Colloidal Gels with Extracellular Matrix Particles and Growth Factors for Bone Regeneration in Critical Size Rat Calvarial Defects

Abstract

Colloidal gels encapsulating natural materials and exhibiting paste-like properties for placement are promising for filling complex geometries in craniofacial bone regeneration applications. Colloidal materials have demonstrated modest clinical outcomes as bone substitutes in orthopedic applications, but limited success in craniofacial applications. As such, development of a novel colloidal gel will fill a void in commercially available products for use in craniofacial reconstruction. One likely application for this technology is cranial reconstruction. Currently, traumatic brain injury (TBI) is often treated with a hemi-craniectomy, a procedure in which half the cranium is removed to allow the injured brain to swell and herniate beyond the enclosed cranial vault. The use of colloidal gels would allow for the design of a pliable material capable of expansion during brain swelling and facilitate cranial bone regeneration alleviating the need for a second surgery to replace the previously removed hemi-cranium. In the current study, colloidal nanoparticles of hydroxyapatite (HAp), demineralized bone matrix (DBM), and decellularized cartilage (DCC) were combined with hyaluronic acid (HA) to form colloidal gels with desirable rheological properties (τy ≥ 100 Pa). BMP-2 and VEGF growth factors were included to assess extracellular matrix (ECM) contribution of DBM and DCC. The HA-HAp (BMP-2) and HA-HAp-DCC group had 89 and 82% higher bone regeneration compared to the sham group, respectively (p < 0.01). Material retention issues observed may be alleviated by implementing chemical crosslinking. Overall, DCC may be a promising material for bone regeneration in general, and colloidal gels may hold significant potential in craniofacial applications.