Gels | Special Issue : Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics

Research

17 pages, 5565 KiB

Open AccessArticle

Papain Injection Creates a Nucleotomy-like Cavity for Testing Gels in Intervertebral Discs

by Jan Ulrich Jansen, Graciosa Quelhas Teixeira, Andrea Vernengo, Sybille Grad, Cornelia Neidlinger-Wilke and Hans-Joachim Wilke

Gels 2024, 10(9), 571; https://doi.org/10.3390/gels10090571 - 2 Sep 2024

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Abstract

Biomaterials, such as hydrogels, have an increasingly important role in the development of regenerative approaches for the intervertebral disc. Since animal models usually resist biomaterial injection due to high intradiscal pressure, preclinical testing of the biomechanical performance of biomaterials after implantation remains difficult. [...] Read more.

Biomaterials, such as hydrogels, have an increasingly important role in the development of regenerative approaches for the intervertebral disc. Since animal models usually resist biomaterial injection due to high intradiscal pressure, preclinical testing of the biomechanical performance of biomaterials after implantation remains difficult. Papain reduces the intradiscal pressure, creates cavities within the disc, and allows for biomaterial injections. But papain digestion needs time, and cadaver experiments that are limited to 24 h for measuring range of motion (ROM) cannot not be combined with papain digestion just yet. In this study, we successfully demonstrate a new organ culture approach, facilitating papain digestion to create cavities in the disc and the testing of ROM, neutral zone (NZ), and disc height. Papain treatment increased the ROM by up to 109.5%, extended NZ by up to 210.9%, and decreased disc height by 1.96 ± 0.74 mm. A median volume of 0.73 mL hydrogel could be injected after papain treatment, and histology revealed a strong loss of proteoglycans in the remaining nucleus tissue. Papain has the same biomechanical effects as known from nucleotomies or herniations and thus creates a disc model to study such pathologies in vitro. This new model can now be used to test the performance of biomaterials. Full article

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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16 pages, 3911 KiB

Open AccessArticle

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

Cited by 1 | Viewed by 1273 | Correction

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

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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12 pages, 2474 KiB

Open AccessArticle

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 1591

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

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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11 pages, 1541 KiB

Open AccessArticle

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

Cited by 3 | Viewed by 1244

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

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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23 pages, 14529 KiB

Open AccessArticle

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 1335

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

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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19 pages, 4357 KiB

Open AccessArticle

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

Cited by 1 | Viewed by 1540

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

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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Review

Jump to: Research, Other

42 pages, 7942 KiB

Open AccessReview

Hydrogel Use in Osteonecrosis of the Femoral Head

by Zeynep Bal and Nobuyuki Takakura

Gels 2024, 10(8), 544; https://doi.org/10.3390/gels10080544 - 22 Aug 2024

Viewed by 980

Abstract

Osteonecrosis of the femoral head (ONFH) is a vascular disease of unknown etiology and can be categorized mainly into two types: non-traumatic and traumatic ONFH. Thus, understanding osteogenic–angiogenic coupling is of prime importance in finding a solution for the treatment of ONFH. Hydrogels [...] Read more.

Osteonecrosis of the femoral head (ONFH) is a vascular disease of unknown etiology and can be categorized mainly into two types: non-traumatic and traumatic ONFH. Thus, understanding osteogenic–angiogenic coupling is of prime importance in finding a solution for the treatment of ONFH. Hydrogels are biomaterials that are similar to the extracellular matrix (ECM). As they are able to mimic real tissue, they meet one of the most important rules in tissue engineering. In ONFH studies, hydrogels have recently become popular because of their ability to retain water and their adjustable properties, injectability, and mimicry of natural ECM. Because bone regeneration and graft materials are very broad areas of research and ONFH is a complex situation including bone and vascular systems, and there is no settled treatment strategy for ONFH worldwide, in this review paper, we followed a top-down approach by reviewing (1) bone and bone grafting, (2) hydrogels, (3) vascular systems, and (4) ONFH and hydrogel use in ONFH with studies in the literature which show promising results in limited clinical studies. The aim of this review paper is to provide the reader with general information on every aspect of ONFH and to focus on the hydrogel used in ONFH. Full article

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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27 pages, 744 KiB

Open AccessReview

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

Cited by 4 | Viewed by 8918

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

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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Other

Jump to: Research, Review

2 pages, 369 KiB

Open AccessCorrection

Correction: Bermudez-Lekerika et al. Sulfated Hydrogels as Primary Intervertebral Disc Cell Culture Systems. Gels 2024, 10, 330

by Paola Bermudez-Lekerika, Katherine B. Crump, Karin Wuertz-Kozak, Christine L. Le Maitre and Benjamin Gantenbein

Gels 2024, 10(10), 612; https://doi.org/10.3390/gels10100612 - 24 Sep 2024

Viewed by 281

Abstract

In the original publication [...] Full article

(This article belongs to the Special Issue Hydrogels for the Regeneration of Joints of the Musculoskeletal System in Orthopedics)

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