Evaluation of Meniscal Regeneration in a Mini Pig Model Treated With a Novel Polyglycolic Acid Meniscal Scaffold

Otsuki, Shuhei; Nakagawa, Kosuke; Murakami, Tomohiko; Sezaki, Shunsuke; Sato, Hideki; Suzuki, Masakazu; Okuno, Nobuhiro; Wakama, Hitoshi; Kaihatsu, Kunihiro; Neo, Masashi

doi:10.1177/0363546519850578

Cited by 24 publications

(25 citation statements)

References 43 publications

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“…28 Our previous meniscus studies showed hat PGA induces cell proliferation within 4 weeks after implantation. 21,29 In the current study, cell viability assay showed that a large number of cells survived in the MSS group for 2-4 weeks. Based on these results, we expected that a two-layer scaffold consisting of PGA in contact with the meniscus surface and P(LA/CL) in contact with the cartilage surface might be a good combination.…”

Section: Discussionsupporting

confidence: 48%

Development of a novel meniscal sheet scaffold and its effectiveness for meniscal regeneration in a rabbit defect model

et al. 2021

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This study evaluated the biomechanical strength of a novel two-layer meniscal sheet scaffold (MSS) consisting of polyglycolic acid and poly-Llactic acid/caprolactone and investigated meniscal healing using wrapping treatment for meniscal defect model in a rabbit. The ultimate failure load of the MSS was determined using a tensile testing machine, in vitro. A 2-mm cylindrical defects were created at the medial meniscus of rabbit knees (n = 40). Each knee was assigned to one of two groups. The defect group was not treated and the MSS group underwent wrapping treatment with MSS. Menisci were harvested at 2, 4, 8, and 12 weeks post-implantation. The regenerated meniscus and defect size were evaluated using macrophotographs. Ishida scores for regenerated tissue were determined using Safranin-O/Fast Green staining. Immunohistochemical analysis of Ki-67 for cell proliferation, anti-type I and II collagen antibodies for structure of the regenerated tissue was elucidated. Medial femoral cartilage was stained with Safranin-O/Fast Green and evaluated with Osteoarthritis Research Society International (OARSI) scores. The strength of MSS was maintained over 90% from initial time point to 4 weeks after hydrolysis and over 60% of the strength remained at 8 weeks. The surface area of the meniscus was larger and the defect size smaller in the MSS group than in the defect group at 8 and 12 weeks. Ishida scores revealed that the MSS group improved significantly compared to that of the defect group at all postsurgery time points evaluated. Ki-67 positive cell ratio was significantly higher in the MSS group. OARSI score of the defect group was significantly higher and the defect group showed progressive degeneration in the articular cartilage from 8 to 12 weeks. Overall, wrapping meniscus defects with MSS was useful for accelerating meniscal healing from an early stage and beneficial for tissue regeneration and promoting extracellular matrix maturation.

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Section: Discussionsupporting

confidence: 48%

Development of a novel meniscal sheet scaffold and its effectiveness for meniscal regeneration in a rabbit defect model

et al. 2021

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“…The results showed that the scaffold provided appropriate initial strength and could prevent cartilage degeneration with relatively low inflammation. However, the compressive stress and elastic modulus of the scaffold were significantly inferior to those of the native meniscus ( Otsuki et al, 2019 ).…”

Section: Polymers For Meniscal Tissue Engineering Applicationsmentioning

confidence: 87%

“…As a biodegradable polymer with excellent biocompatibility and mechanical strength, poly(glycolic acid) (PGA) has been widely used in the biomechanical and medical fields since the 1970s and can serve as a scaffolding material to repair articular cartilage in clinical practice ( Siclari et al, 2018 ; Otsuki et al, 2019 ; Cojocaru et al, 2020 ). In meniscal tissue engineering, a 3D, meniscal-like, PGA-hyaluronan implant with high porosity was developed, and this scaffold showed high biocompatibility and improved the expression of chondrogenic genes during coculture with human meniscal cells in vitro .…”

Section: Polymers For Meniscal Tissue Engineering Applicationsmentioning

confidence: 99%

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

Yang

et al. 2021

Front. Cell Dev. Biol.

