Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics

A special issue of Gels (ISSN 2310-2861). This special issue belongs to the section "Gel Applications".

Deadline for manuscript submissions: 30 July 2024 | Viewed by 12516

Special Issue Editors


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Guest Editor
Tissue Engineering, Orthopeadic Research & Mechanobiology, Department for BioMedical Research (DBMR), Medical Faculty, University of Bern, 3012 Bern, Switzerland
Interests: hydrogels; progenitor cells; regeneration; tissue engineering; bioreactors; mechanobiology; anterior cruciate ligament; cartilage; intervertebral disc; bone
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Guest Editor
Department of Chemical and Petroleum Engineering, Sharif University of Technology, Tehran, Iran
Interests: scaffolds for tissue engineering applications

Special Issue Information

Dear Colleagues,

Hydrogels for the regeneration or repair of tissues of the musculoskeletal apparatus in orthopedic research are of very high translational value. Various tissues of joint and joint-like tissues warrant applications of hydrogels. The best examples are the regeneration of articular cartilage of the knee or of the intervertebral disc (IVD) of the spine. These hydrogels need to be relatively stiff and should be very similar to native tissue in terms of mechanobiological parameters. In orthopedics, there is an urgent need to develop clinically feasible solutions to relieve pain and to restore the function of degenerated tissues such as the spine and other joints such as the rotator cuff of the shoulder. In the last few decades, smart biomaterials have been investigated which could be injected into degenerated IVD to restore disc height. This Special Issue seeks contributions to the field of engineered hydrogels for orthopedic applications that warrant mechanically reinforced properties by cross-linking and other means. These hydrogels will be targeted for cartilage repair and/or IVD, with a special focus on these micro-environments. These micro-environments warrant special reinforcements or specific adaptations for clinical applications. 

Prof. Dr. Benjamin Gantenbein
Prof. Dr. Mohammad Jafar Abdekhodaie
Guest Editors

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Keywords

  • biomaterials
  • 3D cell culture
  • alginate
  • micro-bead
  • cell viability
  • orthopedics
  • stem cells
  • regeneration
  • hyaluronic acid
  • collagen

Published Papers (6 papers)

