A novel bioengineering approach to restoring permanent periodontal inflammatory bone loss

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About 80% of Americans experience periodontitis in their lifetime. Alveolar bone loss leads to loosening or loss of teeth or dental implants that disrupts the most basic daily functions, such as eating and speaking. Various bone grafts are being used to restore alveolar bone loss, but poor prognosis remains a long-standing problem. Autografts are considered the gold standard, but these grafts exhibit significant volume loss in inflammatory conditions. The available amount of material for autografts is limited, and surgical harvesting procedures are often complex and associated with morbidity, pain, and infection at the donor site. Allografts and xenografts have less bone formation capacity than autografts, while they are also associated with risks of infection, disease transmission, and immunological rejection by the host. Synthetic bone grafts such as hydroxyapatite (HAP) and beta-tricalcium phosphate (β-TCP) have also been widely used, mostly in granule or block form. However, none of the existing synthetic bone graft materials exhibit sufficient bone formation capacity to restore inflammatory alveolar bone loss to pre-disease levels. There is a significant unmet medical need for the development of a next-generation bone implant that can effectively regenerate alveolar bone in chronic inflammatory conditions. Alveolar bone almost never spontaneously regenerates in the presence of chronic inflammation. Excess inflammation destroys tissues and supports the growth of pathogens leading to the realization that effective control of microbiome dysbiosis in periodontitis cannot be achieved without effective control of inflammation. Inflammation can be resolved by specialized pro-resolving lipid mediators (SPMs) that can rapidly restore tissue homeostasis to stop the negative feedback loop of infection-inflammation and boost bone regeneration. SPMs effectively regulate inflammation in utero through early childhood, but their production and effectiveness diminish with age. In many instances, chronic inflammatory diseases such as periodontitis are associated with a failure of natural resolution pathways. Here, we aim to develop an innovative 3D printed customized biomimetic and immunomodulatory alveolar bone implant that can provide targeted key biological factors for inflammation modulation and bone regeneration. We will use whitlockite (WH) nanoparticles, the second most abundant bone mineral in humans with excellent bone formation capacity, to develop SPM-delivering bone-mimetic ink material for 3D printing a customized, personalized bone implant that can stably fit into alveolar bone defects to effectively resolve inflammation and boost bone regeneration. During this research project, we will establish a novel bioengineering process for preparing this innovative alveolar bone implant that can later be used by clinicians. The therapeutic effectiveness of the SPM-delivering bone-mimetic implant will be evaluated in a periodontitis model with alveolar bone loss. We envisage that the proposed biomimetic immunomodulatory 3D printed bone implant will significantly improve alveolar bone regeneration in severe inflammatory periodontitis or peri- implantitis and lead to a breakthrough in the treatment of non-healing inflammatory skeletal defects.