No abstract

Soft gingiva is often compromised in gingival health; however, the underlying biological mechanisms remain unknown. Extracellular matrix (ECM) stiffness is involved in the progression of various fibroblast-related inflammatory disorders via cellular mechanotransduction. Gingival stiffness might regulate cellular mechanotransduction-mediated proinflammatory responses in gingival fibroblasts. This in vitro study aims to investigate the effects of substrate stiffness on proinflammatory responses in human gingival fibroblasts (hGFs). The hGFs isolated from two healthy donors cultured on type I collagen-coated polydimethylsiloxane substrates with different stiffnesses, representing soft (5 kPa) or hard (25 kPa) gingiva. Expression levels of proinflammatory mediators, prostaglandin E2 or interleukin-1β, in hGFs were significantly higher with the soft substrate than with the hard substrate, even without and with lipopolysaccharide (LPS) to induce inflammation. Expression levels of gingival ECM and collagen cross-linking agents in hGFs were downregulated more with the soft substrate than with the hard substrate through 14 days of culture. The soft substrate suppressed the expression of mechanotransduction-related transcriptional factors and activated the expression of inflammation-related factors, whereas the hard substrate demonstrated the opposite effects. Soft substrate induced proinflammatory responses and inhibition of ECM synthesis in hGFs by inactivating cellular mechanotransduction. This supports the importance of ECM stiffness in gingival health.

No abstract

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.