A Biomimetic Biphasic Scaffold Consisting of Decellularized Cartilage and Decalcified Bone Matrixes for Osteochondral Defect Repair.

Runfeng Cao,Anqi Zhan,Chang Chen,Depeng Meng,Kaiyan Xiao,Huitang Xia,Cheng Wang,Zheng Ci,Yong Xu,Yunlang She,Li Shen

doi:10.3389/fcell.2021.639006

Abstract

It is challenging to develop a biphasic scaffold with biomimetic compositional, structural, and functional properties to achieve concomitant repair of both superficial cartilage and subchondral bone in osteochondral defects (OCDs). This study developed a biomimsubchondraletic biphasic scaffold for OCD repair via an iterative layered lyophilization technique that controlled the composition, substrate stiffness, and pore size in each phase of the scaffold. The biphasic scaffold consisted of a superficial decellularized cartilage matrix (DCM) and underlying decalcified bone matrix (DBM) with distinct but seamlessly integrated phases that mimicked the composition and structure of osteochondral tissue, in which the DCM phase had relative low stiffness and small pores (approximately 134 μm) and the DBM phase had relative higher stiffness and larger pores (approximately 336 μm). In vitro results indicated that the biphasic scaffold was biocompatible for bone morrow stem cells (BMSCs) adhesion and proliferation, and the superficial DCM phase promoted chondrogenic differentiation of BMSCs, as indicated by the up-regulation of cartilage-specific gene expression (ACAN, Collagen II, and SOX9) and sGAG secretion; whereas the DBM phase was inducive for osteogenic differentiation of BMSCs, as indicated by the up-regulation of bone-specific gene expression (Collagen I, OCN, and RUNX2) and ALP deposition. Furthermore, compared with the untreated control group, the biphasic scaffold significantly enhanced concomitant repair of superficial cartilage and underlying subchondral bone in a rabbit OCD model, as evidenced by the ICRS macroscopic and O’Driscoll histological assessments. Our results demonstrate that the biomimetic biphasic scaffold has a good osteochondral repair effect.

Highlights

Osteochondral defects (OCDs) are a frequently occurring illness characterized by the concurrent injury of articular cartilage and subchondral bone tissue (Qiao et al, 2021)
Considering that the osteochondral structure has two distinct phases, we employed an iterative layered lyophilization technique to prepare a biomimetic and biphasic decellularized cartilage matrix (DCM)/decalcified bone matrix (DBM) scaffold with two different substrates to simulate the biphasic composition of natural osteochondral tissue
We successfully prepared the biomimetic biphasic scaffold in a cost-effectiveness method, considering the underlying DBM scaffold comes from the cancellous bone, the pore size and stiffness is hard to be modulated (Liese et al, 2013; Man et al, 2016)

Summary

Introduction

Osteochondral defects (OCDs) are a frequently occurring illness characterized by the concurrent injury of articular cartilage and subchondral bone tissue (Qiao et al, 2021). Osteochondral autograft transplantations and decellularized osteochondral grafts are employed to treat OCDs (Richter et al, 2016; Wang et al, 2018). Osteochondral autograft transplantations have insufficient sources and donor site mobility (Sherman et al, 2017). Decellularized osteochondral grafts overcome the disadvantage of an insufficient source, there are still several limitations, such as poor integration between grafts and the surrounding normal tissue, and the compact cartilage layer severely restricting tissue remodeling, which greatly hamper their clinical outcomes (Farr et al, 2016). An efficient therapeutic strategy is needed to treat OCD by restoring the intrinsic superficial cartilage and underlying bone in natural osteochondral tissue. Emerging tissue engineering strategies have provided such treatments with significant advantages compared with these traditional clinical treatments (Hu et al, 2020; Zhang et al, 2020)

Methods

Results

Conclusion