Affiliation:
1. Department of Orthopaedics Shanghai Jiao Tong University Affiliated Sixth People's Hospital 600 Yishan Rd Shanghai 200233 P. R. China
2. Center for Advanced Low‐dimension Materials State Key Laboratory for Modification of Chemical Fibers and Polymer Materials College of Chemistry Chemical Engineering and Biotechnology Donghua University Shanghai 201620 P. R. China
3. Shanghai Jiao Tong University School of Medicine 227 South Chongqing Rd Shanghai 200025 P. R. China
Abstract
AbstractTendon injuries, often leading to debilitating adhesions, pose significant challenges in clinical practice. Conventional treatments have limitations, necessitating novel strategies. Injectable hydrogels, known for their biocompatibility, have shown promise. To enhance their antiadhesive properties, researchers have started incorporating drugs. Existing drug delivery systems often peak in the initial days, falling short during the fibroblast proliferation phase which occurs ≈1 week after injury. In this research, CI1040 is selected as an antiadhesion drug, encapsulated within zeolitic imidazolate framework‐8(ZIF‐8), and incorporated into oxidized hyaluronic acid/N‐carboxyethyl chitosan(OHA/CEC) hydrogel(Gel), resulting in the synthesis of CI1040@ZIF@Gel. This unique pH‐responsive drug release system involves encapsulating CI1040 within ZIF‐8, a substance that degrades under acidic conditions while remaining stable in physiological environments. This system selectively releases the drug during the fibroblast proliferation phase, responding to the localized pH reduction post‐tendon injury. CI1040@ZIF@Gel exerted a 65% inhibition on extracellular signal‐regulated kinase (ERK) phosphorylation, reducing the production of collagen types III (Col III) in the adhesion area by 56%. These results indicate that CI1040@ZIF@Gel can effectively inhibit fibroblast proliferation and adhesion through the interleukin 9 receptor/mitogen‐activated protein kinase/extracellular signal‐regulated kinase(IL9r/MEK/ERK) pathway, while also acting as a physical barrier to prevent the formation of tendon adhesion.
Funder
National Natural Science Foundation of China
Shanghai Municipal Education Commission
Shanghai Municipal Health Commission
Shanghai Educational Development Foundation