Modified poloxamer 407 and hyaluronic acid thermosensitive hydrogel-encapsulated keratinocyte growth factor 2 improves knee osteoarthritis in rats

Abstract

Osteoarthritis (OA) is one of the most common chronic diseases, causing degenerative changes in articular cartilage and subchondral bones. To date, there is no effective drug to delay the progression of OA in clinical practice. In this study, we synthesized and prepared a new thermosensitive hydrogel called PHA hydrogel, a mixture of normal poloxamer 407 and hyaluronic acid-modified poloxamer 407, and we investigated the effects of the PHA hydrogel loaded with keratinocyte growth factor 2 (KGF-2) on rats with papain-induced OA. First, we evaluated the safety of the PHA hydrogel in vitro and in vivo. The results showed that the PHA hydrogel had suitable osmotic pressure and no obvious cytotoxicity or adverse reactions after intra-articular injection. In addition, the PHA hydrogel improved the stability of KGF-2. Next, we studied the effects of the PHA hydrogel loaded with KGF-2 (PHA-KGF-2) on OA in rats. PHA-KGF-2 significantly improved the morphology and inflammation of the articular cartilage, reduced the loss of proteoglycan, and balanced collagen metabolism compared with KGF-2 alone. These data demonstrated that the PHA hydrogel is a safe biomaterial that can protect KGF-2, and thus is a promising therapeutic strategy for patients with OA.

Keywords

• Thermosensitive hydrogel
• Poloxamer
• Hyaluronic acid
• Keratinocyte growth factor 2
• Safety
• Osteoarthritis