Spatiotemporally dynamic therapy with shape-adaptive drug-gel for the improvement of tissue regeneration with ordered structure

Ya-Nan Fu; Yongsan Li; Bo Deng; Yingjie Yu; Fang Liu; Lei Wang; Guang Chen; Lei Tao; Yen Wei; Xing Wang

doi:10.1016/j.bioactmat.2021.06.015

Spatiotemporally dynamic therapy with shape-adaptive drug-gel for the improvement of tissue regeneration with ordered structure

Bioact Mater. 2021 Jun 23:8:165-176. doi: 10.1016/j.bioactmat.2021.06.015. eCollection 2022 Feb.

Authors

Ya-Nan Fu¹, Yongsan Li^{1

2}, Bo Deng³, Yingjie Yu⁴, Fang Liu³, Lei Wang¹, Guang Chen¹, Lei Tao², Yen Wei², Xing Wang¹

Affiliations

¹ Beijing Advanced Innovation Center for Soft Matter Science and Engineering, Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing, 100029, China.
² The Key Laboratory of Bioorganic Phosphorus Chemistry & Chemical Biology (Ministry of Education), Department of Chemistry, Tsinghua University, Beijing, 100084, China.
³ Department of Oncology of Integrative Chinese and Western Medicine, China-Japan Friendship Hospital, Beijing, 100029, China.
⁴ Institute of Translational Medicine, Shenzhen Second People's Hospital, The First Affiliated Hospital of Shenzhen University, Health Science Center, Shenzhen, 518035, China.

Abstract

A spatiotemporally dynamic therapy (SDT) is proposed as a powerful therapeutic modality that provides spatially dynamic responses of drug-carriers for adapting to the wound microenvironment. Herein, dynamic chitosan-poly (ethylene glycol) (CP) Schiff-base linkages are employed to perform SDT by directly converting a liquid drug Kangfuxin (KFX) into a gel formation. The obtained KFX-CP drug-gel with shape-adaptive property is used to treat a representative oral mucositis (OM) model in a spatiotemporally dynamic manner. The KFX-CP drug-gel creates an instructive microenvironment to regulate signaling biomolecules and endogenous cells behavior, thereby promoting OM healing by the rule of dynamically adjusting shape to fit the irregular OM regions first, and then provides space for tissue regeneration, over KFX potion control and the general hydrogel group of CP hydrogel and KFX-F127. Most interestingly, the regenerated tissue has ordered structure like healthy tissue. Therefore, the SDT provides a new approach for the design of next generation of wound dressing and tissue engineering materials.

Keywords: Drug-gel; Ordered structure; Shape-adaptive; Spatiotemporally dynamic therapy; Tissue regeneration.