Feasibility of a self‐assembling peptide hydrogel scaffold for meniscal defect: An in vivo study in a rabbit model

Abstract

The inner avascular zone of the meniscus has limited healing capacity as the area is poorly vascularized. Although peptide hydrogels have been reported to regenerate bone and cartilage, their effect on meniscus regeneration remains unknown. We tested whether the self-assembling peptide hydrogel scaffold KI24RGDS stays in the meniscal lesion and facilitates meniscal repair and regeneration in an induced rabbit meniscal defect model. Full-thickness (2.0 mm diameter) cylindrical defects were introduced into the inner avascular zones of the anterior portions of the medial menisci of rabbit knees (n = 40). Right knee defects were left empty (control group) while the left knee defects were transplanted with peptide hydrogel (KI24RGDS group). Macroscopic meniscus scores were significantly higher in the KI24RGDS group than in the control group at 2, 4, and 8 weeks after surgery. Histological examinations including quantitative and qualitative scores indicated that compared with the control group, the reparative tissue in the meniscus was significantly enhanced in the KI24RGDS group at 2, 4, 8, and 12 weeks after surgery. Immunohistochemical staining showed that the reparative tissue induced by KI24RGDS at 12 weeks postimplantation was positive for Type I and II collagen. KI24RGDS is highly biocompatible and biodegradable, with strong stiffness, and a three dimensional structure mimicking native extracellular matrix and RGDS sequences that enhance cell adhesion and proliferation. This in vivo study demonstrated that KI24RGDS remained in the meniscal lesion and facilitated the repair and regeneration in a rabbit meniscal defect model.

Structural and photoactive properties of self-assembled peptide-based nanostructures and their optical bioapplication in food analysis

“…They can also be obtained via the self-assembly of small molecules. Peptide molecules with the ability to self-assemble into physically cross-linked fibre-like structures are ideal alternatives [60] , [61] . Peptide self-assembled hydrogels have outstanding advantages, such that they are biocompatible, biodegradable, and nontoxic [62] .…”

Peptide-Based Hydrogels: New Materials for Biosensing and Biomedical Applications

“…RGD peptides improved growth of cells, while the anti-VEGF-R2 DNA aptamer seemed to promote cell viability, and also angiogenesis by tube formation by endothelial cells, useful for advanced wound healing applications. Okuno et al tested the potential applications of a hydrogel scaffold KI24RGDS to facilitate meniscal regeneration in an induced rabbit meniscal defect model [ 154 ]. They reported a high biocompatibility of the KI24RGDS hydrogel with strong stiffness, possessing a similar native extracellular matrix useful for cell adhesion and proliferation.…”

Applications and prospects of different functional hydrogels in meniscus repair

“…The aforementioned studies indicate that different regions of the meniscus release different factors and substances that stimulate cells to differentiate into cells with different functions, but more research is needed to reveal the underlying mechanisms. Okuno et al reported that KI24RGDS peptide hydrogel facilitated meniscus repair in a rabbit meniscal defect model ( Okuno et al, 2021 ). In vitro and in vivo studies by Forriol et al and Ozeki et al demonstrated that bone morphogenetic protein-7 (BMP-7) is a suitable growth factor to stimulate meniscus regeneration and delay cartilage degeneration ( Ozeki et al, 2013 ; Forriol et al, 2014 ).…”

“…Self-assembled polypeptide hydrogels are normally stable and can aggregate spontaneously by forming non-covalent bonds between polypeptide molecules, such as hydrogen bonds, electrostatic interactions, and π-π stacking interactions. Okuno et al demonstrated that a self-assembling peptide hydrogel scaffold presented a repair and regeneration effect in the meniscus defect of a rabbit model ( Okuno et al, 2021 ).…”

“…When applied to an orthotopic model of meniscal injury in SD rat, mECM is superior than collagen I scaffold in reduction of osteophyte formation and prevention of joint space narrowing and osteoarthritis development as evidenced by histology and micro-CT analysis Zhong et al (2020)Chemokines (platelet-derived growth factor-BB, PDGF-BB) and small chondroinductive molecules (kartogenin, KGN)Polycaprolactone hydrogelThe scaffold morphology, drug release and the effects of releasing the drugs in a sequentially controlled manner from the composite scaffolds on the fate of MSCs were evaluated, and the healing effect of the hydrogel was assessed in a rabbit model established with a critical-size medial meniscectomy in vivoThe meniscal scaffolds containing both drugs had combinational advantages in enhancing cell migration and synergistically promoted MSC chondrogenic differentiation. The dual drugloaded scaffolds also significantly promoted in vivo neomeniscal regeneration three and 6 months after implantation in terms of histological and immunological phenotypesHao et al (2021) Peptide KI24RGDS peptide hydrogel Full-thickness (2.0 mm diameter) cylindrical defects were introduced into the inner avascular zones of the anterior portions of the medial menisci of rabbit knees in vivo KI24RGDS remained in the meniscal lesion and facilitated the repair and regeneration in a rabbit meniscal defect modelOkuno et al (2021)…”