Injectable Natural Polymer Hydrogels for Treatment of Knee Osteoarthritis

Abstract

Osteoarthritis (OA) is a serious chronic and degenerative disease that increasingly occurs in the aged population. Its current clinical treatments are limited to symptom relief and cannot regenerate cartilage. Although a better understanding of OA pathophysiology has been facilitating the development of novel therapeutic regimen, delivery of therapeutics to target sites with minimal invasiveness, high retention, and minimal side effects remains a challenge. Biocompatible hydrogels have been recognized to be highly promising for controlled delivery and release of therapeutics and biologics for tissue repair. In this review, the current approaches and the challenges in OA treatment, and unique properties of injectable natural polymer hydrogels as delivery system to overcome the challenges are presented. The common methods for fabrication of injectable polysaccharide‐based hydrogels and the effects of their composition and properties on the OA treatment are detailed. The strategies of the use of hydrogels for loading and release cargos are also covered. Finally, recent efforts on the development of injectable polysaccharide‐based hydrogels for OA treatment are highlighted, and their current limitations are discussed.

Recent Developments in Hyaluronic Acid-Based Hydrogels for Cartilage Tissue Engineering Applications

“…Except for the aforementioned properties, it is important to mention that HA can be chemically modified at various sites (e.g., carboxyl, hydroxyl (primary or secondary) or N -acetyl groups) [ 48 ]. More specifically, hydroxyl groups can be modified by esterification and ether/hemiacetal/carbamate formation, whereas carboxyl groups can be modified by amidation, esterification, Ugi condensation and oxidation [ 46 , 49 ]. Finally, the modification reactions of N -acetyl groups involve deacetylation, hemiacetylation, hemiacetal formation and amidation [ 41 ].…”

Microcarriers in application for cartilage tissue engineering: Recent progress and challenges

“…In addition, they can be performed in a minimally invasive fashion at the site of the defect and easily conform to any shapes, especially in joint diseases. This malleability provides a 3D platform for releasing agents, cell proliferation, and increasing lubricity [ 294 ]. In these MCs systems, viscosity decreases when shear strain is increased, allowing the possibility that MCs could flow during the injection [ 295 , 296 ].…”

Polymeric Hydrogels for Controlled Drug Delivery to Treat Arthritis

“…However, hydrogels prepared from natural polymers suffer from poor mechanical strength and accelerated degradation characteristics. Furthermore, it is difficult to manage batch-to-batch variation in order to control the molecular weight range of natural polymers [ 14 ]. Natural polymeric materials can be classified as peptide/protein-based, polysaccharide-based, and protein–polysaccharide-based polymers.…”

“…Divalent cations such as calcium ions (Ca 2+ ) are often used to prepare hydrogels, where replacement of the Na + ions of G-blocks with Ca 2+ ions and the bending of glucuronic groups occur, forming an egg-box structure. However, ionic cross-linked alginate hydrogels exhibit insufficient mechanical strength, slow biodegradation, and poor cell adhesion, limiting their use in clinical applications [ 14 , 43 ].…”