Work

Sclerostin Antibody-Loaded Dense Collagen Hydrogels Promote Critical-Size Bone Defect Repair

Year: 2024

Type: article

Abstract: The management of extensive bone loss remains a clinical challenge. Numerous studies are underway to develop a combination of biomaterials, biomolecules and stem cells to address this challenge. In particular, the systemic administration of antibodies against sclerostin, a regulator of bone formation, was recently shown to enhance the bone repair efficiency of dense collagen hydrogels hosting murine dental pulp stem cells (mDPSCs). The aim of the present study was to assess whether these antibodies, encapsulated and released from collagen hydrogels, could promote craniofacial bone repair by local inhibition of sclerostin. In vitro studies showed that antibody loading did not modify neither the hydrogel structure nor the viability of seeded mDPSCs. When implanted in a critical mouse calvarial bone defect, antibody-loaded DCHs showed repair capabilities similar to acellular unloaded DCHs combined with antibody injections. Importantly, the addition of mDPSCs provided no further benefit. Altogether the local delivery of anti-sclerostin antibodies from acellular dense collagen scaffolds is highly effective for bone repair. The drastic reduction in the required amount of antibody compared to systemic injection should reduce the cost of the procedure, making the here-proposed strategy a promising therapeutic approach for large bone defects repair.Statement of significanceDelivering a monoclonal antibody as close as possible to its target increases its efficacy while reducing the dose required. For this purpose, biomaterials allowing the local delivery of full antibodies have been described but never in the context of bone repair. Here, we demonstrate that dense collagen hydrogels loaded with anti-sclerostin antibodies can play the role of a delivery system while also serving as a scaffold to temporarily fill the bone defect and guide the bone repair process. This study paves the way for the design of improved biomaterials that combine intrinsic bone repair capability with the ability to locally deliver monoclonal antibodies for the treatment of localized bone defects.

Source: ACS Biomaterials Science & Engineering

DOI: 10.1021/acsbiomaterials.4c00883