Biomater Sci. 2026 Jul 27. doi: 10.1039/d6bm00766j. Online ahead of print.
ABSTRACT
Orthopedic diseases impose heterogeneous therapeutic demands, ranging from symptomatic control of inflammation and pain to intra-articular drug delivery, cartilage repair, bone regeneration, and prevention of implant-associated infection. Although hydrogels are widely investigated as tunable biomaterials for these applications, their translational potential is often discussed primarily in terms of polymer composition or crosslinking chemistry. This review argues that delivery modality provides a clinically useful framework for evaluating orthopedic hydrogel systems, but translational success depends on the combined influence of material properties, mechanical requirements, degradation behavior, biological integration, manufacturability, and regulatory feasibility. Hydrogel patches, injectable hydrogels, and implantable hydrogels differ in tissue access, mechanical competence, payload capacity, residence time, invasiveness, and regulatory feasibility. Here, we critically compare these three delivery paradigms across major orthopedic indications. Hydrogel patches are best positioned for localized analgesic and anti-inflammatory therapy but remain poorly suited for deep regenerative delivery because of skin-barrier limitations. Injectable hydrogels can offer a strong balance between minimally invasive administration and localized therapeutic control, particularly for intra-articular disease and irregular defects, but require improved retention, mechanical stability, and predictable gelation. Implantable hydrogels can provide architectural and mechanical control for focal bone and osteochondral repair when designed as structural or composite systems, yet their clinical adoption is constrained by surgical burden, manufacturing complexity, and long-term durability requirements. By shifting the discussion from material cataloguing to indication- and delivery-modality-driven design, this review provides a balanced framework for evaluating orthopedic hydrogel technologies and identifies practical translational priorities related to tissue access, mechanical durability, biological response, manufacturing, and clinical feasibility.
PMID:42507101 | DOI:10.1039/d6bm00766j