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Research

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16 pages, 4356 KiB  
Article
Sulfated Hydrogels as Primary Intervertebral Disc Cell Culture Systems
by Paola Bermudez-Lekerika, Katherine B. Crump, Karin Wuertz-Kozak, Christine L. Le Maitre and Benjamin Gantenbein
Gels 2024, 10(5), 330; https://doi.org/10.3390/gels10050330 - 14 May 2024
Viewed by 637
Abstract
The negatively charged extracellular matrix plays a vital role in intervertebral disc tissues, providing specific cues for cell maintenance and tissue hydration. Unfortunately, suitable biomimetics for intervertebral disc regeneration are lacking. Here, sulfated alginate was investigated as a 3D culture material due to [...] Read more.
The negatively charged extracellular matrix plays a vital role in intervertebral disc tissues, providing specific cues for cell maintenance and tissue hydration. Unfortunately, suitable biomimetics for intervertebral disc regeneration are lacking. Here, sulfated alginate was investigated as a 3D culture material due to its similarity to the charged matrix of the intervertebral disc. Precursor solutions of standard alginate, or alginate with 0.1% or 0.2% degrees of sulfation, were mixed with primary human nucleus pulposus cells, cast, and cultured for 14 days. A 0.2% degree of sulfation resulted in significantly decreased cell density and viability after 7 days of culture. Furthermore, a sulfation-dependent decrease in DNA content and metabolic activity was evident after 14 days. Interestingly, no significant differences in cell density and viability were observed between surface and core regions for sulfated alginate, unlike in standard alginate, where the cell number was significantly higher in the core than in the surface region. Due to low cell numbers, phenotypic evaluation was not achieved in sulfated alginate biomaterial. Overall, standard alginate supported human NP cell growth and viability superior to sulfated alginate; however, future research on phenotypic properties is required to decipher the biological properties of sulfated alginate in intervertebral disc cells. Full article
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12 pages, 2474 KiB  
Article
Development of Improved Confined Compression Testing Setups for Use in Stress Relaxation Testing of Viscoelastic Biomaterials
by Anthony El Kommos, Alicia R. Jackson, Fotios Andreopoulos and Francesco Travascio
Gels 2024, 10(5), 329; https://doi.org/10.3390/gels10050329 - 13 May 2024
Viewed by 892
Abstract
The development of cell-based biomaterial alternatives holds significant promise in tissue engineering applications, but it requires accurate mechanical assessment. Herein, we present the development of a novel 3D-printed confined compression apparatus, fabricated using clear resin, designed to cater to the unique demands of [...] Read more.
The development of cell-based biomaterial alternatives holds significant promise in tissue engineering applications, but it requires accurate mechanical assessment. Herein, we present the development of a novel 3D-printed confined compression apparatus, fabricated using clear resin, designed to cater to the unique demands of biomaterial developers. Our objective was to enhance the precision of force measurements and improve sample visibility during compression testing. We compared the performance of our innovative 3D-printed confined compression setup to a conventional setup by performing stress relaxation testing on hydrogels with variable degrees of crosslinking. We assessed equilibrium force, aggregate modulus, and peak force. This study demonstrates that our revised setup can capture a larger range of force values while simultaneously improving accuracy. We were able to detect significant differences in force and aggregate modulus measurements of hydrogels with variable degrees of crosslinking using our revised setup, whereas these were indistinguishable with the convectional apparatus. Further, by incorporating a clear resin in the fabrication of the compression chamber, we improved sample visibility, thus enabling real-time monitoring and informed assessment of biomaterial behavior under compressive testing. Full article
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11 pages, 1541 KiB  
Article
The Injection of Gels Through an Intact Annulus Maintains Biomechanical Performance without Extrusion Risk
by Hans-Joachim Wilke, Holger Fuchs, Karin Benz, Juergen Mollenhauer, Christoph Gaissmaier, Frank Heuer and Cornelia Neidlinger-Wilke
Gels 2024, 10(4), 269; https://doi.org/10.3390/gels10040269 - 17 Apr 2024
Viewed by 871
Abstract
For autologous-disc-derived chondrocyte transplantation (ADCT) a transglutaminase crosslinked gelatine gel and an albumin hyaluronic acid gel, crosslinked with bis-thio-polyethylene glycol, were injected through a syringe into a degenerated intervertebral disc, where they solidified in situ. This biomechanical in vitro study with lumbar bovine [...] Read more.
For autologous-disc-derived chondrocyte transplantation (ADCT) a transglutaminase crosslinked gelatine gel and an albumin hyaluronic acid gel, crosslinked with bis-thio-polyethylene glycol, were injected through a syringe into a degenerated intervertebral disc, where they solidified in situ. This biomechanical in vitro study with lumbar bovine motion segments evaluated disc height changes, motion characteristics in a quasi-static spine loading simulators, and the potential extrusion risk of these biomaterials in a complex dynamic multi-axial loading set-up with 100,000 loading cycles. After the injection and formation of the gel in the center of the nucleus, the disc height increase was about 0.3 mm. During cyclic testing, a gradual decrease in height could be detected due to viscoelastic effects and fluid loss. No gel extrusion could be observed for all specimens during the entire test procedure. A macroscopic inspection after dissections showed an accumulation of the solidified gel in the center of the nucleus. The results demonstrate that the injection of in situ solidifying gels through the intact annulus allows for the stable maintenance of the injected gel at the target location, with high potential for use as a suitable scaffold to anchor therapeutically applied cells for disc regeneration within the treated nucleus pulposus. Full article
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23 pages, 14529 KiB  
Article
A Gellan Gum, Polyethylene Glycol, Hydroxyapatite Composite Scaffold with the Addition of Ginseng Derived Compound K with Possible Applications in Bone Regeneration
by Muthukumar Thangavelu, Pil-Yun Kim, Hunhwi Cho, Jeong-Eun Song, Sunjae Park, Alessio Bucciarelli and Gilson Khang
Gels 2024, 10(4), 257; https://doi.org/10.3390/gels10040257 - 10 Apr 2024
Viewed by 832
Abstract
Engineered bone scaffolds should mimic the natural material to promote cell adhesion and regeneration. For this reason, natural biopolymers are becoming a gold standard in scaffold production. In this study, we proposed a hybrid scaffold produced using gellan gum, hydroxyapatite, and Poly (ethylene [...] Read more.
Engineered bone scaffolds should mimic the natural material to promote cell adhesion and regeneration. For this reason, natural biopolymers are becoming a gold standard in scaffold production. In this study, we proposed a hybrid scaffold produced using gellan gum, hydroxyapatite, and Poly (ethylene glycol) within the addition of the ginseng compound K (CK) as a candidate for bone regeneration. The fabricated scaffold was physiochemically characterized. The morphology studied by scanning electron microscopy (SEM) and image analysis revealed a pore distribution suitable for cells growth. The addition of CK further improved the biological activity of the hybrid scaffold as demonstrated by the MTT assay. The addition of CK influenced the scaffold morphology, decreasing the mean pore diameter. These findings can potentially help the development of a new generation of hybrid scaffolds to best mimic the natural tissue. Full article
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19 pages, 4357 KiB  
Article
Evaluating the Efficacy of a Thermoresponsive Hydrogel for Delivering Anti-Collagen Antibodies to Reduce Posttraumatic Scarring in Orthopedic Tissues
by Andrzej Steplewski, Jolanta Fertala, Lan Cheng, Mark L. Wang, Michael Rivlin, Pedro Beredjiklian and Andrzej Fertala
Gels 2023, 9(12), 971; https://doi.org/10.3390/gels9120971 - 12 Dec 2023
Viewed by 1191
Abstract
Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical [...] Read more.
Excessive posttraumatic scarring in orthopedic tissues, such as joint capsules, ligaments, tendons, muscles, and peripheral nerves, presents a significant medical problem, resulting in pain, restricted joint mobility, and impaired musculoskeletal function. Current treatments for excessive scarring are often ineffective and require the surgical removal of fibrotic tissue, which can aggravate the problem. The primary component of orthopedic scars is collagen I-rich fibrils. Our research team has developed a monoclonal anti-collagen antibody (ACA) that alleviates posttraumatic scarring by inhibiting collagen fibril formation. We previously established the safety and efficacy of ACA in a rabbit-based arthrofibrosis model. In this study, we evaluate the utility of a well-characterized thermoresponsive hydrogel (THG) as a delivery vehicle for ACA to injury sites. Crucial components of the hydrogel included N-isopropylacrylamide, poly(ethylene glycol) diacrylate, and hyaluronic acid. Our investigation focused on in vitro ACA release kinetics, stability, and activity. Additionally, we examined the antigen-binding characteristics of ACA post-release from the THG in an in vivo context. Our preliminary findings suggest that the THG construct exhibits promise as a delivery platform for antibody-based therapeutics to reduce excessive scarring in orthopedic tissues. Full article
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Review

