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Pharmaceuticals
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Cell-Based Therapies for Bone and Cartilage Regeneration
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Cell-Based Therapies for Bone and Cartilage Regeneration

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Biopharmaceuticals".

Deadline for manuscript submissions: closed (24 December 2021) | Viewed by 27302

Special Issue Editors

Dr. Madhu S. Dhar

E-Mail Website
Guest Editor
Department of Large Animal Clinical Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, TN 37996, USA
Interests: regenerative medicine; cell biology; nanoparticles
Special Issues, Collections and Topics in MDPI journals
Dr. Austin Bow

E-Mail Website
Guest Editor
The University of Tennessee, Knoxville, TN, USA
Interests: regenerative medicine; stem cells; biomaterials

Special Issue Information

The concept of tissue engineering was put forth roughly two decades ago, and has undergone rapid evolution due to the progress in biomaterial development and stem cell research. Tissue engineering refers to the combination of biomaterials, cells (progenitor/stem cells), and biologically active molecules (growth factors and small molecules) to stimulate the repair and restoration of functionally damaged tissues. Regenerative medicine encompasses tissue engineering as well as research on self-healing, in which the body uses its own systems to repair tissues and organs. The terms “tissue engineering” and “regenerative medicine” have become largely interchangeable.

When a novel biomaterial or a biomaterial-cell-based technology is fabricated for bone and cartilage regeneration and repair, their interaction with progenitor cells is vital to an effective clinical outcome. Despite the importance of evaluating these technologies in an in vitro setting, a critical assessment must be made utilizing an in vivo system to demonstrate both biocompatibility and regenerative function. In particular, the biomaterial–cell interface is crucial to effective tissue regeneration. In vivo studies examining naturally occurring diseases and injuries or controlled animal models contribute substantially to the progress of tissue engineering.

This Special Issue aims to report recent advances in using cell-based therapies for bone and cartilage regeneration.  Original research articles, review articles, and clinical studies on the in vivo application of multipotent and pluripotent stem cells, nanoparticles, or their combination for the treatment of bone and cartilage defects are welcome in this Special Issue.

Potential topics include but are not limited to the following:

  • in vivo animal models of bone and cartilage injuries and diseases;
  • in vivo animal models where multipotent and pluripotent stem cells are utilized;
  • in vivo animal models well-established for bone and cartilage injuries/diseases;
  • biomaterial design and characterization for bone and cartilage differentiation of stem cells as therapeutic modalities; and
  • applications of tissue-engineered scaffolds for bone and cartilage tissue regeneration.

Dr. Madhu S. Dhar
Dr. Austin Bow
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. Pharmaceuticals 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

  • regenerative medicine
  • nanoparticles
  • cell biology
  • biomaterial
  • cartilage
  • bone
  • cell-based therapies
  • tissue engineering
  • multipotent stem cells
  • pluripotent stem cells

Published Papers (6 papers)

