Effects of Ultra-Purified Alginate Gel Implantation on Meniscal Defects in Rabbits

Abstract

Background: Many tissue-engineered methods for meniscal repair have been studied, but their utility remains unclear. Hypothesis: Implantation of low-endotoxin, ultra-purified alginate (UPAL) gel without cells could induce fibrocartilage regeneration on meniscal defects in rabbits. Study Design: Controlled laboratory study. Methods: Forty-two mature Japanese White rabbits were divided into 2 groups of 21 animals each. In each animal, a cylindrical defect measuring 2 mm in diameter was created with a biopsy punch on the anterior horn of the medial meniscus. In the control group, no treatment was applied on the left medial meniscal defect. In the UPAL gel group, the right medial meniscal defect was injected with the UPAL gel and gelated by a CaCl2 solution. Samples were evaluated at 3, 6, and 12 weeks postoperatively. For biomechanical evaluation, 6 additional samples from intact animals were used for comparison. Results: The macroscopic score was significantly greater in the UPAL gel group than in the control group at 3 weeks (mean ± SE: 5.6 ± 0.82 vs 3.4 ± 0.83, P = .010), 6 weeks (5.9 ± 0.72 vs 2.5 ± 0.75, P = .026), and 12 weeks (5.2 ± 1.21 vs 1.0 ± 0.63, P = .020). The histological score was significantly greater in the UPAL group than in the control group at 3 weeks (2.1 ± 0.31 vs 1.2 ± 0.25, P = .029) and 12 weeks (2.2 ± 0.55 vs 0.3 ± 0.21, P = .016). The mean stiffness of the reparative tissue in the UPAL gel group was significantly greater than that in the control group at 6 weeks (24.325 ± 3.920 N/mm vs 8.723 ± 1.190 N/mm, P = .006) and at 12 weeks (27.804 ± 6.169 N/mm vs not applicable [because of rupture]). Conclusion: The UPAL gel enhanced the spontaneous repair of fibrocartilage tissues in a cylindrical meniscal defect in rabbits. Clinical Relevance: These results imply that the acellular UPAL gel may improve the repair of traumatic meniscal injuries.

Acellular Cartilage Repair Technique Based on Ultrapurified Alginate Gel Implantation for Advanced Capitellar Osteochondritis Dissecans

“… 13 Initial studies of implantation of this alginate reported no infections or allergic reactions in rabbit and canine models. 19 , 40 The low endotoxin level enables safe clinical application of the UPAL gel because it does not induce immunologic reactions to the implanted material. 11 , 14 The current clinical and radiographic findings suggested that no infections or allergic reactions occurred in any of the 5 patients.…”

Meniscal Regenerative Scaffolds Based on Biopolymers and Polymers: Recent Status and Applications

“…Alginate, obtained from brown algae, is an anionic polysaccharide that exhibits remarkably good scaffold-forming properties and is biocompatible, inexpensive and abundant ( Lee and Mooney, 2012 ). Furthermore, alginate hydrogels can be crosslinked by various materials (e.g., Ca 2+ ) for bioactive agents and cell delivery ( Lee and Mooney, 2012 ; Venkatesan et al, 2015 ; Kim et al, 2019 ). By combining collagen, alginate (A) and oxidized alginate (ADA), Gupta’s group designed self-healing interpenetrating network (IPN) hydrogel-loaded scaffolds with dual crosslinking [Ca 2+ -based ionic crosslinking and Schiff base reaction crosslinking (A-A, A-ADA)] capabilities, which revealed great potential for supporting fibrochondrocyte behavior and chondrogenesis in vitro ( Gupta et al, 2020a ).…”

Advanced Polymer-Based Drug Delivery Strategies for Meniscal Regeneration

“…77,78 Alginate hydrogels can be easily crosslinked by various materials (e.g., Ca 2+ ) for bioactive agent and cell delivery. 61,62,79 At different molar ratios, chitosan was successfully crosslinked with polyvinyl alcohol using urethane prepolymer chains. 80 Another strategy is to use combinational approaches.…”

“…The reparative tissue in the UPAL gel group exhibited superior stiffness (27.8 -6.2 N/mm) after 12 weeks. 62 In addition to their role as conventional tissue engineering constructs, as DDSs, natural polymers can be easily fabricated as hydrogels, microcarriers, 3D scaffolds, and fibers. For example, considering the necessity of the chondrogenesis of stem cells in meniscal repair and regeneration, Deng et al 87 incorporated HA into poly-D,L-lactic acid/polyethylene glycol/poly-D,L-lactic acid (PDLLA-PEG) hydrogel and then loaded it with TGF-b3 and human bone marrow-derived mesenchymal stem cells (BM-MSCs).…”