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27 pages, 744 KiB  
Review
Hydrogel-Based Strategies for Intervertebral Disc Regeneration: Advances, Challenges and Clinical Prospects
by Shivam U. Desai, Sai Sadhananth Srinivasan, Sangamesh Gurappa Kumbar and Isaac L. Moss
Gels 2024, 10(1), 62; https://doi.org/10.3390/gels10010062 - 15 Jan 2024
Viewed by 7480
Abstract
Millions of people worldwide suffer from low back pain and disability associated with intervertebral disc (IVD) degeneration. IVD degeneration is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and the annulus fibrosus (AF) fissures form, which often results in intervertebral disc [...] Read more.
Millions of people worldwide suffer from low back pain and disability associated with intervertebral disc (IVD) degeneration. IVD degeneration is highly correlated with aging, as the nucleus pulposus (NP) dehydrates and the annulus fibrosus (AF) fissures form, which often results in intervertebral disc herniation or disc space collapse and related clinical symptoms. Currently available options for treating intervertebral disc degeneration are symptoms control with therapy modalities, and/or medication, and/or surgical resection of the IVD with or without spinal fusion. As such, there is an urgent clinical demand for more effective disease-modifying treatments for this ubiquitous disorder, rather than the current paradigms focused only on symptom control. Hydrogels are unique biomaterials that have a variety of distinctive qualities, including (but not limited to) biocompatibility, highly adjustable mechanical characteristics, and most importantly, the capacity to absorb and retain water in a manner like that of native human nucleus pulposus tissue. In recent years, various hydrogels have been investigated in vitro and in vivo for the repair of intervertebral discs, some of which are ready for clinical testing. In this review, we summarize the latest findings and developments in the application of hydrogel technology for the repair and regeneration of intervertebral discs. Full article
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Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Title: Decellularized extracellular matrix based hydrogels for cartilage repair and regeneration
Authors: Jiangyao Xu, Sibylle Grad, Jeroen Geurts, Zhen Li
Affiliation: AO Research Institute Davos, Davos, Switzerland

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