Surface Chemistry of Nanoscale Mineralized Collagen Regulates Periodontal Ligament Stem Cell Fate

Abstract

The interplay between stem cells and their extracellular microenvironment is of critical importance to the stem cell-based therapeutics in regenerative medicine. Mineralized collagen is the main component of bone extracellular matrix, but the effect of interfacial properties of mineralized collagen on subsequent cellular behaviors is unclear. This study examined the role of surface chemistry of nanoscale mineralized collagen on human periodontal ligament stem cell (hPDLSC) fate decisions. The intrafibrillarly mineralized collagen (IMC), fabricated by a biomimetic bottom-up approach, showed a bonelike hierarchy with nanohydroxyapatites (HAs) periodically embedded within fibrils. The infrared spectrum of the IMC showed the presence of phosphate, carbonate, amide I and II bands; and infrared mapping displayed uniform and higher spatial distribution of mineralization in the IMC. However, the distribution of the phosphate group differed far from that of the amide I group in the extrafibrillarly mineralized collagen (EMC), in which flowerlike HA clusters randomly depositing around the surface of the fibrils. Moreover, a large quantity of extrafibrillar HAs covered up the C═O stretch and N-H in-plane bend, resulting in substantial reduction of amide I and II bands. Cell experiments demonstrated that the hPDLSCs seeded on the IMC exhibited a highly branched, osteoblast-like polygonal shape with extended pseudopodia and thick stress fiber formation; while cells on the EMC displayed a spindle shape with less branch points and thin actin fibril formation. Furthermore, the biocompatibility of EMC was much lower than that of IMC. Interestingly, even without osteogenic induction, mRNA levels of major osteogenic differentiation genes were highly expressed in the IMC during cultivation time. These data suggest that the IMC with a similar nanotopography and surface chemistry to natural mineralized collagen directs hPDLSCs toward osteoblast differentiation, providing a promising scaffold in bone tissue regeneration.

Osseointegration effect of biomimetic intrafibrillarly mineralized collagen applied simultaneously with titanium implant: A pilot in vivo study

“…We have previously reported on the fabrication of hierarchical, intrafibrillarly mineralized collagen with distinct nanostructures mimicking the natural bone for use in bone tissue engineering according to the principle of a biomimetic strategy (Feng et al, ; Lian et al, ; Liao, Cui, Zhang, & Feng, ; Xu et al, ; Zhang et al, ). IMC materials have shown impressive promoting effects on osteogenic differentiation and bone regeneration both in vitro and in vivo in studies by our group and others (Feng et al, ; Fu et al, ; Lian et al, ; Liu et al, ; Qiu et al, ; Xu et al, ; Zhang et al, ), suggesting that IMC may be an ideal bone scaffold material in bone tissue engineering. Therefore, we propose that the use of IMC with a titanium (Ti) implant placed simultaneously may be a promising strategy for jawbone defect reconstruction that avoids the donor site morbidity associated with the use of autografts and provides immediate improvement in dental function.…”

“…IMC materials have shown impressive promoting effects on osteogenic differentiation and bone regeneration both in vitro and in vivo in studies by our group and others (Feng et al, 2016;Fu et al, 2016;Lian et al, 2013;Liu et al, 2016;Qiu et al, 2015;Xu et al, 2016;Zhang et al, 2018), suggesting that IMC may be an ideal bone scaffold material in bone tissue engineering. Therefore, we propose that the use of IMC with a titanium (Ti) implant placed simultaneously may be a promising strategy for jawbone defect reconstruction that avoids the donor site morbidity associated with the use of autografts and provides immediate improvement in dental function.…”

“…The EMC can only produce similar chemical properties but not the surface chemistry and nanostructure of bone extracellular matrix; therefore, the strength of EMC is insufficient. Intrafibrillar mineralization (IMC) has been shown to be a predominant factor to the biomechanics of natural bone, and thus, synthesis of mineralized collagen with intrafibrillar HA is recognized as a crucial factor for imitating bone extracellular matrix (Feng et al, ; Fu et al, ; Lian et al, ; Liu et al, ; Qiu et al, ; Xu et al, ; Zhang et al, ). We have previously reported on the fabrication of hierarchical, intrafibrillarly mineralized collagen with distinct nanostructures mimicking the natural bone for use in bone tissue engineering according to the principle of a biomimetic strategy (Feng et al, ; Lian et al, ; Liao, Cui, Zhang, & Feng, ; Xu et al, ; Zhang et al, ).…”

“…The EMC can only produce similar chemical properties but not the surface chemistry and nanostructure of bone extracellular matrix; therefore, the strength of EMC is insufficient. Intrafibrillar mineralization (IMC) has been shown to be a predominant factor to the biomechanics of natural bone, and thus, synthesis of mineralized collagen with intrafibrillar HA is recognized as a crucial factor for imitating bone extracellular matrix (Feng et al, 2016;Fu et al, 2016;Lian et al, 2013;Liu et al, 2016;Qiu et al, 2015;Xu et al, 2016;Zhang et al, 2018).…”

Biomineralization‐Inspired Material Design for Bone Regeneration

“…Quantification of osteogenic gene expression showed upregulation of OPN, COL1A1, and BMP2 mRNA on the intrafibrillar mineralized collagen as compared to the controls. Moreover, alizarin red staining showed more pronounced mineralization on the scaffolds with intrafibrillar mineralization …”