Therapeutic effects of intra‐articular ultra‐purified low endotoxin alginate administration on an experimental canine osteoarthritis model

Tsukuda, Yoko; Onodera, Tomohiro; Itô, Masayuki; Izumisawa, Yasuharu; Kasahara, Yasuhiko; Igarashi, Tatsuya; Ohzawa, Nobuo; Todoh, Masahiro; Tadano, Shigeru; Iwasaki, Norimasa

doi:10.1002/jbm.a.35490

Cited by 13 publications

(10 citation statements)

References 32 publications

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“…17 The low endotoxin level allows safe clinical application of the UPAL gel by preventing immunologic reactions to the implanted material. 24,37 The UPAL gel can instantaneously gelate in situ and enhance the cellular proliferation and chondrogenic differentiation of bone marrow–derived mesenchymal stem cells, resulting in better reparative tissues in rabbit and canine osteochondral defects. 7,8,17,34 In addition, the chemokine contained in this material enhances the recruitment of bone marrow–derived mesenchymal stem cells and successfully achieves hyaline-like cartilage repair without exogenous cellular transplantation.…”

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confidence: 99%

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

et al. 2018

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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.

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

et al. 2018

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“…Thus, we used UPAL ® gel to administer CCL21 to adult injury sites. Alginate acid is known to exert a cartilage differentiation effect, and UPAL ® gel has reduced endotoxin levels and is suitable for use in vivo 11,27–30 . In addition, alginate has been widely used as a scaffold biomolecule in combination with drugs, peptides and proteins.…”

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confidence: 99%

CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults

Joutoku

Onodera

Matsuoka

et al. 2019

Sci Rep

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Juvenile tissue healing is capable of extensive scarless healing that is distinct from the scar-forming process of the adult healing response. Although many growth factors can be found in the juvenile healing process, the molecular mechanisms of juvenile tissue healing are poorly understood. Here we show that juvenile mice deficient in the chemokine receptor CCR7 exhibit diminished large-scale healing potential, whereas CCR7-depleted adult mice undergo normal scar-forming healing similar to wild type mice. In addition, the CCR7 ligand CCL21 was transiently expressed around damaged cartilage in juvenile mice, whereas it is rarely expressed in adults. Notably, exogenous CCL21 administration to adults decreased scar-forming healing and enhanced hyaline-cartilage repair in rabbit osteochondral defects. Our data indicate that the CCL21/CCR7 axis may play a role in the molecular control mechanism of juvenile cartilage repair, raising the possibility that agents modulating the production of CCL21 in vivo can improve the quality of cartilage repair in adults. Such a strategy may prevent post-traumatic arthritis by mimicking the self-repair in juvenile individuals.

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“…Previous studies with rabbit and canine models demonstrated that the intra-articular administration of ultrapurified low endotoxin alginate inhibited the progression of osteoarthritic changes. 15,32 In the current model, the implanted UPAL gel was considered to play roles in not only enhancing cartilage repair of the defect site but also protecting against degenerative changes of the implanted graft. One can reasonably conclude that these effects of UPAL gel enhance the repair of the entire osteochondral lesion treated with OAT alone.…”

Section: Discussionmentioning

confidence: 99%

Osteochondral Autograft Transplantation Technique Augmented by an Ultrapurified Alginate Gel Enhances Osteochondral Repair in a Rabbit Model

et al. 2019

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Background: One of the most important limitations of osteochondral autograft transplantation (OAT) is the adverse effect on donor sites in the knee. To decrease the number and/or size of osteochondral defects, we devised a method with biomaterial implantation after OAT. Hypothesis: OAT augmented by ultrapurified alginate (UPAL) gel enhances cartilage repair capacity. Study Design: Controlled laboratory study. Methods: Seventy-five osteochondral defects in rabbits were divided into 3 groups: osteochondral defects with OAT alone, defects with OAT augmented by UPAL gel (combined group), and defects without intervention as controls. Macroscopic and histological evaluations of the reparative tissues were performed at 4 and 12 weeks postoperatively. Histological evaluation of graft cartilage degradation was also performed. To evaluate the effects of UPAL gel on graft healing, repaired bone volumes and osseointegration of the graft were evaluated. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were also evaluated qualitatively. Results: The macroscopic and histological evaluations of the combined group were significantly superior to the other groups at 12 weeks postoperatively. Regarding degenerative change of the graft, the histological scores of the combined group were significantly higher than those of the OAT-alone group. The values of repaired subchondral bone volumes and osseointegration of the graft were almost identical in both groups. Collagen orientation and the mechanical properties of the reparative tissue and graft cartilage were significantly better in the combined group than in the other groups. Conclusion: Administration of UPAL gel in OAT enhanced cartilage repair and protected graft cartilage without inhibiting subchondral bone repair and graft survival. Clinical Relevance: OAT augmented by UPAL gel decreases the number and/or size of osteochondral grafts, minimizing the risk of donor site morbidity. This combination technique has the potential to improve clinical outcomes and expand the surgical indications for OAT.

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Therapeutic effects of intra‐articular ultra‐purified low endotoxin alginate administration on an experimental canine osteoarthritis model

Abstract: Intra-articular administration of UPLE-alginate in the early stage of OA slowed disease progression in canines. UPLE-alginate may have potential as a therapeutic agent for OA patients and reduce the number of patients who need to undergo total joint arthroplasty.

Cited by 13 publications

References 32 publications

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

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

CCL21/CCR7 axis regulating juvenile cartilage repair can enhance cartilage healing in adults

Osteochondral Autograft Transplantation Technique Augmented by an Ultrapurified Alginate Gel Enhances Osteochondral Repair in a Rabbit Model

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