Smart Polymeric Hydrogels for Cartilage Tissue Engineering: A Review on the Chemistry and Biological Functions

Abstract

Stimuli responsive hydrogels (SRHs) are attractive bioscaffolds for tissue engineering. The structural similarity of SRHs to the extracellular matrix (ECM) of many tissues offers great advantages for a minimally invasive tissue repair. Among various potential applications of SRHs, cartilage regeneration has attracted significant attention. The repair of cartilage damage is challenging in orthopedics owing to its low repair capacity. Recent advances include development of injectable hydrogels to minimize invasive surgery with nanostructured features and rapid stimuli-responsive characteristics. Nanostructured SRHs with more structural similarity to natural ECM up-regulate cell-material interactions for faster tissue repair and more controlled stimuli-response to environmental changes. This review highlights most recent advances in the development of nanostructured or smart hydrogels for cartilage tissue engineering. Different types of stimuli-responsive hydrogels are introduced and their fabrication processes through physicochemical procedures are reported. The applications and characteristics of natural and synthetic polymers used in SRHs are also reviewed with an outline on clinical considerations and challenges.

Injectable hydrogels and nanocomposite hydrogels for cartilage regeneration

“…In the case of physical crosslinking, hydrogels have transient junctions that arise either from polymer chain entanglements or physical interactions such as ionic interactions, hydrogen bonds, hydrophobic interactions, or crystal formation . In chemical crosslinking, the junctions are permanent as a result of various chemical reactions, like radical polymerization, Michael addition, Schiff‐base reaction, photo‐polymerization, enzyme‐catalyzed polymerization, azide‐alkyne cycloaddition reactions . While chemical crosslinking results in higher stability and mechanical strength of hydrogels, there is a need of chemical modification or addition of crosslinking entities in vivo .…”

Rotational barriers of carbamate‐protected amine crosslinkers for hydrogels: A combined experimental and computational study

“…Hydrogels are physically or chemically cross‐linked polymer networks, which contain a large amount of water . The resulting soft elastic materials are suitable for applications in tissue engineering, medical devices, drug delivery, or artificial muscles .…”

“…Hydrogels are physically or chemically cross‐linked polymer networks, which contain a large amount of water . The resulting soft elastic materials are suitable for applications in tissue engineering, medical devices, drug delivery, or artificial muscles . Small molecule crosslinkers are particularly interesting for such hydrogels because their size, rigidity, charge state, and noncovalent interactions can control the elasticity, mechanical strength, and water binding efficiency of the hydrogels.…”

In situ polymerized hyperbranched polymer reinforced poly(acrylic acid) hydrogels

“…The suitability of a hydrogel for a given application depends on the mechanical properties that are affected by the environmental conditions such as temperature, pH level and ionic strength, magnetic and electric fields as well as the monomer type and crosslinking agents. [7][8][9] Among various types of hydrogels, poly acrylate polymers such as poly acrylic acid (PAA), with distinctive absorptivity properties, have the most versatile structure to enhance their practical utility in everyday life applications such as filtration, water remediation, diapers and hygiene products, cosmetics, wound dressings, medical waste solidification and metal ion removal. [10][11][12][13][14] From extensive studies evaluating different properties of PAA hydrogels, such as swelling, 15 adhesion, 16 diffusion, 17 physico-chemical 18 and mechanical 19 properties, it has been revealed that the greatest concern about these types of hydrogels is their poor mechanical properties.…”