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Bio-Organic Materials for Tissue Engineering and Regenerative Medicine

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A special issue of Pharmaceutics (ISSN 1999-4923). This special issue belongs to the section "Nanomedicine and Nanotechnology".

Deadline for manuscript submissions: closed (20 January 2023) | Viewed by 15433

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Special Issue Editors

Dr. Cornel Balta

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Guest Editor

“Aurel Ardelean” Institute of Life Sciences, Vasile Goldis Western University of Arad, 86 Revolutiei, 310025 Arad, Romania
Interests: tissue engineering; regenerative medicine; bio-organic materials; bone regeneration; antifibrotic effect; bio-organic materials evaluations; biocompatibility; biocompatibility assessment methods; biomarkers used in therapeutic evaluation
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Prof. Dr. Anca Oana Hermenean

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Co-Guest Editor

Faculty of Medicine, Department of Histology, Vasile Goldis Western University of Arad, Arad, Romania
Interests: histochemistry; immunohistochemistry; microscopy; cell biology; antioxidant activity; phytomedicine; regenerative medicine
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Dr. Oana-Maria Boldura

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Co-Guest Editor

Faculty of Veterinary Medicine, University of Agricultural Sciences and Veterinary Medicine “King Michael I” of Banat Timişoara, Calea Aradului 119, 300645 Timişoara, Romania
Interests: molecular signalling; inflammation pathways; apoptosis pathways; phytotherapy
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Special Issue Information

Dear Colleagues,

Tissue engineering is an area of expanding research that is directly interconnected with physics, biochemistry, and molecular biology, with the goal of obtaining new materials, devices, or methods for use in current therapeutic practice. Regenerative medicine is trying to find and develop new therapeutic methods and compounds that can lead to the recovery of affected or lost organic function. The combination of these two areas of research presents a perfect fusion of engineering with medicine, promoting and bringing about new therapeutic materials and strategies used in the partial or total recovery of altered organic functions.

The main objective of this Special Issue is to gather top specialists in the field of tissue engineering and regenerative medicine, who will share in this volume the latest and current research in the field in order to contribute decisively to the progress of this branch of medicine, which is of particular interest from the application point of view, bringing real curative benefits by bringing new knowledge that will lead to the improvement of current medical therapies.

This volume aims to bring together high-quality scientific papers developed by researchers and leading specialists in the following fields: tissue engineering and regenerative medicine at the bone level, tissue engineering used to obtain aesthetic protests after amputation operations, tissue engineering used for obtaining various editorial grafts, regenerative medicine and bioactive compounds used in the recovery of various functions of the body, such as hepatic, renal, cardiac, reproductive, or endocrine, as well as models and experimental techniques used in tissue engineering. The scientific materials obtained, materialized in scientific papers of real value, will be published in this Special Issue in the prestigious international journal Pharmaceutics.

For the current Special Issue, original research and review articles addressing bio-organic materials for tissue engineering and regenerative medicine are welcomed.

Dr. Cornel Balta
Prof. Dr. Anca Oana Hermenean
Dr. Oana-Maria Boldura
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. Pharmaceutics 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 2900 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

tissue engineering
regenerative medicine
bio-organic materials
bone regeneration
biocompatibility
biocompatibility assessment methods
biomarkers used in therapeutic evaluation

Published Papers (9 papers)

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Research

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14 pages, 1546 KiB

Open AccessArticle

Release Kinetics of Monomers from Dental Composites Containing Fluoride-Doped Calcium Phosphates

by Adrián M. Alambiaga-Caravaca, Alicia López-Castellano, Yu Fu Chou, Arlinda Luzi, Juan Manuel Núñez, Avijit Banerjee, María del Mar Jovani Sancho and Salvatore Sauro

Pharmaceutics 2023, 15(7), 1948; https://doi.org/10.3390/pharmaceutics15071948 - 14 Jul 2023

