Bone‐like tissue formation on a biomimetic titanium surface in an explant model of osteoconduction

Abstract

The clinical use of titanium in dental and orthopedic applications is limited. Over recent years, implant surfaces have undergone numerous modifications to enhance bone integration. In this study, we experimented a bioactive titanium using a simple chemical and moderate heat treatment that led to the formation of a bone-like apatite layer on its surface in simulated body fluids. We used a bone explant model to demonstrate that cells can migrate from the explants and subsequently differentiate to form a mineralized nodular structure. Furthermore, these cells expressed alkaline phosphatase, bone sialoprotein, osteocalcin and the transcription factor, Runx2. Using this model of osteoconduction, we showed that bioactive titanium bonds directly to bone, while pure titanium cannot. These findings show the importance of implant surface composition in promoting osteogenic cell differentiation and subsequent apposition of the bone matrix, allowing strong bonds to form. This model could be particularly beneficial to closely mimic bone formation adjacent to endosseous implants.

A preliminary study of the dental implant therapy—initial osteogenesis of Human Mesenchymal Stem (HMS0014) cells on titanium discs with different surface modifications—

“…Many studies on the endosseous dental implantation have demonstrated that pure Ti and Ti-alloy IP surface modified with bioactive substrates acquired an immediately mechanical stability to enhance cell attachment, improve the host-to-IP response and thereby optimize osseointegration 2,5,13,[26][27][28][29][30] . Additionally, many histological studies indicated that osseointegration begins with recruitment and migration of osteogenic lineage cells, which adhered and spread, proliferated, and subsequently differentiated into osteoblast (Ob)-like cells which initiated osteogenesis by cell and tissue ingrowth onto the IP surface; the mature Ob-like cells changed in shape concomitant with differentiation and expressed osteocalcin gene in the mineralizing phase [1][2][3][30][31][32][33] .…”

“…Additionally, many histological studies indicated that osseointegration begins with recruitment and migration of osteogenic lineage cells, which adhered and spread, proliferated, and subsequently differentiated into osteoblast (Ob)-like cells which initiated osteogenesis by cell and tissue ingrowth onto the IP surface; the mature Ob-like cells changed in shape concomitant with differentiation and expressed osteocalcin gene in the mineralizing phase [1][2][3][30][31][32][33] . Meanwhile, interfacing specific receptor proteins (e.g., integrins) and cytoskeleton proteins (e.g., actin filaments) have been elucidated to be proteins closely related with the development of focal contacts, which play important roles in signal transduction and thereby induce adhesion, spreading, cell migration and consequently regulate cell growth and differentiation of the Ob-like cells attached on the IP substratum [32][33][34] .…”

“…On the other hand, the present fluorescent immunohistology of the expression of α v integrin and F-actin indicated that we engineered actinrich HMS0014 cells on the Ti/Ti-alloy discs with different modifications (i.e., Disc-AO, Disc-HA and Disc-SPI). The proliferating cells actively migrated and dispersed along the bioactive interface with participation to bind, initiate and establish focal adhesions with the modified substratum within 180 minutes of culture 30,33,[35][36][37] . Furthermore, we confirmed that the ECM of the osteogenic linage HMS0014 cells in experimental (under inducing condition) monolayer cultures showed an increase of osteocalcin activity through the experimental term, and the cells were actively proliferated differentiating into Obs with an abrupt and significant increase of ALP activity and Ca volume in particular at 14 days experiment.…”

Bioengineered titanium surfaces affect the gene-expression and phenotypic response of osteoprogenitor cells derived from mouse calvarial bones

“…We previously proposed and characterised an in vitro model using foetal calvaria bone explants that mimic in vivo bone formation on endosseous dental implants (Isaac et al, 2009). Using this model of osteoconduction, we showed that alkali-and heat-treated titanium soaked in SBF creates a favourable template for osteoblast migration, differentiation and bone nodule formation.…”

A fine structure study on osteogenesis of mesenchymal stem cells cultured with a 3D collagen scaffold

“…Furthermore, there have many studies revealed that seeding osteogenic MSCs on 3D scaffold or IPs coated with collagen could enhance cell-biomaterial interactions to promote the growth, differentiation and osteoconduction on Ti dental IPs [1,5,7,[12][13][14][15]. We preliminary estimated that Cellmatrix Type I-A fibrillar component formed an interwoven scaffold network for hard tissue formation by MSCs to surround Ti-IP test samples [11].…”