Molecular recognition-directed site-specific release of stem cell differentiation inducers for enhanced joint repair

Xuemin Liu; Yunhua Chen; Angelina S Mao; Chengkai Xuan; Zhifang Wang; Huichang Gao; Geng An; Ye Zhu; Xuetao Shi; Chuanbin Mao

doi:10.1016/j.biomaterials.2019.119644

Molecular recognition-directed site-specific release of stem cell differentiation inducers for enhanced joint repair

Biomaterials. 2020 Feb:232:119644. doi: 10.1016/j.biomaterials.2019.119644. Epub 2019 Dec 6.

Authors

Xuemin Liu¹, Yunhua Chen², Angelina S Mao³, Chengkai Xuan⁴, Zhifang Wang⁵, Huichang Gao⁶, Geng An⁷, Ye Zhu⁸, Xuetao Shi⁹, Chuanbin Mao¹⁰

Affiliations

¹ School of Biomedical Science and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 510006, China; National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, China.
² School of Biomedical Science and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 510006, China.
³ Norman North High School, Norman, OK, 73069, USA.
⁴ National Engineering Research Center for Tissue Restoration and Reconstruction, South China University of Technology, Guangzhou, 510006, China.
⁵ Key Laboratory of Biomedical Engineering of Guangdong Province, South China University of Technology, Guangzhou, 510006, China.
⁶ Key Laboratory of Biomedical Materials and Engineering of the Ministry of Education, South China University of Technology, Guangzhou, 510006, China.
⁷ Department of Reproductive Medicine Third Affiliated Hospital of Guangzhou Medical University Guangzhou, 510150, China.
⁸ Department of Chemistry & Biochemistry, Stephenson Life Science Research Center, University of Oklahoma, 101 Stephenson Parkway, Norman, OK, 73019, USA.
⁹ School of Biomedical Science and Engineering, South China University of Technology, Guangzhou International Campus, Guangzhou, 510006, China; Norman North High School, Norman, OK, 73069, USA; China Guangzhou Regenerative Medicine and Health Guangdong Laboratory, Guangzhou, 510005, China. Electronic address: [email protected].
¹⁰ Department of Chemistry & Biochemistry, Stephenson Life Science Research Center, University of Oklahoma, 101 Stephenson Parkway, Norman, OK, 73019, USA. Electronic address: [email protected].

PMID: 31884017
DOI: 10.1016/j.biomaterials.2019.119644

Abstract

The remarkable difference in cell type and matrix composition between two connected parts of a joint (cartilage and subchondral bone) makes it challenging to simultaneously regenerate both parts for joint repair. Thus we chemically designed a biphasic hydrogel made of two well-bonded shape-tunable hydrogel phases, termed bone-regenerating hydrogel (BRH) and cartilage-regenerating hydrogel (CRH). The BRH and CRH, encapsulating stem cells, were produced by photo-crosslinking bone and cartilage matrix-mimicking biopolymers and a nanobox (β-cyclodextrin) in situ in the subchondral bone defect and cartilage defect, respectively. The nanoboxes in BRH and CRH were loaded with osteogenic and chondrogenic differentiation inducers (melatonin and kartogenin) by host-guest interactions, respectively. Such interactions directed the sustained phase- and defect site-specific release of the inducers and subsequent site-specific stem cell differentiation into cartilage and bone forming cells for joint repair. The strategy opens up a new chemical approach to biomaterials with phase-specific drug release for tissue repair.

Keywords: Biomimetic material; Differentiation inducer; Drug nanobox; Osteochondral regeneration; Tissue regeneration; host−guest interactions.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cartilage*
Cell Differentiation*
Chondrogenesis*
Hydrogels
Osteogenesis
Stem Cells*

Substances

Hydrogels