Laminin 332-functionalized coating to regulate the behavior of keratinocytes and gingival mesenchymal stem cells to enhance implant soft tissue sealing

Abstract

Peri-implant epithelial sealing is the first line of defense against external pathogens or stimuli; hence, an essential process to prevent peri-implantitis. Laminin 332 (LN332) is the main component of the internal basal lamina and participates in peri-implant epithelial sealing by forming hemidesmosomes with integrin α6β4. In this work, poly (D, L-lactide) (PDLLA)-LN332 composite coating was successfully constructed by a method similar to layer-by-layer assembly, displaying staged LN332 release for as long as 28 days. The PDLLA-LN332 composite coating can activate the intracellular PI3K-Akt pathway via binding to cellular integrin α6β4, which can promote adhesion, migration, and proliferation of HaCaT cells and further enhance the expression of keratinocyte hemidesmosome-related molecules, including integrin α6β4, LN332, and plectin. Furthermore, the PDLLA-LN332 composite coating can promote the adhesion, spreading, and proliferation of gingival mesenchymal stem cells（GMSCs） and accelerate their epithelial differentiation. Therefore, the PDLLA-LN332 composite coating can enhance implant soft tissue sealing, warranting further in vivo study.

CREB3L2 Regulates Hemidesmosome Formation during Epithelial Sealing

“…3E-H). The PI3K/AKT signaling pathway regulates cell adhesion and HD-related molecule expression (Liu et al 2019(Liu et al , 2022. Therefore, Western blot analysis was conducted to further verify the expression of AKT signaling pathway-related proteins (Fig.…”

“…Although osseointegration of the implants with the bone has achieved great success in clinical practice, soft tissue diseases around implants, such as peri-implantitis, can affect the soft and hard tissues around implants, leading to implant failure eventually (Salvi et al 2017;Schwarz et al 2018). It is currently common practice to modify the surface of implants with peptides derived from LM332 (El-Ghannam et al 1998;Abdallah et al 2017;Liu et al 2019Liu et al , 2022. While this attempt appears to be effective in vitro, it may encounter problems such as coating instability, rapid degradation, and immunological concerns in vivo.…”

“…HDs consist mainly of ITGA6B4, plectin, and type XVII collagen (COL17A1/BP180) and are highly specialized epithelial attachment structures mediated by integrins, which enables cells to adhere firmly to the ECM (Walko et al 2015). When ITGA6B4 binds to ligand LM332, it can activate the intracellular phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB; also known as AKT) signaling pathway, which plays a key role in regulating cell growth, viability, adhesion, proliferation, and survival in cells (Yang et al 2019;Liu et al 2022). Studies have shown that the activation of the PI3K/AKT signaling pathway through implant surface modification can promote HD formation and improve soft tissue integration around implants (Liu et al 2019(Liu et al , 2020(Liu et al , 2022.…”

“…When ITGA6B4 binds to ligand LM332, it can activate the intracellular phosphatidylinositol 3-kinase (PI3K)/protein kinase B (PKB; also known as AKT) signaling pathway, which plays a key role in regulating cell growth, viability, adhesion, proliferation, and survival in cells (Yang et al 2019;Liu et al 2022). Studies have shown that the activation of the PI3K/AKT signaling pathway through implant surface modification can promote HD formation and improve soft tissue integration around implants (Liu et al 2019(Liu et al , 2020(Liu et al , 2022. However, little is currently known about which signaling pathway plays a role in MSCs regulating PIE sealing.…”

Biomimetic Strategy to Enhance Epithelial Cell Viability and Spreading on PEEK Implants

“…A few studies explored the idea of improving soft tissue integration of titanium with proteins such as collagen I, laminins, − fibronectin, BM peptides, and laminin- and ameloblastin-derived peptides . Although all these works showed improved biological integration, they did not investigate if the coatings influenced protein adsorption, which is an essential step in determining how tissues respond to implant surface chemistry.…”