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Research

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17 pages, 96674 KiB  
Article
Human Salivary Histatin-1-Functionalized Gelatin Methacrylate Hydrogels Promote the Regeneration of Cartilage and Subchondral Bone in Temporomandibular Joints
by Changjing Shi, Yu Yao, Lei Wang, Ping Sun, Jianying Feng and Gang Wu
Pharmaceuticals 2021, 14(5), 484; https://doi.org/10.3390/ph14050484 - 19 May 2021
Cited by 6 | Viewed by 2972
Abstract
The avascular structure and lack of regenerative cells make the repair of osteochondral defects in the temporomandibular joint (TMJ) highly challenging in the clinic. To provide a viable treatment option, we developed a methacrylated gelatin (Gel-MA) hydrogel functionalized with human salivary histatin-1 (Hst1). [...] Read more.
The avascular structure and lack of regenerative cells make the repair of osteochondral defects in the temporomandibular joint (TMJ) highly challenging in the clinic. To provide a viable treatment option, we developed a methacrylated gelatin (Gel-MA) hydrogel functionalized with human salivary histatin-1 (Hst1). Gel-MA is highly biocompatible, biodegradable, and cost-effective. Hst1 is capable of activating a series of cell activities, such as adhesion, migration, differentiation, and angiogenesis. To evaluate the efficacy of Hst1/Gel-MA, critical-size osteochondral defects (3 mm in diameter and 3 mm in depth) of TMJ in New Zealand white rabbits were surgically created and randomly assigned to one of the three treatment groups: (1) control (no filling material); (2) Gel-MA hydrogel; (3) Hst1/Gel-MA hydrogel. Samples were retrieved 1, 2, and 4 weeks post-surgery and subjected to gross examination and a series of histomorphometric and immunological analyses. In comparison with the control and Gel-MA alone groups, Hst1/Gel-MA hydrogel was associated with significantly higher International Cartilage Repair Society score, modified O’Driscoll score, area percentages of newly formed bone, cartilage, collagen fiber, and glycosaminoglycan, and expression of collagen II and aggrecan. In conclusion, Hst1/Gel-MA hydrogels significantly enhance bone and cartilage regeneration, thus bearing promising application potential for repairing osteochondral defects. Full article
(This article belongs to the Special Issue Cell-Based Therapies for Bone and Cartilage Regeneration)
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14 pages, 3133 KiB  
Article
The Embryonic Chick Femur Organotypic Model as a Tool to Analyze the Angiotensin II Axis on Bone Tissue
by Thais Francini Garbieri, Victor Martin, Carlos Ferreira Santos, Pedro de Sousa Gomes and Maria Helena Fernandes
Pharmaceuticals 2021, 14(5), 469; https://doi.org/10.3390/ph14050469 - 16 May 2021
Cited by 5 | Viewed by 2251
Abstract
Activation of renin–angiotensin system (RAS) plays a role in bone deterioration associated with bone metabolic disorders, via increased Angiotensin II (AngII) targeting Angiotensin II type 1 receptor/Angiotensin II type 2 receptor (AT1R/AT2R). Despite the wide data availability, the RAS role remains controversial. This [...] Read more.
Activation of renin–angiotensin system (RAS) plays a role in bone deterioration associated with bone metabolic disorders, via increased Angiotensin II (AngII) targeting Angiotensin II type 1 receptor/Angiotensin II type 2 receptor (AT1R/AT2R). Despite the wide data availability, the RAS role remains controversial. This study analyzes the feasibility of using the embryonic chick femur organotypic model to address AngII/AT1R/AT2R axis in bone, which is an application not yet considered. Embryonic day-11 femurs were cultured ex vivo for 11 days in three settings: basal conditions, exposure to AngII, and modulation of AngII effects by prior receptor blockade, i.e., AT1R, AT2R, and AT1R + AT2R. Tissue response was evaluated by combining µCT and histological analysis. Basal-cultured femurs expressed components of RAS, namely ACE, AT1R, AT2R, and MasR (qPCR analysis). Bone formation occurred in the diaphyseal region in all conditions. In basal-cultured femurs, AT1R blocking increased Bone Surface/Bone Volume (BS/BV), whereas Bone Volume/Tissue Volume (BV/TV) decreased with AT2R or AT1R + AT2R blockade. Exposure to AngII greatly decreased BV/TV compared to basal conditions. Receptor blockade prior to AngII addition prevented this effect, i.e., AT1R blockade induced BV/TV, whereas blocking AT2R caused lower BV/TV increase but greater BS/BV; AT1R + AT2R blockade also improved BV/TV. Concluding, the embryonic chick femur model was sensitive to three relevant RAS research setups, proving its usefulness to address AngII/AT1R/AT2R axis in bone both in basal and activated conditions. Full article
(This article belongs to the Special Issue Cell-Based Therapies for Bone and Cartilage Regeneration)
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Review