Cited by 2 | Viewed by 1128

Abstract

This study analyse the type of release kinetic of specific monomers from dental resin composites containing various fluoride-doped calcium phosphates. The release behavior of urethane dimethacrylate (UDMA), ethoxylated bisphenol-A dimethacrylate (bis-EMA) and 1.6-hexanediol ethoxylate diacrylate (HEDA) was evaluated over a period of 35 days. Two tailored calcium phosphates doped with different concentrations of fluoride salts (VS10% and VS20%) were prepared and incorporated in the dimethacrylate matrix at various concentrations to generate a range of experimental composites. The release kinetics were characterized using mathematical models such as zero-order, first-order, Peppas and Higuchi models. The results showed that the first-order model best described the release kinetics. UDMA and HEDA exhibited significant differences in release compared to bis-EMA from day 1, while no significant differences were observed between UDMA and HEDA, except on day 35, when UDMA exhibited a higher release rate than HEDA. When comparing the release of each monomer, VS20-R20% had the highest total release percentage, with 3.10 ± 0.25%, whereas the composite VS10-R5% showed the lowest release percentage, with a total of 1.66 ± 0.08%. The release kinetics were influenced by the composition of the resin composites and the presence of calcium fluoride and sodium fluoride in the calcium phosphate played a role in the maximum amounts of monomer released. In conclusion, the release of monomers from the tested resin composites followed a first-order kinetic behaviour, with an initial rapid release that decreased over time. The composition of the resin monomers and the presence of fluoride salts influenced the release kinetics. The VS10-R5% and VS10-R10% resin composites exhibited the lowest total monomer release, suggesting its potential favourable composition with reduced monomer elution. These findings contribute to understanding the release behavior of dental resin composites and provide insights for the development of resin-based bioactive dental materials. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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15 pages, 5677 KiB

Open AccessArticle

Electrosprayed Mesenchymal Stromal Cell Extracellular Matrix Nanoparticles Accelerate Cellular Wound Healing and Reduce Gram-Negative Bacterial Growth

by Emily N. Wandling, Keera Rhoads, Dennis E. Ohman and Rebecca L. Heise

Pharmaceutics 2023, 15(4), 1277; https://doi.org/10.3390/pharmaceutics15041277 - 19 Apr 2023

Cited by 1 | Viewed by 1145

Abstract

Treatments for acute respiratory distress syndrome are still unavailable, and the prevalence of the disease has only increased due to the COVID-19 pandemic. Mechanical ventilation regimens are still utilized to support declining lung function but also contribute to lung damage and increase the risk for bacterial infection. The anti-inflammatory and pro-regenerative abilities of mesenchymal stromal cells (MSCs) have shown to be a promising therapy for ARDS. We propose to utilize the regenerative effects of MSCs and the extracellular matrix (ECM) in a nanoparticle. Our mouse MSC (MMSC) ECM nanoparticles were characterized using size, zeta potential, and mass spectrometry to evaluate their potential as pro-regenerative and antimicrobial treatments. The nanoparticles had an average size of 273.4 nm (±25.6) and possessed a negative zeta potential, allowing them to surpass defenses and reach the distal regions of the lung. It was found that the MMSC ECM nanoparticles are biocompatible with mouse lung epithelial cells and MMSCs, increasing the wound healing rate of human lung fibroblasts while also inhibiting the growth of Pseudomonas aeruginosa, a common lung pathogen. Our MMSC ECM nanoparticles display characteristics of healing injured lungs while preventing bacterial infection, which can increase recovery time. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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16 pages, 4477 KiB

Open AccessArticle

Functionalization of 3D-Printed Titanium Scaffolds with Elastin-like Recombinamers to Improve Cell Colonization and Osteoinduction

by Jordi Guillem-Marti, Elia Vidal, Alessandra Girotti, Aina Heras-Parets, Diego Torres, Francisco Javier Arias, Maria-Pau Ginebra, Jose Carlos Rodriguez-Cabello and Jose Maria Manero

Pharmaceutics 2023, 15(3), 872; https://doi.org/10.3390/pharmaceutics15030872 - 08 Mar 2023

