Abstract

Polymeric scaffolds such as hydrogels can be engineered to restore, maintain, or improve impaired tissues and organs. However, most hydrogels require surgical implantation that can cause several complications such as infection and damage to adjacent tissues. Therefore, developing minimally invasive strategies is of critical importance for these purposes. Herein, we developed several injectable cryogels made out of hyaluronic acid and gelatin for tissue-engineering applications. The physicochemical properties of hyaluronic acid combined with the intrinsic cell-adhesion properties of gelatin can provide suitable physical support for the attachment, survival, and spreading of cells. The physical characteristics of pure gelatin cryogels, such as mechanics and injectability, were enhanced once copolymerized with hyaluronic acid. Reciprocally, the adhesion of 3T3 cells cultured in hyaluronic acid cryogels was enhanced when formulated with gelatin. Furthermore, cryogels had a minimal effect on bone marrow dendritic cell activation, suggesting their cytocompatibility. Finally, in vitro studies revealed that copolymerizing gelatin with hyaluronic acid did not significantly alter their respective intrinsic biological properties. These findings suggest that hyaluronic acid-co-gelatin cryogels combined the favorable inherent properties of each biopolymer, providing a mechanically robust, cell-responsive, macroporous, and injectable platform for tissue-engineering applications.

Highlights

  • The aim of tissue and regenerative engineering is to replace damaged, degenerated, or defective tissues using scaffolds, cells, and signaling molecules [1,2,3,4,5,6]

  • Through a combination of physical and imaging characterizations, cell viability, and biological properties evaluation, we showed that Hyaluronic acid (HA)-co-Gelatin cryogels have significantly improved properties when compared to cryogels made from each polymer individually

  • HAGM, MA-gelatin, and HA-co-Gelatin cryogels were successfully fabricated under different conditions

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Summary

Introduction

The aim of tissue and regenerative engineering is to replace damaged, degenerated, or defective tissues using scaffolds, cells, and signaling molecules [1,2,3,4,5,6]. Polymeric scaffolds can be engineered using hydrogels that are made up of highly hydrophilic and crosslinked three-dimensional (3D). Traditional hydrogels often exhibit a nanoporous network that can limit cell motility, proliferation, and survival, as well as poor mechanical flexibility [10,11,12,13,14,15]. Cryogels, a unique class of hydrogels prepared via cryopolymerization, exhibit large tunable interconnected macropores, high elasticity, and flexibility [15,16,17,18,19]. A variety of extracellular matrix (ECM) components and other biopolymers can be used to generate bioinspired cryogels for tissue engineering applications [17,19,23,24,25]

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