Scaffold-Based Drug Delivery Systems for Diseased Tissue Treatment and Regeneration

Abstract

This review provides an overview of scaffold-based drug delivery systems (DDSs) designed to simultaneously achieve treatment and regeneration of diseased tissues. Conventional scaffolds for bone tissue engineering have primarily been developed as structural supports for space maintenance and tissue regeneration. While these materials are effective for relatively simple defects, their therapeutic capacity remains limited in complex pathological conditions accompanied by infection, inflammation, impaired blood supply, and abnormal bone metabolism. In contrast, scaffold-based DDSs represent a next-generation therapeutic platform in which the scaffold functions not only as a structural support but also as a localized delivery system for therapeutic agents. By incorporating and sustainably releasing antibodies, proteins, small-molecule drugs, and functional inorganic ions, these systems actively modulate the local pathological microenvironment and promote simultaneous tissue treatment and regeneration. This localized strategy enables high therapeutic concentrations at the target site while minimizing systemic exposure and adverse effects. A critical design concept of scaffold-based DDSs is multiscale structural control ranging from macro- to nano-scale architectures. Macroscale structures, such as interconnected pores and aligned channels, regulate cell infiltration, vascular invasion, and spatial guidance of newly formed tissues. Meanwhile, micro- and nanoscale surface structures strongly influence specific surface area, interfacial reactivity, adsorption capacity, and sustained release behavior of therapeutic agents. These hierarchical structural features also affect cell adhesion, differentiation, osteoclast activity, and tissue maturation, thereby integrating therapeutic and regenerative functions within a single biomaterial platform. Particular emphasis is placed on carbonate apatite-based honeycomb scaffolds developed by the authors as representative examples of scaffold-based DDSs. These include localized antibody DDSs using anti-sclerostin antibodies for osteoporotic bone defects, silver ion-based DDSs for antibacterial therapy, and copper ion-based DDSs for angiogenesis enhancement and the treatment of medication-related osteonecrosis of the jaw. These systems demonstrate the potential of scaffold-based DDSs as advanced therapeutic platforms capable of addressing complex pathological tissue defects in both dental and orthopedic fields. Finally, future perspectives are discussed regarding the design principles, clinical translation, and broader applications of scaffold-based DDSs for pathological tissue regeneration.