Cited by 4 | Viewed by 1574

Abstract

The 3D printing of titanium (Ti) offers countless possibilities for the development of personalized implants with suitable mechanical properties for different medical applications. However, the poor bioactivity of Ti is still a challenge that needs to be addressed to promote scaffold osseointegration. The aim of the present study was to functionalize Ti scaffolds with genetically modified elastin-like recombinamers (ELRs), synthetic polymeric proteins containing the elastin epitopes responsible for their mechanical properties and for promoting mesenchymal stem cell (MSC) recruitment, proliferation, and differentiation to ultimately increase scaffold osseointegration. To this end, ELRs containing specific cell-adhesive (RGD) and/or osteoinductive (SN_A15) moieties were covalently attached to Ti scaffolds. Cell adhesion, proliferation, and colonization were enhanced on those scaffolds functionalized with RGD-ELR, while differentiation was promoted on those with SN_A15-ELR. The combination of both RGD and SN_A15 into the same ELR stimulated cell adhesion, proliferation, and differentiation, although at lower levels than those for every single moiety. These results suggest that biofunctionalization with SN_A15-ELRs could modulate the cellular response to improve the osseointegration of Ti implants. Further investigation on the amount and distribution of RGD and SN_A15 moieties in ELRs could improve cell adhesion, proliferation, and differentiation compared to the present study. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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21 pages, 16631 KiB

Open AccessArticle

H₂O₂-PLA-(Alg)₂Ca Hydrogel Enriched in Matrigel^® Promotes Diabetic Wound Healing

by Alexandra Cătălina Bîrcă, Cristina Chircov, Adelina Gabriela Niculescu, Herman Hildegard, Cornel Baltă, Marcel Roșu, Bianca Mladin, Oana Gherasim, Dan Eduard Mihaiescu, Bogdan Ștefan Vasile, Alexandru Mihai Grumezescu, Ecaterina Andronescu and Anca Oana Hermenean

Pharmaceutics 2023, 15(3), 857; https://doi.org/10.3390/pharmaceutics15030857 - 06 Mar 2023

Cited by 6 | Viewed by 1941

Abstract

Hydrogel-based dressings exhibit suitable features for successful wound healing, including flexibility, high water-vapor permeability and moisture retention, and exudate absorption capacity. Moreover, enriching the hydrogel matrix with additional therapeutic components has the potential to generate synergistic results. Thus, the present study centered on diabetic wound healing using a Matrigel-enriched alginate hydrogel embedded with polylactic acid (PLA) microspheres containing hydrogen peroxide (H₂O₂). The synthesis and physicochemical characterization of the samples, performed to evidence their compositional and microstructural features, swelling, and oxygen-entrapping capacity, were reported. For investigating the three-fold goal of the designed dressings (i.e., releasing oxygen at the wound site and maintaining a moist environment for faster healing, ensuring the absorption of a significant amount of exudate, and providing biocompatibility), in vivo biological tests on wounds of diabetic mice were approached. Evaluating multiple aspects during the healing process, the obtained composite material proved its efficiency for wound dressing applications by accelerating wound healing and promoting angiogenesis in diabetic skin injuries. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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17 pages, 2398 KiB

Open AccessArticle

Immunomodulatory Effect of Novel Electrospun Nanofibers Loaded with Doxycycline as an Adjuvant Treatment in Periodontitis

by Vlad Andrei, Sanda Andrei, Adrian Florin Gal, Vasile Rus, Luciana-Mădălina Gherman, Bianca Adina Boșca, Mihaela Niculae, Reka Barabas, Oana Cadar, Elena Dinte, Dana-Maria Muntean, Cosmin Petru Peștean, Horațiu Rotar, Antonia Boca, Andreea Chiș, Manuela Tăut, Sebastian Candrea and Aranka Ilea

Pharmaceutics 2023, 15(2), 707; https://doi.org/10.3390/pharmaceutics15020707 - 20 Feb 2023

