Innovations in foot and ankle arthrodesis: Biological and biomaterial approaches to reducing non-union and the challenge of preclinical models

Foot and ankle arthrodesis remains a critical surgical approach for managing end-stage joint disease, yet its success is frequently hindered by the challenge of non-union. Despite advances in surgical techniques, complex cases - such as tibiotalocalcaneal fusion - still face non-union rates as high as 27 %, largely due to the region's unique biomechanical demands and compounded by patient comorbidities and surgical variability. In recent years, orthobiologics and advanced biomaterials have demonstrated significant promise in enhancing fusion outcomes, particularly in high-risk patients with bone defects, metabolic disorders, or a history of infection. However, much of the existing clinical evidence stems from other orthopaedic contexts, with limited high-quality data specific to foot and ankle applications. To bridge this gap and support translational innovation, the development of preclinical models that accurately replicate the physiological and pathological characteristics of the human foot and ankle is essential. This review provides a comprehensive overview of the latest advancements in biologics and biomaterials for foot and ankle arthrodesis, with particular emphasis on hydrogels as next-generation platforms for bone regeneration and targeted drug delivery. Additionally, we critically examine the limitations of current preclinical models in terms of biomechanical compatibility and pathological relevance, highlighting opportunities for future refinement. STATEMENT OF SIGNIFICANCE: Foot and ankle arthrodesis often fails due to non-union in complex, poorly vascularized regions. Emerging biomaterials, such as B2A-coated ceramics and peptide-enhanced grafts, show promise in enhancing fusion outcomes. However, a critical barrier to translation is the lack of preclinical models that reflect the foot and ankle's pathological and mechanical complexity. This review not only surveys advanced orthobiologics but also proposes strategies for developing "negative models" and integrating high-risk conditions to better evaluate fusion efficacy. By bridging biomaterial innovation with model development, it offers a structured path for future research and clinical translation in foot and ankle fusion.