10th Anniversary of Biomedicines—Advances in Tendon and Bone Regeneration

A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Biomedical Engineering and Materials".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 7798

Special Issue Editors


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Guest Editor
Institute of Tendon and Bone Regeneration, Spinal Cord Injury & Tissue Regeneration Center Salzburg, Paracelsus Medical University, 5020 Salzburg, Austria
Interests: tendinopathy; tendon biology; tendon regeneration; bone regeneration

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Guest Editor
Experimental Trauma Surgery, Universitätsklinikum Jena, Klinik für Unfall-, Hand- und Wiederherstellungschirurgie, Am Klinikum 1, 07747 Jena, Germany
Interests: musculoskeletal tissue; mechanism of regeneration; molecular and cellular pathways; interaction with surrounding tissue and cells; preclinical models: in vitro and in vivo; regenerative therapies
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Special Issue Information

Dear Colleagues,

Injuries and degeneration of musculoskeletal tissues are generally not life-threatening diseases, but the main causes of pain, occupational disability and reduced quality of life are associated with high socio-economic costs. Therefore, elucidation of the underlying mechanisms of tissue degeneration and the development of innovative and transferable therapies to improve tissue regeneration are of great importance. This Special Issue is dedicated to the latest developments in the field of musculoskeletal degeneration and regeneration, with a focus on tendons and bone tissue. It will cover studies on the development of new preclinical models and detailed analyses of the underlying processes of tissue degeneration. The latest developments to improve musculoskeletal tissue regeneration will also be presented. We look forward to the submission of high-quality manuscripts on the topics mentioned and look forward to a very exciting Special Issue.

Prof. Dr. Andreas Traweger
Prof. Dr. Britt Wildemann
Guest Editors

Manuscript Submission Information

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Keywords

  • mechanism of musculoskeletal degeneration and regeneration
  • molecular and cellular pathways
  • preclinical in vitro and in vivo models
  • regenerative therapies
  • tendinopathy
  • biomaterials
  • tendon
  • bone

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Published Papers (4 papers)

