Gelatin-based composite hydrogels with biomimetic lubrication and sustained drug release

Wenguo Cui,Jing Luo,Lianfu Deng,Kuan Zhang,Hongyu Zhang,Yi Wang,Xiangyang Xu,Jing Liang,Jielai Yang,Yulong Sun,Bo Wang

doi:10.1007/s40544-020-0437-5

Abstract

The occurrence of osteoarthritis is closely related to progressive and irreversible destruction of the articular cartilage, which increases the friction significantly and causes further inflammation of the joint. Thus, a scaffold for articular cartilage defects should be developed via lubrication restoration and drug intervention. In this study, we successfully synthesized gelatin-based composite hydrogels, namely GelMA-PAM-PMPC, with the properties of biomimetic lubrication and sustained drug release by photopolymerization of methacrylic anhydride modified gelatin (GelMA), acrylamide (AM), and 2-methacryloyloxyethyl phosphorylcholine (MPC). Tribological test showed that the composite hydrogels remarkably enhanced lubrication due to the hydration lubrication mechanism, where a tenacious hydration shell was formed around the zwitterionic phosphocholine headgroups. In addition, drug release test indicated that the composite hydrogels efficiently encapsulated an anti-inflammatory drug (diclofenac sodium) and achieved sustained release. Furthermore, the in vitro test revealed that the composite hydrogels were biocompatible, and the mRNA expression of both anabolic and catabolic genes of the articular cartilage was suitably regulated. This indicated that the composite hydrogels could effectively protect chondrocytes from inflammatory cytokine-induced degeneration. In summary, the composite hydrogels that provide biomimetic hydration lubrication and sustained local drug release represent a promising scaffold for cartilage defects in the treatment of osteoarthritis.

Highlights

From a biotribological viewpoint, osteoarthritis has been accepted as a lubrication deficiency-induced joint disease that is characterized by the breakdown of articular cartilage and inflammation of the joint
We successfully developed gelatin-based composite hydrogels with the properties of biomimetic lubrication and sustained local drug release (GelMA–PAM– Poly(2-methacryloyloxyethyl phosphorylcholine) (PMPC)) that could function as a cartilage substitutional scaffold for treating osteoarthritis
To evaluate the potential clinical application of the composite hydrogels, we investigated the in vitro cytotoxicity of GelMA and GelMA–PAM–PMPC on primary mouse chondrocytes and performed tests to determine whether GelMA and GelMA–PAM–PMPC can protect against chondrocyte degeneration

Summary

Introduction

Osteoarthritis has been accepted as a lubrication deficiency-induced joint disease that is characterized by the breakdown of articular cartilage and inflammation of the joint. The design of a scaffold to simultaneously achieve enhanced lubrication and sustained drug. Hydrogels have been widely studied as an ideal substitute for articular cartilage and as a drug carrier. Great effort has been devoted to designing functional hydrogels with good biocompatibility [5], high mechanical strength [6], and low coefficient of friction (COF) [7, 8]. The side chains of gelatin are rich in reactive groups (–COOH and –NH2), and different gelatin hydrogels (GelMA) have been synthesized to repair skin, bone, and articular cartilage [15, 16], in which methacrylic anhydride is introduced to initiate photopolymerization [17, 18]. To the best of our knowledge, the lubrication properties of GelMA hydrogels have rarely been investigated

Methods

Results

Conclusion