Next Generation Bioengineered Strategies for Musculoskeletal Regeneration

A special issue of Bioengineering (ISSN 2306-5354). This special issue belongs to the section "Regenerative Engineering".

Deadline for manuscript submissions: closed (31 May 2023) | Viewed by 9809

Special Issue Editors


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Guest Editor
i3S, Institute for Research and Innovation in Health, University of Porto, Rua Alfredo Allen, 4200-135 Porto, Portugal
Interests: biosensors; organs-on-a-chip; vascularization; innervation; musculoskeletal interfaces; bioengineered microenvironments; gradient scaffolds; textile assembling; textured scaffolds; heterotypic cellular communication; disease modelling; soft and hard tissues

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Guest Editor
Department of Orthopedic Surgery, CHA Bundang Medical Center, School of Medicine, CHA University, Pocheon 13496, Gyeonggi-do, Korea
Interests: bone regeneration; osteoporosis; sarcopenia; mi-RNA

Special Issue Information

Dear Colleagues,

Cells are nature’s orchestraters and are known to sense the properties of their supporting environment at various scales. Remarkably, precise control over nano-to-macro bio-structural features of engineered materials is of major importance to recreate native key cues of the extracellular matrix. Advanced biomaterial design looks at controlling cellular responses to refine microenvironmental properties, paving the way to generate physiologically relevant niches and engineer soft-to-hard tissue interfaces. In recent years, several fabrication methods have enabled control over different interdependent biophysical parameters (e.g., topography, stiffness, elasticity, porosity). However, several challenges still emerge regarding the establishment of adequate “artificial” microenvironments capable of precisely replicating the health and disease states of tissues (e.g., biophysical, biochemical, biomechanical and biological properties) while monitoring the cellular responses in situ, thus compromising the transfer from the laboratory to pharma and clinic potential drug testing platforms or therapeutics. This Special Issue titled “Next-Generation Bioengineered Strategies for Musculoskeletal Regeneration” addresses the central role in defining proper bioengineered microenvironments and monitoring tools for the health and disease of musculoskeletal tissues. Therefore, contributions from worldwide studies on cell biology, on-chip technology, biosensing, bioprinting, bioreactor design and clinical translation of bioengineered solutions for musculoskeletal tissue and interface engineering and regeneration will be collected in this Special Issue.

Dr. Isabel Calejo
Dr. Soonchul Lee
Guest Editors

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Keywords

  • advanced cell culture systems
  • biosensing
  • bioengineered microenvironments
  • organs-on-a-chip
  • 3D printing
  • disease vs health modelling
  • bioreactors
  • drug testing platforms

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Published Papers (4 papers)