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16 pages, 812 KiB  
Review
Lineage Differentiation Potential of Different Sources of Mesenchymal Stem Cells for Osteoarthritis Knee
by Gollahalli Shivashankar Prajwal, Naveen Jeyaraman, Krishna Kanth V, Madhan Jeyaraman, Sathish Muthu, Sree Naga Sowndary Rajendran, Ramya Lakshmi Rajendran, Manish Khanna, Eun Jung Oh, Kang Young Choi, Ho Yun Chung, Byeong-Cheol Ahn and Prakash Gangadaran
Pharmaceuticals 2022, 15(4), 386; https://doi.org/10.3390/ph15040386 - 22 Mar 2022
Cited by 5 | Viewed by 3831
Abstract
Tissue engineering and regenerative medicine (TERM) have paved a way for treating musculoskeletal diseases in a minimally invasive manner. The regenerative medicine cocktail involves the usage of mesenchymal stem/stromal cells (MSCs), either uncultured or culture-expanded cells along with growth factors, cytokines, exosomes, and [...] Read more.
Tissue engineering and regenerative medicine (TERM) have paved a way for treating musculoskeletal diseases in a minimally invasive manner. The regenerative medicine cocktail involves the usage of mesenchymal stem/stromal cells (MSCs), either uncultured or culture-expanded cells along with growth factors, cytokines, exosomes, and secretomes to provide a better regenerative milieu in degenerative diseases. The successful regeneration of cartilage depends on the selection of the appropriate source of MSCs, the quality, quantity, and frequency of MSCs to be injected, and the selection of the patient at an appropriate stage of the disease. However, confirmation on the most favorable source of MSCs remains uncertain to clinicians. The lack of knowledge in the current cellular treatment is uncertain in terms of how beneficial MSCs are in the long-term or short-term (resolution of pain) and improved quality of life. Whether MSCs treatments have any superiority, exists due to sources of MSCs utilized in their potential to objectively regenerate the cartilage at the target area. Many questions on source and condition remain unanswered. Hence, in this review, we discuss the lineage differentiation potentials of various sources of MSCs used in the management of knee osteoarthritis and emphasize the role of tissue engineering in cartilage regeneration. Full article
(This article belongs to the Special Issue Cell-Based Therapies for Bone and Cartilage Regeneration)
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15 pages, 3884 KiB  
Review
Osteogenic and Chondrogenic Potential of Periosteum-Derived Mesenchymal Stromal Cells: Do They Hold the Key to the Future?
by Madhan Jeyaraman, Sathish Muthu, Prakash Gangadaran, Rajni Ranjan, Naveen Jeyaraman, Gollahalli Shivashankar Prajwal, Prabhu Chandra Mishra, Ramya Lakshmi Rajendran and Byeong-Cheol Ahn
Pharmaceuticals 2021, 14(11), 1133; https://doi.org/10.3390/ph14111133 - 08 Nov 2021
Cited by 9 | Viewed by 7277
Abstract
The periosteum, with its outer fibrous and inner cambium layer, lies in a dynamic environment with a niche of pluripotent stem cells for their reparative needs. The inner cambium layer is rich in mesenchymal progenitors, osteogenic progenitors, osteoblasts, and fibroblasts in a scant [...] Read more.
The periosteum, with its outer fibrous and inner cambium layer, lies in a dynamic environment with a niche of pluripotent stem cells for their reparative needs. The inner cambium layer is rich in mesenchymal progenitors, osteogenic progenitors, osteoblasts, and fibroblasts in a scant collagen matrix environment. Their role in union and remodeling of fracture is well known. However, the periosteum as a source of mesenchymal stem cells has not been explored in detail. Moreover, with the continuous expansion of techniques, newer insights have been acquired into the roles and regulation of these periosteal cells. From a therapeutic standpoint, the periosteum as a source of tissue engineering has gained much attraction. Apart from its role in bone repair, analysis of the bone-forming potential of periosteum-derived stem cells is lacking. Hence, this article elucidates the role of the periosteum as a potential source of mesenchymal stem cells along with their capacity for osteogenic and chondrogenic differentiation for therapeutic application in the future. Full article
(This article belongs to the Special Issue Cell-Based Therapies for Bone and Cartilage Regeneration)
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19 pages, 5567 KiB  
Review
Silica-Based Bioactive Glasses and Their Applications in Hard Tissue Regeneration: A Review
by Nuha Al-Harbi, Hiba Mohammed, Yas Al-Hadeethi, Ahmed Samir Bakry, Ahmad Umar, Mahmoud Ali Hussein, Mona Aly Abbassy, Karthik Gurunath Vaidya, Ghada Al Berakdar, Elmoiz Merghni Mkawi and Manasa Nune
Pharmaceuticals 2021, 14(2), 75; https://doi.org/10.3390/ph14020075 - 20 Jan 2021
Cited by 64 | Viewed by 5693
Abstract
Regenerative medicine is a field that aims to influence and improvise the processes of tissue repair and restoration and to assist the body to heal and recover. In the field of hard tissue regeneration, bio-inert materials are being predominantly used, and there is [...] Read more.
Regenerative medicine is a field that aims to influence and improvise the processes of tissue repair and restoration and to assist the body to heal and recover. In the field of hard tissue regeneration, bio-inert materials are being predominantly used, and there is a necessity to use bioactive materials that can help in better tissue–implant interactions and facilitate the healing and regeneration process. One such bioactive material that is being focused upon and studied extensively in the past few decades is bioactive glass (BG). The original bioactive glass (45S5) is composed of silicon dioxide, sodium dioxide, calcium oxide, and phosphorus pentoxide and is mainly referred to by its commercial name Bioglass. BG is mainly used for bone tissue regeneration due to its osteoconductivity and osteostimulation properties. The bioactivity of BG, however, is highly dependent on the compositional ratio of certain glass-forming system content. The manipulation of content ratio and the element compositional flexibility of BG-forming network developed other types of bioactive glasses with controllable chemical durability and chemical affinity with bone and bioactivity. This review article mainly discusses the basic information about silica-based bioactive glasses, including their composition, processing, and properties, as well as their medical applications such as in bone regeneration, as bone grafts, and as dental implant coatings. Full article
(This article belongs to the Special Issue Cell-Based Therapies for Bone and Cartilage Regeneration)
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Other

