title: Chitosan microspheres with an extracellular matrix-mimicking nanofibrous structure as cell-carrier building blocks for bottom-up cartilage tissue engineering.
abstract: Scaffolds for tissue engineering (TE) which closely mimic the physicochemical properties of the natural extracellular matrix (ECM) have been proven to advantageously favor cell attachment, proliferation, migration and new tissue formation. Recently, as a valuable alternative, a bottom-up TE approach utilizing cell-loaded micrometer-scale modular components as building blocks to reconstruct a new tissue in vitro or in vivo has been proved to demonstrate a number of desirable advantages compared with the traditional bulk scaffold based top-down TE approach. Nevertheless, micro-components with an ECM-mimicking nanofibrous structure are still very scarce and highly desirable. Chitosan (CS), an accessible natural polymer, has demonstrated appealing intrinsic properties and promising application potential for TE, especially the cartilage tissue regeneration. According to this background, we report here the fabrication of chitosan microspheres with an ECM-mimicking nanofibrous structure for the first time based on a physical gelation process. By combining this physical fabrication procedure with microfluidic technology, uniform CS microspheres (CMS) with controlled nanofibrous microstructure and tunable sizes can be facilely obtained. Especially, no potentially toxic or denaturizing chemical crosslinking agent was introduced into the products. Notably, in vitro chondrocyte culture tests revealed that enhanced cell attachment and proliferation were realized, and a macroscopic 3D geometrically shaped cartilage-like composite can be easily constructed with the nanofibrous CMS (NCMS) and chondrocytes, which demonstrate significant application potential of NCMS as the bottom-up cell-carrier components for cartilage tissue engineering.
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, P. R. China. zhzhy639@163.com.
authors.forename: Yong
authors.initials: Y
authors.lastname: Zhou
authors.affiliation: Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China. shyu@ustc.edu.cn.
authors.forename: Huai-Ling
authors.initials: HL
authors.lastname: Gao
authors.affiliation: Department of Dental Implant Center, Stomatologic Hospital & College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei 230032, P. R. China. zouduohongyy@126.com.
authors.forename: Li-Li
authors.initials: LL
authors.lastname: Shen
authors.affiliation: Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China. shyu@ustc.edu.cn.
authors.forename: Zhao
authors.initials: Z
authors.lastname: Pan
authors.affiliation: Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China. shyu@ustc.edu.cn.
authors.forename: Li-Bo
authors.initials: LB
authors.lastname: Mao
authors.affiliation: Department of Dental Implant Center, Stomatologic Hospital & College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei 230032, P. R. China. zouduohongyy@126.com.
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.affiliation: Department of Dental Implant Center, Stomatologic Hospital & College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei 230032, P. R. China. zouduohongyy@126.com.
authors.forename: Jia-Cai
authors.initials: JC
authors.lastname: He
authors.affiliation: Department of Dental Implant Center, Stomatologic Hospital & College, Key Laboratory of Oral Diseases Research of Anhui Province, Anhui Medical University, Hefei 230032, P. R. China. zouduohongyy@126.com.
authors.forename: Duo-Hong
authors.initials: DH
authors.lastname: Zou
authors.affiliation: Department of Oral and Maxillofacial Surgery, Ninth People's Hospital, School of Stomatology, Shanghai Jiao Tong University, Shanghai 200011, P. R. China. zhzhy639@163.com.
authors.forename: Zhi-Yuan
authors.initials: ZY
authors.lastname: Zhang
authors.affiliation: Division of Nanomaterials & Chemistry, Hefei National Laboratory for Physical Sciences at Microscale, Department of Chemistry, University of Science and Technology of China, Hefei, Anhui 230026, P. R. China. shyu@ustc.edu.cn.
authors.forename: Shu-Hong
authors.initials: SH
authors.lastname: Yu
mesh_terms: D000818:Animals; D002356:Cartilage; D002478:Cells, Cultured; D048271:Chitosan / Q000737:chemistry*; D019902:Chondrocytes / Q000166:cytology / Q000378:metabolism*; D005109:Extracellular Matrix / Q000737:chemistry*; D008863:Microspheres; D057139:Nanofibers / Q000737:chemistry*; D011817:Rabbits; D023822:Tissue Engineering
chemical_list: D048271:Chitosan