Engineering a 3D neuro-into-bone bioprinted model for the study of human skeletal pain mechanisms

Bone pain is a significant clinical challenge that arises from conditions such as fractures, cancer metastases, and osteoporosis. The underlying mechanisms remain poorly understood due to the limitations of current 2D in vitro models and animal studies. This work presents a novel 3D bioprinted model designed to simulate interactions between skeletal tissue and the peripheral nervous system. Human bone marrow stromal cells (HBMSCs) were encapsulated in a Laponite®-based bioink (LAMC) to form the bone construct, while nociceptors derived from induced pluripotent stem cells (iPSCs) were embedded in a neural bioink composed of methacrylate hyaluronic acid (HA-MA) and gelatine methacrylate (GelMA). Crosslinking strategies were optimized to achieve structural stability while maintaining cell viability. The integration of these components demonstrated promising results in recapitulating the complex nociceptive signalling pathways. This model offers a scalable and reproducible platform for studying bone pain mechanisms and testing patient-specific therapies, aiming to bridge the gap between preclinical research and clinical applications.