Simultaneous Recruitment of Stem Cells and Chondrocytes Induced by a Functionalized Self-Assembling Peptide Hydrogel Improves Endogenous Cartilage Regeneration.

Xiao Lv,Zhe Wang,Kun Fu,Caixia Sun,Songfeng Chen,Zhidao Xia,Zengwu Shao,Qiang Wu,Binwu Hu,Baichuan Wang

doi:10.3389/fcell.2020.00864

Abstract

The goal of treating articular cartilage (AC) injury is to regenerate cartilage tissue and to integrate the neo-cartilage with surrounding host cartilage. However, most current studies tend to focus on engineering cartilage; interface integration has been somewhat neglected. An endogenous regenerative strategy that simultaneously increases the recruitment of bone marrow mesenchymal stem cells (BMSCs) and chondrocytes may improve interface integration and cartilage regeneration. In this study, a novel functionalized self-assembling peptide hydrogel (KLD-12/KLD-12-LPP, KLPP) containing link protein N-peptide (LPP) was designed to optimize cartilage repair. KLPP hydrogel was characterized using transmission electron microscopy (TEM) and rheometry. KLPP hydrogel shared a similar microstructure to KLD-12 hydrogel which possesses a nanostructure with a fiber diameter of 25–35 nm. In vitro experiments showed that KLPP hydrogel had little cytotoxicity, and significantly induced chondrocyte migration and increased BMSC migration compared to KLD-12 hydrogel. In vivo results showed that defects treated with KLPP hydrogel had higher overall International Cartilage Repair Society (ICRS) scores, Safranin-O staining scores and cumulative histology scores than untreated defects or defects treated with KLD-12 hydrogel, although defects treated with KLD-12 and KLPP hydrogels received similar type II collagen immunostaining scores. All these findings indicated that the simple injectable functionalized self-assembling peptide hydrogel KLPP facilitated simultaneous recruitment of endogenous chondrocytes and BMSCs to promote interface integration and improve cartilage regeneration, holding great potential as a one-step surgery strategy for endogenous cartilage repair.

Highlights

Articular cartilage (AC) defects commonly occur as a result of either trauma or degenerative disease
We evaluated the effect of KLPP hydrogel on the migration of chondrocytes and bone marrow mesenchymal stem cells (BMSCs) in vitro, while in vivo experiments were performed to test the ability of KLPP hydrogel to improve interface integration and cartilage regeneration in a rabbit osteochondral defect model
A hydrogel was formed when KLD-12-link protein N-peptide (LPP) peptide solution was mixed with KLD-12 peptide solution at a ratio of 1:1

Summary

Introduction

Articular cartilage (AC) defects commonly occur as a result of either trauma or degenerative disease. Many exogenous cell-based methods have been used to repair and regenerate damaged AC in both experimental models and clinical patients, and acceptable outcomes have been obtained (Nixon et al, 2017; McIntyre et al, 2018; Otto et al, 2018). These methods are usually associated with complicated procedures, donor-site morbidities and less controllable regulation during ex vivo cell expansion (Malda et al, 2003; Saei et al, 2017; Ozucer et al, 2018). An endogenous regenerative strategy that simultaneously increases recruitment of stem cells and chondrocytes may promote interface integration and improve cartilage regeneration

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