lack of ability to penetrate the blood-brain barrier. An analysis of nontoxic drug delivery systems and an establishment of prospective trends in the development of drug delivery systems was needed. This review paper summarizes data, mainly from the past 5 years, devoted to the use of peptide-based carriers for delivery of various toxic drugs, mostly anticancer or drugs with limiting bioavailability. Peptide-based drug delivery platforms are utilized as peptide–drug conjugates, injectable biodegradable particles and depots for delivering small molecule pharmaceutical substances (500 Da) and therapeutic proteins. Controlled drug delivery systems that can effectively deliver anticancer and peptide-based drugs leading to accelerated recovery without significant side effects are discussed. Moreover, cell penetrating peptides and their molecular mechanisms as targeting peptides, as well as stimuli responsive (enzyme-responsive and pH-responsive) peptides and peptide-based self-assembly scaffolds are also reviewed. Full article
(This article belongs to the Special Issue Biomaterials for Reconstructive and Regenerative Medicine: From Research to Translational Applications)
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Other

Jump to: Research, Review

18 pages, 612 KiB  
Systematic Review
Efficacy of Adipose-Derived Mesenchymal Stem Cells and Stromal Vascular Fraction Alone and Combined to Biomaterials in Tendinopathy or Tendon Injury: Systematic Review of Current Concepts
by Letizia Senesi, Francesco De Francesco, Andrea Marchesini, Pier Paolo Pangrazi, Maddalena Bertolini, Valentina Riccio and Michele Riccio
Medicina 2023, 59(2), 273; https://doi.org/10.3390/medicina59020273 - 31 Jan 2023
Cited by 4 | Viewed by 2174
Abstract
Background and Objectives: Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic global burden. Despite the current treatments available, either surgical or conservative, the tendon healing process is [...] Read more.
Background and Objectives: Tendon injury and tendinopathy are among the most frequent musculoskeletal diseases and represent a challenging issue for surgeons as well as a great socio-economic global burden. Despite the current treatments available, either surgical or conservative, the tendon healing process is often suboptimal and impaired. This is due to the inherent scarce ability of tendon tissue to repair and return itself to the original structure. Recently, Adipose-derived mesenchymal stem cells (ADSC) and stromal vascular fraction (SVF) have gained a central interest in the scientific community, demonstrating their effectiveness in treatments of acute and chronic tendon disorders in animals and humans. Either enzymatic or mechanical procedures to obtain ADSC and SVF have been described and used in current clinical practice. However, no unified protocols and processes have been established. Materials and Methods: This systematic review aims at providing a comprehensive update of the literature on the clinical application of ADSC enzymatically or mechanically processed to obtain SVF, alone and in association with biomaterials in the local treatment of tendinopathy and tendon injury in vivo, in animal models and humans. The study was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA). Results: Thirty-two articles met our inclusion criteria, with a total of 18 studies in animals, 10 studies in humans and 4 studies concerning the application of biomaterials in vivo in animals. The review of the literature suggests that ADSC/SVF therapy can represent a promising alternative in tendonregenerative medicine for the enhancement of tendon healing. Conclusions: Nevertheless, further investigations and randomized control trials are needed to improve the knowledge, standardize the procedures and extend the consensus on their use for such applications. Full article
(This article belongs to the Special Issue Biomaterials for Reconstructive and Regenerative Medicine: From Research to Translational Applications)
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11 pages, 3382 KiB  
Case Report
A Histological Evaluation of Artificial Dermal Scaffold Used in Micrograft Treatment: A Case Study of Micrograft and NPWT Performed on a Postoperative Ulcer Formation after Tumor Resection
by Yuta Niimi, Kyoko Baba, Masako Tsuchida and Akira Takeda
Medicina 2022, 58(1), 73; https://doi.org/10.3390/medicina58010073 - 04 Jan 2022
Cited by 5 | Viewed by 1948
Abstract
Background and Objectives: Wound healing (WH) is a complex natural process: the achieving of a proper WH with standard therapies sometimes is not fulfilled and it is often observed in aged and diabetic patients, leading to intractable ulcers. In recent years, autologous [...] Read more.
Background and Objectives: Wound healing (WH) is a complex natural process: the achieving of a proper WH with standard therapies sometimes is not fulfilled and it is often observed in aged and diabetic patients, leading to intractable ulcers. In recent years, autologous micrograft (AMG) therapies have become a new, effective, and affordable wound care strategy among both researchers and clinicians. In this study, a 72-year-old female patient underwent a combination of treatments using micrograft and negative pressure wound therapy (NPWT) on a postoperative skin ulcer after a benign tumor resection on the back with the aim to present an innovative method to treat skin ulceration using AMG combined with an artificial dermal scaffold and NPWT. Materials and Methods: A section of the artificial dermal scaffold, infused with micrografts, was sampled prior to transplant, and sections were collected postoperatively on days 3 and 7. Hematoxylin-eosin (HE) and immunohistochemical stains were employed for the evaluation of Cytokeratin AE1/AE3, desmin, and Factor VIII. Additionally, on postoperative day 3, NPWT dressing was evaluated using HE stains, as well. The resulting HE and immunostaining analysis revealed red blood cells and tissue fragments within the collagen layers of the artificial dermis prior to transplant. On postoperative day 3, collagen layers of the artificial dermis revealed red blood cells and neutrophils based on HE stains, and scattering of cytokeratin AE1/AE3-positive cells were detected by immunostaining. The HE stains on postoperative day 7 showed more red blood cells and neutrophils within the collagen layers of the artificial dermis than on day 3, an increase in cytokeratin AE1/AE3-positive cells, and tissue stained positively with desmin and Factor VIII. Results: Results suggest that the effects of both micrografts and migratory cells have likely accelerated the wound healing process. Furthermore, the NPWT dressing on day 3 showed almost no cells within the dressing. This indicated that restarting NPWT therapy immediately after micrograft transplant did not draw out cells within the scaffold. Conclusions: Micrograft treatment and NPWT may serve to be a useful combination therapy for complex processes of wound healing. Full article
(This article belongs to the Special Issue Biomaterials for Reconstructive and Regenerative Medicine: From Research to Translational Applications)
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