Cartilage lacuna-biomimetic hydrogel microspheres endowed with integrated biological signal boost endogenous articular cartilage regeneration  

作　　者：Hao Li Tianyuan Zhao Zhiguo Yuan Tianze Gao Yongkang Yang Runmeng Li Qinyu Tian Peifu Tang Quanyi Guo Licheng Zhang 

机构地区：[1]School of Medicine,Nankai University,Tianjin,China [2]Institute of Orthopedics,The First Medical Center,Chinese PLA General Hospital,Beijing Key Lab of Regenerative Medicine in Orthopedics,Key Laboratory of Musculoskeletal Trauma&War Injuries PLA,No.28 Fuxing Road,Haidian District,Beijing,China [3]Department of Orthopedics,The Fourth Medical Center,Chinese PLA General Hospital,Beijing,China [4]National Clinical Research Center for Orthopedics,Sports Medicine&Rehabilitation,Beijing,China [5]Department of Orthopaedics,Beijing Key Laboratory of Spinal Disease Research,Peking University Third Hospital,Beijing,China [6]Department of Bone and Joint Surgery,Renji Hospital,School of Medicine,Shanghai Jiaotong University,Shanghai,China

出　　处：《Bioactive Materials》2024年第11期61-82,共22页生物活性材料（英文）

基　　金：Beijing Natural Science Foundation(L234024);Natural Science Foundation of China(82272481,323B2043);National Key R&D Program of China(2023YFB4605800).

摘　　要：Despite numerous studies on chondrogenesis,the repair of cartilage—particularly the reconstruction of cartilage lacunae through an all-in-one advanced drug delivery system remains limited.In this study,we developed a cartilage lacuna-like hydrogel microsphere system endowed with integrated biological signals,enabling sequential immunomodulation and endogenous articular cartilage regeneration.We first integrated the chondrogenic growth factor transforming growth factor-β3(TGF-β3)into mesoporous silica nanoparticles(MSNs).Then,TGF-β3@MSNs and insulin-like growth factor 1(IGF-1)were encapsulated within microspheres made of polydopamine(pDA).In the final step,growth factor-loaded MSN@pDA and a chitosan(CS)hydrogel containing platelet-derived growth factor-BB(PDGF-BB)were blended to produce growth factors loaded composite microspheres(GFs@μS)using microfluidic technology.The presence of pDA reduced the initial acute inflammatory response,and the early,robust release of PDGF-BB aided in attracting endogenous stem cells.Over the subsequent weeks,the continuous release of IGF-1 and TGF-β3 amplified chondrogenesis and matrix formation.μS were incorporated into an acellular cartilage extracellular matrix(ACECM)and combined with a polydopamine-modified polycaprolactone(PCL)structure to produce a tissue-engineered scaffold that mimicked the structure of the cartilage lacunae evenly distributed in the cartilage matrix,resulting in enhanced cartilage repair and patellar cartilage protection.This research provides a strategic pathway for optimizing growth factor delivery and ensuring prolonged microenvironmental remodeling,leading to efficient articular cartilage regeneration.

关 键 词：Microfluidic technology Hydrogel microsphere IMMUNOMODULATION CHONDROGENESIS Articular cartilage regeneration 

分 类 号：R318[医药卫生—生物医学工程]