Heparin-Conjugated Fibrin Hydrogel with Chondroinductive Growth Factors and Human Synovium-Derived Mesenchymal Stem Cells for the Treatment of Articular Cartilage Defects: Evaluation of Clinical Safety

The purpose of this study was to evaluate the safety of an injectable heparin-conjugated fibrin (HCF) hydrogel containing human synovium-derived mesenchymal stem cells (SDMSCs), TGF-β1, and BMP-4 after implantation into articular cartilage defect in patients with osteoarthritis (OA). The study included 15 OA patients with a mean age of 44.2±18.0 years. The median articular cartilage defect size was 4.9±2.0 cm. HCF hydrogel, containing SDMSCs and growth factors (TGF-β1 and BMP-4), was implanted into the cartilage defect using DUPLOJECT two-syringe device connected with the DUPLOTIP dual lumen cannula. Clinical and radiological outcomes were evaluated with VAS, WOMAC, KOOS, and MOCART. The clinical study results showed that implantation of HCF hydrogel with autologous SDMSCs, TGF-β1, and BMP-4 appeared to be safe and did not show severe adverse events in OA patients. The assessment of clinical outcomes after 6 months showed improvement in VAS, WOMAC, and KOOS scores in all patients. The MOCART evaluation demonstrated an enhancement of cartilage tissue repair in 73.3% of OA patients at 6 months after surgery. Thus, implantation of HCF hydrogel with SDMSCs, TGF-β1, and BMP-4 was safe and demonstrated signs of improvement in articular cartilage repair. The evaluation of the long-term safety and therapeutic efficacy of HCF hydrogel is required in a further clinical study using a larger number of OA patients.