Dynamic and Cell-Infiltratable Hydrogels as Injectable Carrier of Therapeutic Cells and Drugs for Treating Challenging Bone Defects
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AbstractBiopolymeric hydrogels have been widely used as carriers of therapeutic cells and drugs for biomedical applications. However, most conventional hydrogels cannot be injected after gelation and do not support the infiltration of cells because of the static nature of their network structure. Here, we develop unique cell-infiltratable and injectable (Ci-I) gelatin hydrogels, which are physically cross-linked by weak and highly dynamic host−guest complexations and are further reinforced by limited chemical cross-linking for enhanced stability, and then demonstrate the outstanding properties of these Ci-I gelatin hydrogels. The highly dynamic network of Ci-I hydrogels allows injection of prefabricated hydrogels with encapsulated cells and drugs, thereby simplifying administration during surgery. Furthermore, the reversible nature of the weak host−guest cross-links enables infiltration and migration of external cells into Ci-I gelatin hydrogels, thereby promoting the participation of endogenous cells in the healing process. Our findings show that Ci-I hydrogels can mediate sustained delivery of small hydrophobic molecular drugs (e.g., icaritin) to boost differentiation of stem cells while avoiding the adverse effects (e.g., in treatment of bone necrosis) associated with high drug dosage. The injection of Ci-I hydrogels encapsulating mesenchymal stem cells (MSCs) and drug (icaritin) efficiently prevented the decrease in bone mineral density (BMD) and promoted in situ bone regeneration in an animal model of steroid-associated osteonecrosis (SAON) of the hip by creating the microenvironment favoring the osteogenic differentiation of MSCs, including the recruited endogenous cells. We believe that this is the first demonstration on applying injectable hydrogels as effective carriers of therapeutic cargo for treating dysfunctions in deep and enclosed anatomical sites via a minimally invasive procedure.
Acceptance Date18/10/2018
All Author(s) ListQian Feng, Jiankun Xu, Kunyu Zhang, Hao Yao, Nianye Zheng, Lizhen Zheng, Jiali Wang, Kongchang Wei, Xiufeng Xiao, Ling QIan, Liming Bian
Journal nameACS Central Science
Year2019
Month3
Volume Number5
Issue Number3
PublisherACS Publication
Place of PublicationAmerican
Pages440 - 450
ISSN2374-7951
LanguagesEnglish-United Kingdom
Keywordsinjectable hydrogel, drug delivery, stem cell, steroid-associated osteonecrosis (SAON), tissue regeneration

Last updated on 2020-31-03 at 00:16