Cited by 6 | Viewed by 1994

Abstract

The immunomodulatory effect of a novel biomaterial obtained through electrospinning, based on polylactic acid (PLA) and nano-hydroxyapatite (nano-HAP), loaded with doxycycline (doxy) was evaluated in an animal model. The treatment capabilities as a local non-surgical treatment of periodontitis was investigated on the lower incisors of Wistar rats, after the induction of localized periodontitis using the ligature technique. Following the induction of the disease, the non-surgical treatment of scaling and root planing was applied, in conjunction with the application of the new material. The results of the treatment were evaluated clinically, using the tooth mobility and gingival index scores, as well as histologically. The salivary concentrations of matrix metalloproteinase 8 (MMP-8) and plasmatic concentrations of interleukin 1 (IL-1), interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-α) were also monitored. Two weeks after the ligature application, the periodontal disease was successfully induced in rats. The application of the novel biomaterial obtained through electrospinning was proven to be more effective in improving the clinical parameters, while decreasing the salivary MMP-8 and plasmatic IL-1 and TNF-α concentrations, compared to the simple scaling and root planing. Thus, the novel electrospun biomaterial could be a strong candidate as an adjuvant to the non-surgical periodontal therapy. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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12 pages, 3785 KiB

Open AccessArticle

Irisin Role in Chondrocyte 3D Culture Differentiation and Its Possible Applications

by Francesca Posa, Roberta Zerlotin, Anastasia Ariano, Michele Di Cosola, Graziana Colaianni, Aldo Di Fazio, Silvia Colucci, Maria Grano and Giorgio Mori

Pharmaceutics 2023, 15(2), 585; https://doi.org/10.3390/pharmaceutics15020585 - 09 Feb 2023

Cited by 3 | Viewed by 1389

Abstract

Irisin is a recently discovered cytokine, better known as an exercise-induced myokine, produced primarily in skeletal muscle tissue as a response to exercise. Although the skeleton was initially identified as the main target of Irisin, its action is also proving effective in many other tissues. Physical activity determines a series of beneficial effects on health, including the possibility of counteracting the damage that is caused by arthritis to the cartilage of people suffering from osteoarthritis. Nevertheless, up to now, the studies that have taken into consideration the possible involvement of Irisin on the well-being of cartilage tissue are particularly limited. In this study, we postulated that the protective effect of physical activity on cartilage tissue may depend on the paracrine action of Irisin secreted during exercise; therefore, we analyzed the effects of Irisin, in vitro, on chondrogenic differentiation. To achieve this goal, three-dimensional cultures of commercially available human articular chondrocytes (HACs) were treated with the molecule under study. Our results revealed new crosstalk mechanisms between muscle and cartilage tissue. Furthermore, the confirmation of Irisin ability to induce chondrogenic differentiation could favor the development of exercise-mimetic drugs, with application relevance for patients who cannot perform physical activity. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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24 pages, 9056 KiB

Open AccessArticle

Combination of Poly(ε-Caprolactone) Biomaterials and Essential Oils to Achieve Anti-Bacterial and Osteo-Proliferative Properties for 3D-Scaffolds in Regenerative Medicine

by Sara Comini, Sara Scutera, Rosaria Sparti, Giuliana Banche, Bartolomeo Coppola, Cinzia Margherita Bertea, Gabriele Bianco, Noemi Gatti, Anna Maria Cuffini, Paola Palmero and Valeria Allizond

Pharmaceutics 2022, 14(9), 1873; https://doi.org/10.3390/pharmaceutics14091873 - 05 Sep 2022

