The periodontium supports the teeth by dentoalveolar fibrous joints that serve unique oral functions. Endogenous regeneration of the periodontium around
artificial teeth (
dental implants) provides a cost-effective
solution for the extension of healthy life expectancy but remains a challenge in regenerative medicine. Biomimetics can create smart
biomaterials that tune endogenous cells at a tissue-material interface. Here, we created a smart
titanium nanosurface mimicking the surface nanotopography and micromechanical properties of the tooth root cementum (TRC), which is essential for the induction of dentoalveolar fibrous joints to regenerate the periodontium. After
transplantation into the rat renal
capsule, only the
titanium artificial tooth with the TRC-mimetic nanosurface formed a complex dentoalveolar fibrous joint structure, with bone tissue, periodontal ligament (PDL), and TRC, in the decellularized jawbone matrix. TRC-mimetic
titanium implants induce the formation of functional periodontium, even in a jawbone implantation model, which generally causes osseointegration (
ankyloses). In human PDL cells, TRC analogousness in the surface mechanical microenvironment regulates matrix mineralization through
bone sialoprotein expression and
phosphorus metabolism, which are critical for cementogenesis. Therefore, the
titanium nanosurfaces with nanotopographical and mechanical microenvironments mimicking the TRC surface induce dentoalveolar fibrous joints for periodontal regeneration by interfacial tuning of endogenous cells.