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Knee menisci are structurally complex components that preserve appropriate biomechanics of the knee. Meniscal tissue is susceptible to injury and cannot heal spontaneously from most pathologies, especially considering the limited regenerative capacity of the inner avascular region. Conventional clinical treatments span from conservative therapy to meniscus implantation, all with limitations. There have been advances in meniscal tissue engineering and regenerative medicine in terms of potential combinations of polymeric biomaterials, endogenous cells and stimuli, resulting in innovative strategies. Recently, polymeric scaffolds have provided researchers with a powerful instrument to rationally support the requirements for meniscal tissue regeneration, ranging from an ideal architecture to biocompatibility and bioactivity. However, multiple challenges involving the anisotropic structure, sophisticated regenerative process, and challenging healing environment of the meniscus still create barriers to clinical application. Advances in scaffold manufacturing technology, temporal regulation of molecular signaling and investigation of host immunoresponses to scaffolds in tissue engineering provide alternative strategies, and studies have shed light on this field. Accordingly, this review aims to summarize the current polymers used to fabricate meniscal scaffolds and their applications in vivo and in vitro to evaluate their potential utility in meniscal tissue engineering. Recent progress on combinations of two or more types of polymers is described, with a focus on advanced strategies associated with technologies and immune compatibility and tunability. Finally, we discuss the current challenges and future prospects for regenerating injured meniscal tissues.

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“…12 Similarly, several researchers are performing in vivo meniscus and articular cartilage repair in the minipig. [60][61][62] Here, constructs were generated from the costal cartilage of the Yucatan minipig and stimulated during the maturation stage. Similar to constructs derived from bovine articular chondrocytes, compressive stiffness and tensile strength and stiffness of minipig-derived neocartilage significantly increased by 46%, 78%, and 78%, respectively, when FIS stress was applied.…”

Section: Discussionmentioning

confidence: 99%

The functionality and translatability of neocartilage constructs are improved with the combination of fluid‐induced shear stress and bioactive factors

et al. 2022

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Neocartilage tissue engineering aims to address the shortcomings of current clinical treatments for articular cartilage indications. However, advancement is required toward neocartilage functionality (mechanical and biochemical properties) and translatability (construct size, gross morphology, passage number, cell source, and cell type). Using fluid‐induced shear (FIS) stress, a potent mechanical stimulus, over four phases, this work investigates FIS stress’ efficacy toward creating large neocartilage derived from highly passaged minipig costal chondrocytes, a species relevant to the preclinical regulatory process. In Phase I, FIS stress application timing was investigated in bovine articular chondrocytes and found to improve the aggregate modulus of neocartilage by 151% over unstimulated controls when stimulated during the maturation stage. In Phase II, FIS stress stimulation was translated from bovine articular chondrocytes to expanded minipig costal chondrocytes, yielding a 46% improvement in aggregate modulus over nonstimulated controls. In Phase III, bioactive factors were combined with FIS stress to improve the shear modulus by 115% over bioactive factor‐only controls. The translatability of neocartilage was improved in Phase IV by utilizing highly passaged cells to form constructs more than 9‐times larger in the area (11 × 17 mm), yielding an improved aggregate modulus by 134% and a flat morphology compared to free‐floating, bioactive factor‐only controls. Overall, this study represents a significant step toward generating mechanically robust, large constructs necessary for animal studies, and eventually, human clinical studies.

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Evaluation of Meniscal Regeneration in a Mini Pig Model Treated With a Novel Polyglycolic Acid Meniscal Scaffold

Cited by 24 publications

References 43 publications

Development of a novel meniscal sheet scaffold and its effectiveness for meniscal regeneration in a rabbit defect model

Development of a novel meniscal sheet scaffold and its effectiveness for meniscal regeneration in a rabbit defect model

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

The functionality and translatability of neocartilage constructs are improved with the combination of fluid‐induced shear stress and bioactive factors

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