MECHANOBIOLOGICAL GUIDANCE OF BONE DEFECT HEALING ACROSS TEMPORAL AND SPATIAL SCALES

Mechanobiological optimization of fixation devices has made important contributions to the improvement of bone healing strategies over the last decades. However, the rate of non-unions and delayed healing is still at a level that demands innovative approaches, especially in compromised patient situations. Innovative biomaterial approaches that target the early phase of bone healing with soft tissue formation rather than the late phase of mineralized tissue formation addressed so far, open novel avenues for treatment. We and others could show that a timely shift from pro- to anti-inflammation within the first days after trauma is essential for successful healing. However, less is known about the role of early extracellular matrix (ECM) structures that emerge when the initial immune response diminishes. Based on our experience with mechanobiologically optimized titanium mesh scaffolds and resorbable polycaprolactone (PCL) scaffolds, we have evolved towards a mechano-hybrid scaffold concept that provides mechanobiological guidance for both, the early and the later phases of bone defect healing. This is achieved by combining a soft, highly aligned collagen network with a biodegradable 3D printed support structure (PCL). In this concept, the engineered collagen network serves as a guiding structure on the cell level controlling cell invasion and soft tissue (cell/ECM) patterning early in healing. With the degradation of the collagen network after 6–9 weeks, the 3D printed support structure takes over and spatial guidance within the biomaterial transitions from the length scale of cells (10s of μm) to the length scale of tissue (mm to cm). Studies in small and large animals have shown that this concept is successful in preventing the deposition of scar-like collagen fiber patterns but instead induces highly aligned collagen fiber bundles serving as a template for tissue mineralization. Most recently, we have learned how translating such innovative biomaterial concept into clinical usage is challenged by regulatory requirements that are mainly made for conventional material concepts. Our concept is designed to target the treatment of critical sized bone defects but also smaller bone voids, lesions or osteotomies and corrections (e.g. opening wedge HTO), or joint fusions replacing the need for autologous bone grafting. Here, we aim at showcasing the power of next-generation biomaterial solutions based on mechanobiological principles that enable endogenous tissue regeneration and avoid the use of autologous tissue or growth factors that both have side effects for patients.