An injectable hydrogel formed by in situ cross-linking of glycol chitosan and multi-benzaldehyde functionalized PEG analogues for cartilage tissue engineering

Author(s): Luping Cao ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Bin Cao ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Chengjiao Lu ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Guowei Wang ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Lin Yu ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵ , Jiandong Ding ¹ ^, ² ^, ³ ^, ⁴ ^, ⁵

Publication date (Electronic): 2015

Journal: Journal of Materials Chemistry B

Publisher: Royal Society of Chemistry (RSC)

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Abstract

A novel PEG analogue, poly(EO- co-Gly)-CHO, that possesses multiple aldehyde groups is designed and synthesized, and then is used as a cross-linker to react with glycol chitosan to create injectable hydrogels.

Abstract

In this study, a multi-benzaldehyde functionalized poly(ethylene glycol) analogue, poly(ethylene oxide- co-glycidol)-CHO (poly(EO- co-Gly)-CHO), was designed and synthesized for the first time, and was applied as a cross-linker to develop an injectable hydrogel system. Simply mixing two aqueous precursor solutions of glycol chitosan (GC) and poly(EO- co-Gly)-CHO led to the formation of chemically cross-linked hydrogels under physiological conditions in situ. The cross-linking was attributed to a Schiff's base reaction between amino groups of GC and aldehyde groups of poly(EO- co-Gly)-CHO. The gelation time, water uptake, mechanical properties and network morphology of the GC/poly(EO- co-Gly) hydrogels were well modulated by varying the concentration of poly(EO- co-Gly)-CHO. Degradation of the in situ formed hydrogels was confirmed both in vitro and in vivo. The integrity of the GC/poly(EO- co-Gly) hydrogels was subcutaneously maintained for up to 12 weeks in ICR mice. The feasibility of encapsulating chondrocytes in the GC/poly(EO- co-Gly) hydrogels was assessed. Live/Dead staining assay demonstrated that the chondrocytes were highly viable in the hydrogels, and no dedifferentiation of chondrocytes was observed after 2 weeks of in vitro culture. Cell counting kit-8 assay gave evidence of the remarkably sustained proliferation of the encapsulated chondrocytes. Maintenance of the chondrocyte phenotype was also confirmed with an examination of characteristic gene expression. These features suggest that GC/poly(EO- co-Gly) hydrogels hold potential as an artificial extracellular matrix for cartilage tissue engineering.

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Dror Seliktar (2012)

Hydrogels are polymeric materials distinguished by high water content and diverse physical properties. They can be engineered to resemble the extracellular environment of the body's tissues in ways that enable their use in medical implants, biosensors, and drug-delivery devices. Cell-compatible hydrogels are designed by using a strategy of coordinated control over physical properties and bioactivity to influence specific interactions with cellular systems, including spatial and temporal patterns of biochemical and biomechanical cues known to modulate cell behavior. Important new discoveries in stem cell research, cancer biology, and cellular morphogenesis have been realized with model hydrogel systems premised on these designs. Basic and clinical applications for hydrogels in cell therapy, tissue engineering, and biomedical research continue to drive design improvements using performance-based materials engineering paradigms.

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Injectable hydrogels as unique biomedical materials.

Lin Yu, Jiandong Ding (2008)

A concentrated fish soup could be gelled in the winter and re-solled upon heating. In contrast, some synthetic copolymers exhibit an inverse sol-gel transition with spontaneous physical gelation upon heating instead of cooling. If the transition in water takes place below the body temperature and the chemicals are biocompatible and biodegradable, such gelling behavior makes the associated physical gels injectable biomaterials with unique applications in drug delivery and tissue engineering etc. Various therapeutic agents or cells can be entrapped in situ and form a depot merely by a syringe injection of their aqueous solutions at target sites with minimal invasiveness and pain. This tutorial review summarizes and comments on this soft matter, especially thermogelling poly(ethylene glycol)-(biodegradable polyester) block copolymers. The main types of injectable hydrogels are also briefly introduced, including both physical gels and chemical gels.