Inflammation-Responsive Functional Core-Shell Micro-Hydrogels Promote Rotator Cuff Tendon-To-Bone Healing by Recruiting MSCs and Immuno-Modulating Macrophages in Rats

被引：1

作者：

Chen, Baojun ^{[1
]}

Zhao, Xin ^{[2
,3
,4
]}

Xu, Meiguang ^{[5
]}

Luo, Jinlong ^{[2
,3
,4
]}

Bai, Lang ^{[5
]}

Han, Qian ^{[5
]}

Gao, Yanzheng ^{[1
]}

Guo, Baolin ^{[2
,3
,4
]}

Yin, Zhanhai ^{[5
]}

机构：

[1] Zhengzhou Univ, Henan Prov Peoples Hosp, Dept Surg Spine & Spinal Cord, Henan Prov Intelligent orthoped technol innovat &, Zhengzhou 450003, Peoples R China

[2] Xi An Jiao Tong Univ, Frontier Inst Sci & Technol, Coll Stomatol, Xian 710049, Peoples R China

[3] Xi An Jiao Tong Univ, Coll Stomatol, State Key Lab Mech Behav Mat, Xian 710049, Peoples R China

[4] Xi An Jiao Tong Univ, Coll Stomatol, Key Lab Shaanxi Prov Craniofacial Precis Med Res, Xian 710049, Peoples R China

[5] Xi An Jiao Tong Univ, Dept Orthopaed, Affiliated Hosp 1, Xian 710061, Peoples R China

来源：

ADVANCED HEALTHCARE MATERIALS | 2025年 / 14卷 / 02期

基金：

中国国家自然科学基金; 中国博士后科学基金;

关键词：

core-shell micro-hydrogel; inflammation-responsive; M2; macrophage; sustained release; tendon-to-bone healing; MESENCHYMAL STEM-CELLS; CARTILAGE REPAIR; POLARIZATION; COLLAGEN; ACTIVATION; MANAGEMENT; INTEGRITY; RELEASE; GRAFT; ACID;

D O I：

10.1002/adhm.202404091

中图分类号：

R318 [生物医学工程];

学科分类号：

0831 ;

摘要：

Rotator cuff injuries often necessitate surgical intervention, but the outcomes are often unsatisfactory. The underlying reasons can be attributed to multiple factors, with the intricate inflammatory activities and insufficient presence of stem cells being particularly significant. In this study, an innovative inflammation-responsive core-shell micro-hydrogel is designed for independent release of SDF-1 and IL-4 within a single delivery system to promote tendon-to-bone healing by recruiting MSCs and modulating M2 macrophages polarization. First, a MMP-2 responsive hydrogel loaded with IL-4 (GelMA-MMP/IL-4) is synthesized by cross-linking gelatin methacrylate (GelMA) with MMP-2 substrate peptide. Then, the resulting core particles are coated with a shell of chitosan /SDF-1/hyaluronic acid (CS/HA/SDF-1) using the layer-by-layer electrostatic deposition method to form a core-shell micro-hydrogel composite. The core-shell micro-hydrogel shows sustained release of SDF-1 and MMP-2-responsive release of IL-4 associated in situ MSCs homing and smart inflammation regulation by promoting M2 macrophages polarization. Additionally, by injecting these micro-hydrogels into a rat rotator cuff tear and repair model, notable improvements of fibrocartilage layer are observed between tendon and bone. Notably, this study presents a new and potentially powerful environment-responsive drug delivery strategy that offers valuable insights for regulating the intricate micro-environment associated with tissue regeneration.

引用

页数：17