Cited by 9 | Viewed by 1706

Abstract

Biomedical implants, an essential part of the medical treatments, still suffer from bacterial infections that hamper patients’ recovery and lives. Antibiotics are widely used to cure those infections but brought antibiotic resistance. Essential oils (EOs) demonstrate excellent antimicrobial activity and low resistance development risk. However, EO application in medicine is still quite scarce and almost no research work considers its use in combination with bioresorbable biomaterials, such as the poly(ε-caprolactone) (PCL) polymer. This work aimed to combine the antibacterial properties of EOs and their components, particularly eugenol and cinnamon oil, against Staphylococcus aureus, S. epidermidis and Escherichia coli, with those of PCL for medical applications in which good tissue regeneration and antimicrobial effects are required. The PCL porous scaffolds, added with increasing (from 30% to 50%) concentrations of eugenol and cinnamon oil, were characterized by square-shaped macropores. Saos-2 cells’ cell viability/proliferation was hampered by 40 and 50% EO-enriched PCL, whereas no cytotoxic effect was recorded for both 30% EO-added PCL and pure-PCL. The antibacterial tests revealed the presence of a small inhibition halo around the 30% eugenol and cinnamon oil-functionalized PCL scaffolds only for staphylococci, whereas a significant decrease on both adherent and planktonic bacteria was recorded for all the three microorganisms, thus proving that, even if the EOs are only in part released by the EO-added PCL scaffolds, an anti-adhesive feature is anyway achieved. The scaffold will have the ability to support new tissue formation and simultaneously will be able to prevent post-surgical infection. This research shows the great potential in the use of EOs or their single components, at low concentrations, for biomaterial functionalization with enhanced anti-bacterial and biointegration properties. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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Review

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21 pages, 900 KiB

Open AccessReview

Therapies Based on Adipose-Derived Stem Cells for Lower Urinary Tract Dysfunction: A Narrative Review

by Meng Liu, Jiasheng Chen, Nailong Cao, Weixin Zhao, Guo Gao, Ying Wang and Qiang Fu

Pharmaceutics 2022, 14(10), 2229; https://doi.org/10.3390/pharmaceutics14102229 - 19 Oct 2022

Viewed by 1513

Abstract

Lower urinary tract dysfunction often requires tissue repair or replacement to restore physiological functions. Current clinical treatments involving autologous tissues or synthetic materials inevitably bring in situ complications and immune rejection. Advances in therapies using stem cells offer new insights into treating lower urinary tract dysfunction. One of the most frequently used stem cell sources is adipose tissue because of its easy access, abundant source, low risk of severe complications, and lack of ethical issues. The regenerative capabilities of adipose-derived stem cells (ASCs) in vivo are primarily orchestrated by their paracrine activities, strong regenerative potential, multi-differentiation potential, and cell–matrix interactions. Moreover, biomaterial scaffolds conjugated with ASCs result in an extremely effective tissue engineering modality for replacing or repairing diseased or damaged tissues. Thus, ASC-based therapy holds promise as having a tremendous impact on reconstructive urology of the lower urinary tract. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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Other

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14 pages, 575 KiB

Open AccessSystematic Review

Why Use Adipose-Derived Mesenchymal Stem Cells in Tendinopathic Patients: A Systematic Review

by Annalisa Itro, Maria Consiglia Trotta, Roberta Miranda, Marco Paoletta, Annalisa De Cicco, Caterina Claudia Lepre, Umberto Tarantino, Michele D’Amico, Giuseppe Toro and Alfredo Schiavone Panni

Pharmaceutics 2022, 14(6), 1151; https://doi.org/10.3390/pharmaceutics14061151 - 27 May 2022

Cited by 6 | Viewed by 1986

Abstract

The aim of the present systematic review was to provide a clear overview of the clinical current research progress in the use of adipose-derived mesenchymal stem cells (ASCs) as an effective therapeutic option for the management of tendinopathies, pathologies clinically characterized by persistent mechanical pain and structural alteration of the tendons. The review was carried out using three databases (Scopus, ISI Web of Science and PubMed) and analyzed records from 2013 to 2021. Only English-language papers describing the isolation and manipulation of adipose tissue as source of ASCs and presenting ASCs as treatment for clinical tendinopathies were included. Overall, seven clinical studies met the inclusion criteria and met the minimum quality inclusion threshold. Data extraction and quality assessment were performed by groups of three reviewers. The available evidence showed the efficacy and safety of ASCs treatment for tendinopathies, although it lacked a clear description of the biomolecular mechanisms underlying the beneficial properties of ASCs. Full article

(This article belongs to the Special Issue Bio-Organic Materials for Tissue Engineering and Regenerative Medicine)

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