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25 pages, 2411 KiB  
Systematic Review
Adipose Tissue-Derived Mesenchymal Stem Cells as a Potential Restorative Treatment for Cartilage Defects: A PRISMA Review and Meta-Analysis
by Henry Yue-Hong Meng, Victor Lu and Wasim Khan
Pharmaceuticals 2021, 14(12), 1280; https://doi.org/10.3390/ph14121280 - 08 Dec 2021
Cited by 15 | Viewed by 4197
Abstract
Cartilage defects are a predisposing factor for osteoarthritis. Conventional therapies are mostly palliative and there is an interest in developing newer therapies that target the disease’s progression. Mesenchymal stem cells (MSCs) have been suggested as a promising therapy to restore hyaline cartilage to [...] Read more.
Cartilage defects are a predisposing factor for osteoarthritis. Conventional therapies are mostly palliative and there is an interest in developing newer therapies that target the disease’s progression. Mesenchymal stem cells (MSCs) have been suggested as a promising therapy to restore hyaline cartilage to cartilage defects, though the optimal cell source has remained under investigation. A PRISMA systematic review was conducted utilising five databases (MEDLINE, EMBASE, Cochrane Library, Scopus, Web of Science) which identified nineteen human studies that used adipose tissue-derived MSC (AMSC)-based therapies, including culture-expanded AMSCs and stromal vascular fraction, to treat cartilage defects. Clinical, imaging and histological outcomes, as well as other relevant details pertaining to cartilage regeneration, were extracted from each study. Pooled analysis revealed a significant improvement in WOMAC scores (mean difference: −25.52; 95%CI (−30.93, −20.10); p < 0.001), VAS scores (mean difference: −3.30; 95%CI (−3.72, −2.89); p < 0.001), KOOS scores and end point MOCART score (mean: 68.12; 95%CI (62.18, 74.05)), thus showing improvement. The studies in this review demonstrate the safety and efficacy of AMSC-based therapies for cartilage defects. Establishing standardised methods for MSC extraction and delivery, and performing studies with long follow-up should enable future high-quality research to provide the evidence needed to bring AMSC-based therapies into the market. Full article
(This article belongs to the Special Issue Cell-Based Therapies for Bone and Cartilage Regeneration)
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