Lacunar Bone-Inspired Biodegradable Constructs: Towards Mini-Invasive Bone Repair

Advancements in the field of medicine have resulted in increased life expectancy but have also led to a rise in age-related illnesses, with osteoporosis being one of the most prevalent and widespread diseases. Each year, approximately 9 million fragility fractures occur globally, imposing a significant economic and psychosocial burden for disease management. While accidents and bone tumors directly cause pain and deformity, bone fragility often remains undetected, gradually deteriorating quality of life and creating a pressing need for effective regenerative strategies.<br/>Despite notable progress in microsurgical techniques in recent decades, achieving satisfactory functional and structural repair of damaged bone tissue remains challenging. Although bone tissue possesses intrinsic regrowth and self-restoration capabilities to some extent, the injured bones frequently fail to regain their load-bearing function, resulting in fracture nonunion. Current approaches for treating large bone injuries involve the use of autografts, allografts, and scaffolds, but none of these methods are entirely satisfactory due to specific limitations. These limitations include reduced bioactivity, potential spread of pathogens, inflammation, the need for additional surgery, limited availability, inappropriate shape and size, and a lack of monitoring for newly formed bone. In particular, difficulties in detecting bone-scaffold interactions and understanding the complex relationships between bone formation and local scaffold geometry are currently impeding the clinical applicability of minimally invasive constructs for bone healing.<br/>To overcome these challenges, we propose the design of a novel construct for bone healing that has the potential for scalability, while addressing the current geometric, biological, and monitoring issues. The geometry of the construct is inspired by the natural lacunar micro-porosity and interconnectivity found in human bones, facilitating an improved cell seeding process. The constructs are fabricated using silk fibroin and seeded with mesenchymal stem cells. Two different culture media are considered: the state-of-the-art fetal bovine serum (FBS) and the human platelet lysate (hPL). To assess the mechanical response of cellularized constructs, we employ image-guided failure assessment within a synchrotron using a newly developed X-ray and human eye testing equipment, performing micro-compression tests on the seeded constructs. Scans are acquired at various time frames, corresponding to increasing levels of applied displacement to the construct.<br/>To evaluate the interplay between bone regeneration and the architecture of the silk fibroin scaffold, we utilize neural networks (NN). With a NN accuracy of 0.92, our findings demonstrate the following: i) there is a statistically significant correlation (p&lt;0.05) between pore density and bone formation; ii) constructs seeded with hPL exhibit enhanced bone regeneration (+26%) compared to those seeded with FBS; iii) pore shape may play a crucial role in modulating bone remodeling.<br/>The unprecedented resolution of synchrotron imaging, coupled with the ability to gain novel insights into the mechanical response of constructs for bone healing, enables us to elucidate the intricate connections between scaffold geometry, woven bone formation, and the restoration of mechanical function. Future endeavors will focus on the utilization of shape-responsive materials in construct design, allowing the shape of the construct to be adapted according to specific requirements and needs.