Continuous Passive Motion Promotes and Maintains Chondrogenesis in Autologous Endothelial Progenitor Cell-Loaded Porous PLGA Scaffolds during Osteochondral Defect Repair in a Rabbit Model.

Hsueh-Chun Wang,Horng-Chaung Hsu,Nai-Jen Chang,Tzu-Hsiang Lin,Ming-Long Yeh

doi:10.3390/ijms20020259

Abstract

Continuous passive motion (CPM) is widely used after total knee replacement. In this study, we investigated the effect of CPM combined with cell-based construct-transplantation in osteochondral tissue engineering. We created osteochondral defects (3 mm in diameter and 3 mm in depth) in the medial femoral condyle of 36 knees and randomized them into three groups: ED (empty defect), EPC/PLGA (endothelial progenitor cells (EPCs) seeded in the poly lactic-co-glycolic acid (PLGA) scaffold), or EPC/PLGA/CPM (EPC/PLGA scaffold complemented with CPM starting one day after transplantation). We investigated the effects of CPM and the EPC/PLGA constructs on tissue restoration in weight-bearing sites by histological observation and micro-computed tomography (micro-CT) evaluation 4 and 12 weeks after implantation. After CPM, the EPC/PLGA construct exhibited early osteochondral regeneration and prevention of subchondral bone overgrowth and cartilage degeneration. CPM did not alter the microenvironment created by the construct; it up-regulated the expression of the extracellular matrix components (glycosaminoglycan and collagen), down-regulated bone formation, and induced the biosynthesis of lubricin, which appeared in the EPC/PLGA/CPM group after 12 weeks. CPM can provide promoting signals during osteochondral tissue engineering and achieve a synergistic effect when combined with EPC/PLGA transplantation, so it should be considered a non-invasive treatment to be adopted in clinical practices.

Highlights

Osteochondral tissue is heterogeneous, consisting of smooth cartilage that lines the articulating surface and underlying subchondral bone
We demonstrated that a combination of early Continuous passive motion (CPM) and acellular poly lactic-co-glycolic acid (PLGA) implantation induces significant hyaline cartilage regeneration and trabecular boney deposition when compared to immobilization and intermittent active motion treatments during osteochondral regeneration in a rabbit knee joint model [25]
The porous PLGA scaffolds fabricated in this study were 3 mm in diameter and 3 mm in height as shown in (Figure 1a), the inner porous structure, interconnectivity, and honeycomb-like structures were observed by scanning electron microscopy (Figure 1b–d)

Summary

Introduction

Osteochondral tissue is heterogeneous, consisting of smooth cartilage that lines the articulating surface and underlying subchondral bone. This complexity impedes the tissue restoration after an injury to the joint or a disease. Current clinical treatments for osteochondral defects include microfracture surgery, autologous chondrocyte implantation (ACI), and osteochondral transplantation (OCT). They present problems such as an inability to produce hyaline cartilage, poor integration with the surrounding cartilage, and gradual deterioration of the repaired tissue. In MACI, a two-step surgery is necessary first to obtain the chondrocytes and to complete the implantation procedure

Methods

Results

Discussion

Conclusion