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The combined effects of continuous passive motion treatment and acellular PLGA implants on osteochondral regeneration in the rabbit
Nai-Jen Chang a, Chih-Chan Lin b, Chien-Feng Li c, Dong-An Wang d, Nontapot Issariyaku a, Ming-Long Yeha,e,*a Institute of Biomedical Engineering, National Cheng Kung University, Taiwan
b Laboratory Animal Center, Department of Medical Research, Chi-Mei Medical Center, Taiwan
c Division of Clinical Pathology, Department of Pathology, Chi-Mei Medical Center, Taiwan
d Division of Bioengineering and Biomedical Engineering, Nanyang Technological University, Singapore
e Medical Device Innovation Center, National Cheng Kung University, Taiwan
 We investigated the active role of clinical rehabilitation in osteochondral regeneration using continuous passive motion (CPM) treatment together with acellular PLGA implants. CPM treatment was performed and compared with immobilization (Imm) treatment and intermittent active motion (IAM) treatment upon full-thickness osteochondral defects either with or without an PLGA implant in the PI (PLGAimplanted) and ED (empty defect) models. The PI and ED tests were performed in 38 rabbits for 4 and 12 weeks. At the end of testing, the PI-CPM group had the best regeneration with nearly normal articular surfaces and no joint contracture or inflammatory reaction. In contrast, degenerated joints, abrasion cartilage surfaces and synovitis were observed in the Imm and IAM groups. The achieved bone volume/ tissue volume (BV/TV) ratio, which was measured using micro-CT, was significantly higher in the CPM group compared with the Imm and IAM groups; in particular, the performance of the PI-CPM group exceeds that of the ED-CPM group. The thickness of the trabecular (subchondral) bone was visibly increased in all of the groups from 4 through 12 weeks of testing. However, a histological analysis revealed differences in cartilage regeneration. At week 4, compared with the ED samples, all of the PI groups exhibited better collagen alignment and higher GAG content in the core of their repaired tissues, particularly in the PI-CPM group. At week 12, sound osteochondral repair and hyaline cartilaginous regeneration was observed in the PI-CPM group, and this was marked by type II collagen expression, osteocyte maturation, and trabecular boney deposition. In contrast, the PI-Imm and PI-IAM groups exhibited fibrocartilaginous tissues that had modest GAG content. In summary, this study demonstrates that early CPM treatment together with acellular PLGA implantation has significant positive effects on osteochondral regeneration in rabbit knee joint models.
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