Injectable in situ forming biodegradable chitosan–hyaluronic acid based hydrogels for cartilage tissue engineering

Abstract

Injectable, biodegradable scaffolds are important biomaterials for tissue engineering and drug delivery. Hydrogels derived from natural polysaccharides are ideal scaffolds as they resemble the extracellular matrices of tissues comprised of various glycosaminoglycans (GAG). Here, we report a new class of biocompatible and biodegradable composite hydrogels derived from water-soluble chitosan and oxidized hyaluronic acid upon mixing, without the addition of a chemical crosslinking agent. The gelation is attributed to the Schiff-base reaction between amino and aldehyde groups of polysaccharide derivatives. In the current work, N-succinyl-chitosan (S-CS) and aldehyde hyaluronic acid (A-HA) were synthesized for preparation of the composite hydrogels. The polysaccharide derivatives and composite hydrogels were characterized by FTIR spectroscopy. The effect of the ratio of S-CS and A-HA on the gelation time, microstructure, surface morphology, equilibrium swelling, compressive modulus, and in vitro degradation of composite hydrogels was examined. The potential of the composite hydrogel as an injectable scaffold was demonstrated by encapsulation of bovine articular chondrocytes within the composite hydrogel matrix in vitro. The results demonstrated that the composite hydrogel supported cell survival and the cells retained chondrocytic morphology. These characteristics provide a potential opportunity to use the injectable, composite hydrogels in tissue engineering applications.

Cell-Derived Polymer/Extracellular Matrix Composite Scaffolds for Cartilage Regeneration, Part 1: Investigation of Cocultures and Seeding Densities for Improved Extracellular Matrix Deposition

“…Motivated by this native structure, a variety of cartilage tissue engineering strategies to date have incorporated ECM, including sponges, coated scaffolds, and hydrogels of glycosaminoglycans (GAGs) or collagen, as well as decellularized tissues. [1][2][3][4][5][6][7][8][9][10][11][12][13] Whereas it is possible to generate ECM-derived scaffolds from components extracted directly from tissues, utilizing cell cultures to generate ECM/polymer composite scaffolds may be a more promising approach. This method has the added benefit of producing constructs with not only structural components, namely the polymeric scaffold and ECM components, but also the inclusion of growth factors and regulatory proteins beneficial for directing tissue regeneration.…”

Hybrid extracellular matrix design for cartilage‐mediated bone regeneration

“…Weight loss study was performed in triplicates (n 5 3) and the percentage of weight loss was calculated as reported in the literature. 43 …”

Bioactive Scaffolds for the Controlled Formation of Complex Skeletal Tissues

“…Cartilage and osteochondral structures have been the main focus of attention for GAGbased scaffolds, as GAGs are particularly important components of cartilage ECM. Tan et al showed the potential of new oxidized hyaluronan/N-succinyl chitosan systems that are able to gel in situ for the delivery of chondrocytes (Tan et al, 2009). Eggelet et al tested a cell-free polyester/hyaluronan scaffold to cover microfractured full-thickness articular cartilage defects in sheep, and achieved significant improvements in histological structure, and in collagen type-II content as detected by immunohistochemistry (Erggelet et al, 2009).…”