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Research

19 pages, 6901 KiB  
Article
Dexamethasone Is Not Sufficient to Facilitate Tenogenic Differentiation of Dermal Fibroblasts in a 3D Organoid Model
by Niklas Kroner-Weigl, Jin Chu, Maximilian Rudert, Volker Alt, Chisa Shukunami and Denitsa Docheva
Biomedicines 2023, 11(3), 772; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines11030772 - 03 Mar 2023
Viewed by 1365
Abstract
Self-assembling three-dimensional organoids that do not rely on an exogenous scaffold but maintain their native cell-to-cell and cell-to-matrix interactions represent a promising model in the field of tendon tissue engineering. We have identified dermal fibroblasts (DFs) as a potential cell type for generating [...] Read more.
Self-assembling three-dimensional organoids that do not rely on an exogenous scaffold but maintain their native cell-to-cell and cell-to-matrix interactions represent a promising model in the field of tendon tissue engineering. We have identified dermal fibroblasts (DFs) as a potential cell type for generating functional tendon-like tissue. The glucocorticoid dexamethasone (DEX) has been shown to regulate cell proliferation and facilitate differentiation towards other mesenchymal lineages. Therefore, we hypothesized that the administration of DEX could reduce excessive DF proliferation and thus, facilitate the tenogenic differentiation of DFs using a previously established 3D organoid model combined with dose-dependent application of DEX. Interestingly, the results demonstrated that DEX, in all tested concentrations, was not sufficient to notably induce the tenogenic differentiation of human DFs and DEX-treated organoids did not have clear advantages over untreated control organoids. Moreover, high concentrations of DEX exerted a negative impact on the organoid phenotype. Nevertheless, the expression profile of tendon-related genes of untreated and 10 nM DEX-treated DF organoids was largely comparable to organoids formed by tendon-derived cells, which is encouraging for further investigations on utilizing DFs for tendon tissue engineering. Full article
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17 pages, 6568 KiB  
Article
Efficacy of an Antibiotic Loaded Ceramic-Based Bone Graft Substitute for the Treatment of Infected Non-Unions
by Holger Freischmidt, Jonas Armbruster, Catharina Rothhaas, Nadine Titze, Thorsten Guehring, Dennis Nurjadi, Jan Philippe Kretzer, Gerhard Schmidmaier, Paul Alfred Grützner and Lars Helbig
Biomedicines 2022, 10(10), 2513; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10102513 - 08 Oct 2022
Cited by 3 | Viewed by 1368
Abstract
The treatment of non-unions is often complicated by segmental bone defects and bacterial colonization. Because of the limited availability of autologous bone grafts, tissue engineering focuses on antibiotic-loaded bone graft substitutes. HACaS+G is a resorbable calcium sulphate-hydroxyapatite loaded with gentamicin. The osteoinductive, osteoconductive, [...] Read more.
The treatment of non-unions is often complicated by segmental bone defects and bacterial colonization. Because of the limited availability of autologous bone grafts, tissue engineering focuses on antibiotic-loaded bone graft substitutes. HACaS+G is a resorbable calcium sulphate-hydroxyapatite loaded with gentamicin. The osteoinductive, osteoconductive, and anti-infective effect of HACaS+G has already been demonstrated in clinical studies on patients with chronic osteomyelitis. However, especially for the treatment of infected non-unions with segmental bone defects by HACaS+G, reliable clinical testing is difficult and sufficient experimental data are lacking. We used an already established sequential animal model in infected and non-infected rat femora to investigate the osteoinductive, osteoconductive, and anti-infective efficacy of HACaS+G for the treatment of infected non-unions. In biomechanical testing, bone consolidation could not be observed under infected and non-infected conditions. Only a prophylactic effect against infections, but no eradication, could be verified in the microbiological analysis. Using µ-CT scans and histology, osteoinduction was detected in both the infected and non-infected bone, whereas osteoconduction occurred only in the non-infected setting. Our data showed that HACaS+G is osteoinductive, but does not have added benefits in infected non-unions in terms of osteoconduction and mechanical bone stability, especially in those with segmental bone defects. Full article
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16 pages, 1627 KiB  
Article
Age and Intrinsic Fitness Affect the Female Rotator Cuff Tendon Tissue
by Manuela Thierbach, Estelle Heyne, Michael Schwarzer, Lauren G. Koch, Steven L. Britton and Britt Wildemann
Biomedicines 2022, 10(2), 509; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020509 - 21 Feb 2022
Cited by 2 | Viewed by 1873
Abstract
The risk of the development of tendon disorders or ruptures increases with age, but it is unclear whether intrinsic fitness during lifetime might also affect tendon properties. To investigate this, a contrasting rat model of high-capacity runners (HCR with high intrinsic fitness) and [...] Read more.
The risk of the development of tendon disorders or ruptures increases with age, but it is unclear whether intrinsic fitness during lifetime might also affect tendon properties. To investigate this, a contrasting rat model of high-capacity runners (HCR with high intrinsic fitness) and low-capacity runners (LCR with low intrinsic fitness) was employed. Histological and molecular changes in rotator cuff (RC) tendons from 10 weeks old (young; HCR-10 and LCR-10) and 100 weeks old (old; HCR-100 and LCR-100) female rats were investigated. Age-dependent changes of RC tendons observed in HCR and LCR were increase of weight, decrease of tenocytes and RNA content, reduction of the wavy pattern of collagen and elastic fibers, repressed expression of Col1a1, Eln, Postn, Tnmd, Tgfb3 and Egr1 and reduction of the Col1:Col3 and Col1:Eln ratio. The LCR rats showed less physical activity, increased body weight, signs of metabolic disease and a reduced life expectancy. Their RC tendons revealed increased weight (more than age-dependent) and enlargement of the tenocyte nuclei (consistent with degenerative tendons). Low intrinsic fitness led to repressed expression of a further nine genes (Col3a1, Fbn1, Dcn, Tnc, Scx, Mkx, Bmp1, Tgfb1, Esr1) as well as the rise of the Col1:Col3 and Col1:Eln ratios (related to the lesser expression of Col3a1 and Eln). The intrinsic fitness influences the female RC tendons at least as much as age. Lower intrinsic fitness accelerates aging of RC tendons and leads to further impairment; this could result in decreased healing potential and elasticity and increased stiffness. Full article
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18 pages, 3988 KiB  
Article
Inhibition of Cdk5 Ameliorates Skeletal Bone Loss in Glucocorticoid-Treated Mice
by Benjamin Thilo Krüger, Lena Steppe, Sabine Vettorazzi, Melanie Haffner-Luntzer, Sooyeon Lee, Ann-Kristin Dorn, Anita Ignatius, Jan Tuckermann and Mubashir Ahmad
Biomedicines 2022, 10(2), 404; https://0-doi-org.brum.beds.ac.uk/10.3390/biomedicines10020404 - 08 Feb 2022
Cited by 4 | Viewed by 2448
Abstract
Glucocorticoids (GCs) are widely used to treat inflammatory diseases. However, their long-term use leads to glucocorticoid-induced osteoporosis, increasing morbidity and mortality. Both anabolic and anti-resorptive drugs are used to counteract GC-induced bone loss, however, they are expensive and/or have major side effects. Therefore, [...] Read more.
Glucocorticoids (GCs) are widely used to treat inflammatory diseases. However, their long-term use leads to glucocorticoid-induced osteoporosis, increasing morbidity and mortality. Both anabolic and anti-resorptive drugs are used to counteract GC-induced bone loss, however, they are expensive and/or have major side effects. Therefore, identifying new targets for cost-effective, small-molecule inhibitors is essential. We recently identified cyclin-dependent kinase 5 (Cdk5) as a suppressor of osteoblast differentiation and showed that its inhibition with roscovitine promoted osteoblastogenesis, thus improving the skeletal bone mass and fracture healing. Here, we assessed whether Cdk5 knockdown or inhibition could also reverse the GC-mediated suppression of osteoblast differentiation, bone loss, and fracture healing. We first demonstrated that Cdk5 silencing abolished the dexamethasone (Dex)-induced downregulation of alkaline phosphatase (Alp) activity, osteoblast-specific marker gene expression (Runx2, Sp7, Alpl, and Bglap), and mineralization. Similarly, Cdk5 inhibition rescued Dex-induced suppression of Alp activity. We further demonstrated that Cdk5 inhibition reversed prednisolone (Pred)-induced bone loss in mice, due to reduced osteoclastogenesis rather than improved osteoblastogenesis. Moreover, we revealed that Cdk5 inhibition failed to improve Pred-mediated impaired fracture healing. Taken together, we demonstrated that Cdk5 inhibition with roscovitine ameliorated GC-mediated bone loss but did not reverse GC-induced compromised fracture healing in mice. Full article
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