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Research

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15 pages, 41501 KiB  
Article
Using a Xenogeneic Acellular Dermal Matrix Membrane to Enhance the Reparability of Bone Marrow Mesenchymal Stem Cells for Cartilage Injury
by Weili Shi, Qingyang Meng, Xiaoqing Hu, Jin Cheng, Zhenxing Shao, Yuping Yang and Yingfang Ao
Bioengineering 2023, 10(8), 916; https://doi.org/10.3390/bioengineering10080916 - 2 Aug 2023
Cited by 3 | Viewed by 1467
Abstract
Due to its avascular organization and low mitotic ability, articular cartilage possesses limited intrinsic regenerative capabilities. The aim of this study is to achieve one-step cartilage repair in situ via combining bone marrow stem cells (BMSCs) with a xenogeneic Acellular dermal matrix (ADM) [...] Read more.
Due to its avascular organization and low mitotic ability, articular cartilage possesses limited intrinsic regenerative capabilities. The aim of this study is to achieve one-step cartilage repair in situ via combining bone marrow stem cells (BMSCs) with a xenogeneic Acellular dermal matrix (ADM) membrane. The ADM membranes were harvested from Sprague-Dawley (SD) rats through standard decellularization procedures. The characterization of the scaffolds was measured, including the morphology and physical properties of the ADM membrane. The in vitro experiments included the cell distribution, chondrogenic matrix quantification, and viability evaluation of the scaffolds. Adult male New Zealand white rabbits were used for the in vivo evaluation. Isolated microfracture was performed in the control (MF group) in the left knee and the tested ADM group was included as an experimental group when an ADM scaffold was implanted through matching with the defect after microfracture in the right knee. At 6, 12, and 24 weeks post-surgery, the rabbits were sacrificed for further research. The ADM could adsorb water and had excellent porosity. The bone marrow stem cells (BMSCs) grew well when seeded on the ADM scaffold, demonstrating a characteristic spindle-shaped morphology. The ADM group exhibited an excellent proliferative capacity as well as the cartilaginous matrix and collagen production of the BMSCs. In the rabbit model, the ADM group showed earlier filling, more hyaline-like neo-tissue formation, and better interfacial integration between the defects and normal cartilage compared with the microfracture (MF) group at 6, 12, and 24 weeks post-surgery. In addition, neither intra-articular inflammation nor a rejection reaction was observed after the implantation of the ADM scaffold. This study provides a promising biomaterial-based strategy for cartilage repair and is worth further investigation in large animal models. Full article
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11 pages, 1107 KiB  
Article
Outcomes Using Focused Shockwave for Treatment of Bone Stress Injury in Runners
by Alexandra Beling, Amol Saxena, Karsten Hollander and Adam S. Tenforde
Bioengineering 2023, 10(8), 885; https://doi.org/10.3390/bioengineering10080885 - 25 Jul 2023
Cited by 4 | Viewed by 2678
Abstract
Bone stress injury (BSI) is a common overuse injury that can result in prolonged time away from sport. Limited studies have characterized the use of extracorporeal shockwave therapy (ESWT) for the treatment of BSI. The purpose of this study was to describe the [...] Read more.
Bone stress injury (BSI) is a common overuse injury that can result in prolonged time away from sport. Limited studies have characterized the use of extracorporeal shockwave therapy (ESWT) for the treatment of BSI. The purpose of this study was to describe the use of ESWT for the management of BSI in runners. A retrospective chart review was performed to identify eligible patients in a single physician’s clinic from 1 August 2018 to 30 September 2022. BSI was identified in 40 runners with 41 injuries (28 females; average age and standard deviation: 30 ± 13 years; average pre-injury training 72 ± 40 km per week). Overall, 63% (n = 26) met the criteria for moderate- or high-risk Female or Male Athlete Triad categories. Runners started ESWT at a median of 36 days (IQR 11 to 95 days; range 3 days to 8 years) from BSI diagnosis. On average, each received 5 ± 2 total focused ESWT treatments. Those with acute BSI (ESWT started <3 months from BSI diagnosis) had an average return to run at 12.0 ± 7.5 weeks, while patients with delayed union (>3 months, n = 3) or non-union (>6 months, n = 9) had longer time for return to running (19.8 ± 14.8 weeks, p = 0.032). All runners returned to pain-free running after ESWT except one runner with non-union of grade 4 navicular BSI who opted for surgery. No complications were observed with ESWT. These findings suggest that focused ESWT may be a safe treatment for the management of BSI in runners. Full article
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19 pages, 2647 KiB  
Article
Vancomycin-Loaded, Nanohydroxyapatite-Based Scaffold for Osteomyelitis Treatment: In Vivo Rabbit Toxicological Tests and In Vivo Efficacy Tests in a Sheep Model
by Nuno Alegrete, Susana R. Sousa, Tatiana Padrão, Ângela Carvalho, Raquel Lucas, Raphael F. Canadas, Catarina Lavrador, Nuno Alexandre, Fátima Gärtner, Fernando J. Monteiro and Manuel Gutierres
Bioengineering 2023, 10(2), 206; https://doi.org/10.3390/bioengineering10020206 - 4 Feb 2023
Cited by 7 | Viewed by 2389
Abstract
The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as [...] Read more.
The treatment for osteomyelitis consists of surgical debridement, filling of the dead space, soft tissue coverage, and intravenous administration of antimicrobial (AM) agents for long periods. Biomaterials for local delivery of AM agents, while providing controllable antibiotic release rates and simultaneously acting as a bone scaffold, may be a valuable alternative; thus, avoiding systemic AM side effects. V-HEPHAPC is a heparinized nanohydroxyapatite (nHA)/collagen biocomposite loaded with vancomycin that has been previously studied and tested in vitro. It enables a vancomycin-releasing profile with an intense initial burst, followed by a sustained release with concentrations above the Minimum Inhibitory Concentration (MIC) for MRSA. In vitro results have also shown that cellular viability is not compromised, suggesting that V-HEPHAPC granules may be a promising alternative device for the treatment of osteomyelitis. In the present study, V-HEPHAPC (HEPHAPC with vancomycin) granules were used as a vancomycin carrier to treat MRSA osteomyelitis. First, in vivo Good Laboratory Practice (GLP) toxicological tests were performed in a rabbit model, assuring that HEPHAPC and V-HEPHAPC have no relevant side effects. Second, V-HEPHAPC proved to be an efficient drug carrier and bone substitute to control MRSA infection and simultaneously reconstruct the bone cavity in a sheep model. Full article
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Review

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14 pages, 1290 KiB  
Review
The Role of the Innate Immune System in Wear Debris-Induced Inflammatory Peri-Implant Osteolysis in Total Joint Arthroplasty
by John Patrick Connors, John W. Stelzer, Patrick M. Garvin, Ian J. Wellington and Olga Solovyova
Bioengineering 2022, 9(12), 764; https://doi.org/10.3390/bioengineering9120764 - 4 Dec 2022
Cited by 6 | Viewed by 2381
Abstract
Periprosthetic osteolysis remains a leading complication of total hip and knee arthroplasty, often resulting in aseptic loosening of the implant and necessitating revision surgery. Wear-induced particulate debris is the main cause initiating this destructive process. The purpose of this article is to review [...] Read more.
Periprosthetic osteolysis remains a leading complication of total hip and knee arthroplasty, often resulting in aseptic loosening of the implant and necessitating revision surgery. Wear-induced particulate debris is the main cause initiating this destructive process. The purpose of this article is to review recent advances in understanding of how wear debris causes osteolysis, and emergent strategies for the avoidance and treatment of this disease. A strong activator of the peri-implant innate immune this debris-induced inflammatory cascade is dictated by macrophage secretion of TNF-α, IL-1, IL-6, and IL-8, and PGE2, leading to peri-implant bone resorption through activation of osteoclasts and inhibition of osteoblasts through several mechanisms, including the RANK/RANKL/OPG pathway. Therapeutic agents against proinflammatory mediators, such as those targeting tumor necrosis factor (TNF), osteoclasts, and sclerostin, have shown promise in reducing peri-implant osteolysis in vitro and in vivo; however, radiographic changes and clinical diagnosis often lag considerably behind the initiation of osteolysis, making timely treatment difficult. Considerable efforts are underway to develop such diagnostic tools, therapies, and identify novel targets for therapeutic intervention. Full article
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