Promotion of osteointegration under diabetic conditions by a silk fibroin coating on 3D-printed porous titanium implants via a ROS-mediated NF-κB pathway.

Clinical evidence indicates the compromised application of titanium implants (TIs) in diabetics, associated with reactive oxygen species (ROS) overproduction at the bone-implant interface. Silk fibroin (SF) has displayed impressive biocompatibility in the application of biomedical material and optimal anti-diabetic effects in oriental medicine. We proposed that SF-coated titanium implants (STIs) could alleviate diabetes-induced compromised osteointegration, which has rarely been reported before.

Ophiopogonin D improves osteointegration of titanium alloy implants under diabetic conditions by inhibition of ROS overproduction via Wnt/β-catenin signaling pathway.

A high failure rate of titanium implants in diabetic patients has been indicated in clinical evidences. Excessive oxidative stress at the bone-implant interface plays an important role in the impaired osteointegration under diabetic conditions. While the underlying mechanisms remain unknown and the targeted treatments are urgently needed.

Lactic acid of PLGA coating promotes angiogenesis on the interface between porous titanium and diabetic bone.

The diabetes-related high failure risk for endosseous implants needs efficacious methods to improve osteointegration on the bone-implant interface (BII). Poly(lactic-co-glycolic) acid (PLGA) is widely used in tissue engineering but its effects on the BII in diabetes remain unclear. To clarify this issue, 3D-printed porous titanium implants (TI) with and without PLGA coating were fixed in the bone defects of sheep in vivo, and vascular endothelial cells (VEC) and osteoblasts were incubated on the implant surface under normal conditions (NC) and diabetic conditions (DC) in vitro.

Angiogenesis impairment by the NADPH oxidase-triggered oxidative stress at the bone-implant interface: Critical mechanisms and therapeutic targets for implant failure under hyperglycemic conditions in diabetes.

Unlabelled: Mechanism underlying the diabetes-induced poor osteointegration of implants remains elusive, making it a challenge to develop corresponding solutions. Here, we studied the role of angiogenesis in the diabetes-induced poor bone repair at the bone-implant interface (BII) and the related mechanisms. In vivo, titanium screws were implanted in the femurs of mice, and, in vitro, vascular endothelial cell (VEC) was cultured on titanium surface.

Involvement of FAK-mediated BMP-2/Smad pathway in mediating osteoblast adhesion and differentiation on nano-HA/chitosan composite coated titanium implant under diabetic conditions.

Chitosan (CS)-based hydroxyapatite (HA) composites have emerged as a novel strategy for promoting bone regeneration. Here nanophase HA/CS composite coated porous titanium implants (nCT) were fabricated and their biological behavior under diabetic conditions was investigated. We proposed that the focal adhesion kinase (FAK)-mediated BMP-2/Smad pathway played a role in mediating the promotive effect of nCTs on osteoblast adhesion and differentiation under diabetes-induced high reactive oxygen species (ROS) condition.

Adiponectin improves the osteointegration of titanium implant under diabetic conditions by reversing mitochondrial dysfunction via the AMPK pathway in vivo and in vitro.

Unlabelled: Diabetes-induced reactive oxygen species (ROS) overproduction would result in compromised osteointegration of titanium implant (TI) and high rate of implant failure, yet the underlying mechanisms remain elusive. Adiponectin (APN) is a fat-derived adipocytokine with strong antioxidant, mitochondrial-protective and anti-diabetic efficacies. We hypothesized that mitochondrial dysfunction under diabetes may account for the oxidative stress in osteoblasts and titanium-bone interface (TBI) instability, which could be ameliorated by APN.

Magnesium Ions Promote the Biological Behaviour of Rat Calvarial Osteoblasts by Activating the PI3K/Akt Signalling Pathway.

Magnesium has been investigated as a biodegradable metallic material. Increased concentrations of Mg around magnesium implants due to biodegradation contribute to its satisfactory osteogenic capacity. However, the mechanisms underlying this process remain elusive.

Relationship between sample volumes and modulus of human vertebral trabecular bone in micro-finite element analysis.

Micro-finite element (μFE) models have been widely used to assess the biomechanical properties of trabecular bone. How to choose a proper sample volume of trabecular bone, which could predict the real bone biomechanical properties and reduce the calculation time, was an interesting problem. Therefore, the purpose of this study was to investigate the relationship between different sample volumes and apparent elastic modulus (E) calculated from μFE model.

Optimal sample volumes of human trabecular bone in μCT analysis within vertebral body and femoral head.

Trabecular bones of different skeletal sites have different bone morphologies. How to select an appropriate volume of region of interest (ROI) to reflect the microarchitecture of trabecular bone in different skeletal sites was an interesting problem. Therefore, in this study, the optimal volumes of ROI within vertebral body and femoral head, and if the relationships between volumes of ROI and microarchitectural parameters were affected by trabecular bone morphology were studied.

Temporal changes of microarchitectural and mechanical parameters of cancellous bone in the osteoporotic rabbit.

This study was aimed at elucidating the temporal changes of microarchitectural and mechanical parameters of cancellous bone in the osteoporotic rabbit model induced by ovariectomy (OVX) combined with glucocorticoid (GC) administration. Osteoporotic (OP) group received bilateral OVX combined with injections of GC, while sham group only received sham operation. Cancellous bone quality in vertebrae and femoral condyles in each group was assessed by DXA, μCT, nanoindentation, and biomechanical tests at pre-OVX and 4, 6, and 8 weeks after injection.

