Applications of Hydrogels in Osteoarthritis Treatment

Abstract

This review critically evaluates advancements in multifunctional hydrogels, particularly focusing on their applications in osteoarthritis (OA) therapy. As research evolves from traditional natural materials, there is a significant shift towards synthetic and composite hydrogels, known for their superior mechanical properties and enhanced biodegradability. This review spotlights novel applications such as injectable hydrogels, microneedle technology, and responsive hydrogels, which have revolutionized OA treatment through targeted and efficient therapeutic delivery. Moreover, it discusses innovative hydrogel materials, including protein-based and superlubricating hydrogels, for their potential to reduce joint friction and inflammation. The integration of bioactive compounds within hydrogels to augment therapeutic efficacy is also examined. Furthermore, the review anticipates continued technological advancements and a deeper understanding of hydrogel-based OA therapies. It emphasizes the potential of hydrogels to provide tailored, minimally invasive treatments, thus highlighting their critical role in advancing the dynamic field of biomaterial science for OA management.

Keywords: Biomaterials; Drug delivery; Hydrogel; Interdisciplinary therapy; Osteoarthritis.

Figure 1

(A) Schematic Diagram of the Pathogenesis of OA and (B) Various Hydrogel Treatments for OA.

Figure 2

(A) Number of SCI indexed publications on various types of source-based hydrogels used in OA treatment. (B) Number of SCI indexed publications comparing injectable hydrogels to other hydrogel-based treatment methods.

Figure 3

Classification and Structural Diagram of Hydrogel Raw Material Sources. Natural hydrogels include hyaluronic acid, alginate, chitosan, and gelatin. Synthetic hydrogels encompass poly(N-isopropylacrylamide), polyvinyl alcohol, polyethylene glycol, and polyacrylic acid hydrogels.

Figure 4

Schematic Diagram of Hydrogel Cross-Linking Methods. (A) Classification and principles of chemical cross-linking in hydrogels. (B) Classification and principles of physical cross-linking in hydrogels. The small balls represent different atoms or ions involved in cross-linking. The gray arrows represent crosslinking reactions. Red and green arrows represent electrostatic forces.

Figure 5

(A) Drugs and bioactive substances in hydrogel delivery systems used for treating OA. (B) Principles and mechanisms of hydrogel treatment for OA.

Figure 6

A possible and feasible method of creation and therapeutic process of hydrogel microneedles for treating OA can be described as follows: After successful loading of drugs or bioactive substances and subsequent crosslinking, hydrogel is formed into a microneedle array using 3D printing technology. These microneedles, exceedingly small in size, are designed to penetrate the stratum corneum, the outermost layer of the skin, without affecting underlying nerves. Specifically engineered for targeted joint areas, these hydrogel microneedles, upon penetrating the skin, facilitate the release of the encapsulated medication into the body, thereby providing more precise and localized treatment for OA [126].

Figure 7

Illustration of the Principles of Microfluidic Technology and Photocuring Molding Technique Using GelMA Hydrogel Microspheres as an Example. GelMA, combined with the desired drugs or bioactive substances, passes through the micro-orifices in the microfluidic device to form uniformly textured microspheres loaded with the drug. These are then solidified and molded under ultraviolet light radiation.

Figure 8

Multiple Responsive Hydrogels for Treating OA. (A) Diagrammatic representation of OA. (B–G) Illustrations depicting the principles of temperature-responsive, mechanical-responsive, pH-responsive, enzyme-responsive, magnetic-responsive, and ROS-responsive hydrogels, respectively. Black arrows represent responsive reactions.

Figure 9

Preparation of Decellularized Matrix Hydrogel Derived from Rat Chondrocytes and Its Application in OA Treatment. Rat cartilage undergoes decellularization to form a sol containing the extracellular matrix of chondrocytes. This is then cross-linked with PEGDA to form an injectable, photosensitive decellularized matrix hydrogel drug delivery system, which gels inside the body under blue light radiation.

Figure 10

Schematic Diagram of Entangled Cross-Linked Protein Hydrogels. The gelation process of entangled protein hydrogels includes four stages: concentration of solution, chemical denaturation, denaturation cross-linking, and renaturation folding.

Figure 11

Schematic Diagram of Superlubricating Hydrogels. The diagram illustrates the design of ball bearing-inspired superlubricated microsphere, which synergistically treats OA in rats. The advent of this hydrogel marks a significant milestone in the treatment of OA, through enhanced hydration lubrication and sustained drug release [144].