Traditional Chinese Medicine for Osteochondral Regeneration in Osteoarthritis

Osteochondral defects (OCD) are common in osteoarthritis (OA) and remain an unresolved clinical problem due to the chronic inflammation in the joint. Despite the development and testing of numerous biomaterials for osteochondral defects, the inflammatory environment has often been ignored. In order to address this underlying pathophysiology, we utilized two anti-inflammatory strategies for fabricating osteochondral tissue engineering materials. One strategy involved the use of the anti-inflammatory small molecule cinnamaldehyde (CIN) from traditional Chinese medicine, which we incorporated into a biphasic porous and degradable scaffold. The other strategy involved the use of bone marrow-derived mesenchymal stem cell (BMSC)-laden 3D-bioprinted multilayer scaffolds. In this study, we aimed to evaluate the effects of these two scaffolds on promoting osteochondral regeneration in OA-OCD animal models. The biphasic porous scaffolds (PK/PTC) were composed of poly lactic-co-glycolic acid with kartogenin for cartilage repair, and PLGA and β-calcium phosphate with CIN for subchondral bone repair. We evaluated the scaffolds using our well-established OA-OCD rabbit model. The effects of BMSC-laden scaffolds on osteochondral defect repair were investigated in a rat model of medial meniscectomy-induced OA. The biphasic scaffold PK/PTC promoted subchondral bone and cartilage regeneration, and reversed subchondral osteosclerosis caused by inflammation in the critically sized OA-OCD rabbit models after 16 weeks of implantation. BMSC-laden scaffolds facilitated chondrogenesis by promoting collagen II and suppressing interleukin 1β in osteochondral defects of the femoral trochlea after 12 weeks of implantation. Additionally, BMSC-laden scaffolds significantly improved joint function of the injured leg with respect to the ground support force, paw grip force, and walk gait parameters. These findings support the use of anti-inflammatory small molecules or BMSC-laden scaffolds to simultaneously inhibit joint inflammation and promote cartilage defect repair in OA joints.