Insulin improves osteogenesis of titanium implants under diabetic conditions by inhibiting reactive oxygen species overproduction via the PI3K-Akt pathway.

Clinical evidence indicates that insulin therapy improves implant survival rates in diabetic patients; however, the mechanisms responsible for this effect are unknown. Here, we test if insulin exerts anti-oxidative effects, thereby improving diabetes-associated impaired osteoblast behavior on titanium implants. To test this hypothesis, we cultured primary rabbit osteoblasts in the presence of titanium implants and studied the impact of treatment with normal serum (NS), diabetic serum (DS), DS + insulin, DS + tempol (a superoxide dismutase mimetic), DS + insulin + tempol, and DS + insulin + wortmannin.

Osseointegration of chitosan coated porous titanium alloy implant by reactive oxygen species-mediated activation of the PI3K/AKT pathway under diabetic conditions.

Chitosan coated porous titanium alloy implant (CTI) is demonstrated a promising approach to improve osseointegration capacity of pure porous titanium alloy implant (TI). Since chitosan has been demonstrated to exhibit antioxidant activity, we propose CTI may ameliorate the ROS overproduction, thus reverse the poor osseointegration under diabetic conditions, and investigate the underlying mechanisms. Primary rat osteoblasts incubated on the TI and the CTI were subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and DS + LY294002 (a PI3K/AKT-specific inhibitor).

Preventive effect of crocin on osteoporosis in an ovariectomized rat model.

The purpose of this study was to investigate the therapeutic effects of crocin on ovariectomy-induced osteoporosis in rats. Female Sprague-Dawley rats were randomly assigned to a sham-operated group (sham) and five ovariectomy (OVX) subgroups, that is, OVX with vehicle (OVX), OVX with 17β-estradiol (E 2, 25 μg/kg/day), and OVX with graded crocin doses (5, 10, or 20 mg/kg/day). Daily oral administration of E 2 or crocin started 4 weeks after OVX and lasted for 16 weeks.

The promotion of osteointegration under diabetic conditions using chitosan/hydroxyapatite composite coating on porous titanium surfaces.

Composited Chitosan/Hydroxyapatite (CS/HA) material coated on titanium surface (cTi) is a promising approach to produce biomaterials with better osseointegration capacity, but its bio-performance under diabetic conditions and the mechanisms involved remain elusive. We propose that the alterations in the Wnt/β-catenin pathway may play a role in mediating the improvement effect of cTi on diabetes-induced impaired implant osteointegration. To confirm the hypothesis, primary rat osteoblasts incubated on Ti and cTi were subjected to normal serum (NS), diabetic serum (DS), DS + Wnt3a (a specific Wnt agonist) and DS + Dkk1 (a specific Wnt antagonist) treatment.

Repair of segmental bone defect using Totally Vitalized tissue engineered bone graft by a combined perfusion seeding and culture system.

Background: The basic strategy to construct tissue engineered bone graft (TEBG) is to combine osteoblastic cells with three dimensional (3D) scaffold. Based on this strategy, we proposed the "Totally Vitalized TEBG" (TV-TEBG) which was characterized by abundant and homogenously distributed cells with enhanced cell proliferation and differentiation and further investigated its biological performance in repairing segmental bone defect.

Methods: In this study, we constructed the TV-TEBG with the combination of customized flow perfusion seeding/culture system and β-tricalcium phosphate (β-TCP) scaffold fabricated by Rapid Prototyping (RP) technique.

Effect of reactive oxygen species overproduction on osteogenesis of porous titanium implant in the present of diabetes mellitus.

Clinical evidence indicates diabetes as a majorrisk factor for titaniumimplant treatment with high failure rates and poor osteointegration, but the underlying mechanism involved remains elusive.We hypothesize that reactive oxygen species (ROS) overproduction may contribute to the impaired osteogenesis of porous titanium implants (pTi) under diabetic conditions. To test this hypothesis, we culturedprimary rabbit osteoblasts onto pTi and studied the cellular performance when subjected to normal serum (NS), diabetic serum (DS), DS + NAC (a potent ROS inhibitor) and NS + H(2)O(2)(an oxidant).

Evaluation of biological properties of electron beam melted Ti6Al4V implant with biomimetic coating in vitro and in vivo.

Background: High strength porous titanium implants are widely used for the reconstruction of craniofacial defects because of their similar mechanical properties to those of bone. The recent introduction of electron beam melting (EBM) technique allows a direct digitally enabled fabrication of patient specific porous titanium implants, whereas both their in vitro and in vivo biological performance need further investigation.

Methods: In the present study, we fabricated porous Ti6Al4V implants with controlled porous structure by EBM process, analyzed their mechanical properties, and conducted the surface modification with biomimetic approach.

Influence of architecture of β-tricalcium phosphate scaffolds on biological performance in repairing segmental bone defects.

Background: Although three-dimensional (3D) β-tricalcium phosphate (β-TCP) scaffolds serve as promising bone graft substitutes for the segmental bone defect treatment, no consensus has been achieved regarding their optimal 3D architecture.

Methods: In this study, we has systematically compared four types of β-TCP bone graft substitutes with different 3D architectures, including two types of porous scaffolds, one type of tubular scaffolds and one type of solid scaffolds, for their efficacy in treating segmental bone defect in a rabbit model.

Results: Our study has demonstrated that when compared to the traditional porous and solid scaffolds, tubular scaffolds promoted significantly higher amount of new bone formation in the defect regions as shown by X-ray, micro CT examinations and histological analysis, restored much greater mechanical properties of the damaged bone evidenced by the biomechanical testing, and eventually achieved the complete union of segmental defect.