<p>Biomimetic piezoelectric nanocomposite membranes synergistically enhance osteogenesis of deproteinized bovine bone grafts</p>

Abstract

Purpose: The combination of a bone graft with a barrier membrane is the classic method for guided bone regeneration (GBR) treatment. However, the insufficient osteoinductivity of currently-available barrier membranes and the consequent limited bone regeneration often inhibit the efficacy of bone repair. In this study, we utilized the piezoelectric properties of biomaterials to enhance the osteoinductivity of barrier membranes. Methods: A flexible nanocomposite membrane mimicking the piezoelectric properties of natural bone was utilized as the barrier membrane. Its therapeutic efficacy in repairing critical-sized rabbit mandible defects in combination with xenogenic grafts of deproteinized bovine bone (DBB) was explored. The nanocomposite membranes were fabricated with a homogeneous distribution of piezoelectric BaTiO 3 nanoparticles (BTO NPs) embedded within a poly(vinylidene fluoridetrifluoroethylene) (P(VDF-TrFE)) matrix. Results: The piezoelectric coefficient of the polarized nanocomposite membranes was close to that of human bone. The piezoelectric coefficient of the polarized nanocomposite membranes was highly stable, with more than 90% of the original piezoelectric coefficient (d 33 ) remaining up to 28 days after immersion in culture medium. Compared with commercially-available polytetrafluoroethylene (PTFE) membranes, the polarized BTO/P(VDF-TrFE) nanocomposite membranes exhibited higher osteoinductivity (assessed by immunofluorescence staining for runt-related transcription factor 2 (RUNX-2) expression) and induced significantly earlier neovascularization and complete mature bone-structure formation within the rabbit mandible critical-sized defects after implantation with DBB Bio-Oss® granules. Conclusion: Our findings thus demonstrated that the piezoelectric BTO/P(VDF-TrFE) nanocomposite membranes might be suitable for enhancing the clinical efficacy of GBR.

Role of YAP/TAZ in Cell Lineage Fate Determination and Related Signaling Pathways

“…While some studies indicated that YAP activation enhances osteogenesis, other studies reported contrary results. In two separate studies by our research group, we found that YAP activation in rat bone marrow-derived MSCs is associated with osteogenesis (Bai et al, 2019;Wei et al, 2019). Pan et al (2018) demonstrated that conditional knockout of YAP expression by the osteoblast lineage in mice reduced osteogenic differentiation and cell proliferation, but promoted adipocyte formation, which in turn led to trabecular bone loss.…”

“…Other adult stem cells in which YAP plays an integral role in self-renewal and maintenance of the "stemness" phenotype include neural stem cells (Han et al, 2015;Bao et al, 2017), muscle satellite cells (Judson et al, 2012), and intestinal stem cells (Imajo et al, 2015;Kim H. B. et al, 2017). These will be discussed in greater detail in sections "Role of YAP/TAZ in Neurogenesis and Neuroregeneration, " "Role of YAP/TAZ in Myogenic Differentiation and Skeletal Muscle Regeneration, " and (Hong et al, 2005;Suh et al, 2012Suh et al, , 2014Yang et al, 2013;, the role of YAP in osteogenic differentiation is controversial (Seo et al, 2013;Sen et al, 2015;Pan et al, 2018;Zhu W. Q. et al, 2018;Bai et al, 2019;Lin et al, 2019;Wei et al, 2019). The role of TAZ in the osteogenesis of MSCs was first reported by Hong et al (2005), who found that TAZ co-activates gene transcription by RUNX2, an upstream regulator of osteogenesis, while at the same time repressing gene transcription by PPARγ that directs murine bone marrow MSCs into the adipocyte lineage.…”

“…The stimulatory effect of YAP/TAZ activity on the proliferation of neural stem/progenitor cells may offer a basis for potential therapeutic strategies to promote neuroregeneration. For example, Bai et al (2019) showed that inhibition of LATS1, a core component of the Hippo signaling pathway, increases YAP nuclear translocation, which in turn attenuates neuronal apoptosis and neurological impairment in a rat traumatic brain injury model. Also, Zhang et al (2017) showed that stem cell niche-derived laminin-511 promotes midbrain dopaminergic neuron survival in response to oxidative stress through YAP activation, and that LM511-YAP signaling increases the expression of transcription factors associated with midbrain dopaminergic neuron identity, such as PITX3 and LMX1A.…”

“…There is abundant evidence for key roles of YAP/TAZ in the osteogenic differentiation pathway of primary osteoblasts and various types of adult stem cells, especially bone marrow-derived MSCs. While TAZ activation is consistently associated with osteogenesis ( Hong et al, 2005 ; Suh et al, 2012 , 2014 ; Yang et al, 2013 ; Zhu Y. et al, 2018 ), the role of YAP in osteogenic differentiation is controversial ( Seo et al, 2013 ; Sen et al, 2015 ; Pan et al, 2018 ; Zhu W. Q. et al, 2018 ; Bai et al, 2019 ; Lin et al, 2019 ; Wei et al, 2019 ).…”

A sericin/ graphene oxide composite scaffold as a biomimetic extracellular matrix for structural and functional repair of calvarial bone

“…Bio-Oss®, a deproteinized bovine bone, has been applied in clinical bone transplantation due to its osteoconductive activity. Nevertheless, Bio-Oss® is extracted from cancellous bone, which makes it not optimal for repairing dense bone defects 41. Therefore, development of biocompatible and biodegradable artificial bone substitutes capable of BMSCs recruitment and osteogenic differentiation is highly desired.…”