Bio-Oss®/Avitene™ composite scaffold promotes maxillofacial bone regeneration via early osteoimmunomodulation of BM-MSCs: an in vitro and clinical study

Inflammation is an important biological process to be considered in designing successful biomaterial-based therapeutics. Indeed, prolonged inflammation can result in delayed wound healing and, in some cases, may cause the rejection of the biomaterial together with additional tissue damage. Mesenchymal stem cells (MSCs) participate in this critical intercellular communication to modulate bone healing. In this study, MSCs were employed as in vitro model in order to evaluate the biological performances, in terms of immune response, of Bio-Oss (R)/Avitene (TM) composite scaffold. Moreover, new bone formation was evaluated in patients undergoing maxillomandibular osteotomy for skeletal malocclusion, facial asymmetry, or aesthetic indications, using a Bio-Oss (R)/Avitene (TM) composite scaffold. The early inflammatory response of human bone marrow derived-mesenchymal stem cells (BM-MSCs) was investigated in vitro analysing the gene expression of IL-6 and IL-8 using Droplet Digital PCR and the release of cytokines, chemokines, and growth factors using Bio-Plex approach. Clinical evaluation was performed using Cone Beam Computed Tomography (CBCT). In vitro, Bio-Oss (R)/Avitene (TM) decreases the IL-6 expression, quantified with Droplet Digital PCR approach. Bio-Plex reveals that the protein levels of MCP-1 and IL-6 were reduced, while IL-4, IL-8 and VEGF were increased by the scaffold in cells up to day 7. CBCT assessment in patients demonstrated stable outcomes, supporting the potential for long-term aesthetic restoration of the zygomatic region. These findings indicate that Bio-Oss (R)/Avitene (TM) possesses immunomodulatory potential and is capable of directing anti-inflammatory, immune-mediated responses associated with bone regrowth for the treatment of dentofacial deformities through orthognathic surgery.