Dynamical release nanospheres containing cell growth factor from biopolymer hydrogel via reversible covalent conjugation

• Published in: Journal of biomaterials science. Polymer ed. Vol. 29; no. 11; pp. 1344 - 1359
• Main Authors: Ren, Bowen, Chen, Xueyun, Ma, Ye, Du, Shoukang, Qian, Saibo, Xu, Yongjie, Yan, Zhilin, Li, Jianliang, Jia, Yang, Tan, Huaping, Ling, Zhonghua, Chen, Yong, Hu, Xiaohong
• Format: Journal Article
• Language: English
• Published: England Taylor & Francis Ltd 01.08.2018
• Subjects: Adipose Tissue - chemistry; Biopolymers - chemistry; Boronic Acids - chemistry; Cell Proliferation - drug effects; Cell Survival - drug effects; Cross-Linking Reagents - chemistry; Drug Carriers - chemistry; Drug Compounding - methods; Drug Liberation; Glucose; Glucose - chemistry; Humans; Hydrogels; Hydrogels - chemistry; Insulin-Like Growth Factor I - pharmacology; Insulin-like growth factors; Kinetics; Maltose - chemistry; Mesenchymal Stem Cells; Nanospheres - chemistry; Particle Size; Surface Properties; Tissue engineering; Tissue Engineering - methods; Tissue Scaffolds - chemistry; tissue engineering; drug delivery; hydrogel; nanospheres; Biopolymer
• ISSN: 0920-5063; 1568-5624
• DOI: 10.1080/09205063.2018.1460140

For practical adipose regeneration, the challenge is to dynamically deliver the key adipogenic insulin-like growth factors in hydrogels to induce adipogenesis. In order to achieve dynamic release, smart hydrogels to sense the change in the blood glucose concentration is required when glucose concentration increases. In this study, a heparin-based hydrogel has been developed for use in dynamic delivery of heparin nanospheres containing insulin-like growth factor. The gel scaffold was facilely prepared in physiological conditions by the formation of boronate-maltose ester cross-links between boronate and maltose groups of heparin derivatives. Due to its intrinsic glucose-sensitivity, the exposure of gel scaffold to glucose induces maltose functionalized nanospheres dissociation off hydrogel network and thereby could dynamically move into the microenvironment. The potential of the hydrogel as a cell scaffold was demonstrated by encapsulation of human adipose-derived stem cells (ASCs) within the gel matrix in vitro. Cell culture showed that this dynamic hydrogel could support survival and proliferation of ASCs. This biocompatible coupling chemistry has the advantage that it introduces no potentially cytotoxic groups into injectable gel scaffolds formed and can create a more biomimetic microenvironment for drug and cell delivery, rendering them more suitable for potential in vivo biomedical applications. All these results indicate that this biocompatible gel scaffold can render the formulation of a therapeutically effective platform for diabetes treatment and adipose regeneration.