Mangiferin Induces Post-Implant Osteointegration in Male Diabetic Rats.

Background and Objectives: Hyperglycemia is known to undermine the osteointegration process of implants. In this study, the effects of mangiferin (MF) on the post-implant osteointegration process in a type-II diabetes model were investigated molecularly and morphologically. Materials and Methods: Sprague Dawley male rats were divided into three groups: control, diabetes, and diabetes + MF. All animals were implanted in their tibia bones on day 0. At the end of the 3-month experimental period, the animals' blood and the implant area were isolated. Biochemical measurements were performed on blood samples and micro-CT, qRT-PCR, histological, and immunohistochemical measurements were performed on tibia samples. Results: MF significantly improved the increased glucose, triglyceride-VLDL levels, and liver enzymes due to diabetes. By administering MF to diabetic rats, the osteointegration percentage and bone volume increased while porosity decreased. DKK1 and BMP-2 mRNA expressions and OPN, OCN, and OSN mRNA-protein expressions increased by MF administration in diabetic rats. Additionally, while osteoblast and osteoid surface areas increased with MF, osteoclast and eroded surface areas decreased. Conclusions: The findings of our study indicate that MF will be beneficial to the bone-repairing process and osteointegration, which are impaired by type-II diabetes.

A self-assembled bilayer polypeptide-engineered hydrogel for spatiotemporal modulation of bactericidal and anti-inflammation process in osteomyelitis treatment.

BACKGROUND: Drug resistance of pathogens and immunosuppression are the main causes of clinical stagnation of osteomyelitis. The ideal treatment strategy for osteomyelitis is to achieve both efficient antibacterial and bone healing through spatiotemporal modulation of immune microenvironment. METHODS: In this study, a bilayer hydrogel based on genetically engineered polypeptide AC10A and AC10ARGD was prepared by self-assembly. Ag2S QDs@DSPE-mPEG2000-Ce6/Aptamer (AD-Ce6/Apt) was loaded in the top layer AC10A hydrogel (AA) for antibacterial, and bone marrow-derived mesenchymal stem cells (BMSCs) were loaded in the lower layer AC10ARGD hydrogel (MAR) for bone healing. The AD-Ce6/Apt can be released from the AA hydrogel to target S. aureus before bacterial biofilm formation and achieved significant bactericidal effect under irradiation with a 660 nm laser. Moreover, AD-Ce6/Apt can induce M1 type polarization of macrophages to activate the immune system and eliminate residual bacteria. Subsequently, BMSCs released from the MAR hydrogel can differentiate into osteoblasts and promote the formation of an anti-inflammatory microenvironment by regulating the M2 type polarization of macrophages. The bilayer AA-MAR hydrogel possessed good biocompatibility. RESULTS: The in vitro and in vivo results showed that the AA-MAR hydrogel not only realized efficient photodynamic therapy of S. aureus infection, but also promoted the transformation of immune microenvironment to fulfill the different needs of each stage, which ultimately improved bone regeneration and mechanical properties post-surgery. CONCLUSION: This work presents an approach for spatiotemporal modulation of immune microenvironment in the treatment of osteomyelitis.

Nanocomposite scaffold seeded with mesenchymal stem cells for bone repair.

The mechanical property of bone tissue scaffolds is one of the most important aspects in bone tissue engineering that has remained problematic. In our previous study, we fabricated a three-dimensional scaffold from nano-hydroxyapatite/gelatin (nHA/Gel) and investigated its efficiency in promoting bone regeneration both in vitro and in vivo. In the present study, the effect of adding silicon carbide (SiC) on the mechanical and biological behaviors of the nHA/Gel/SiC and bone regeneration in vivo were determined. nHA and SiC were synthesized and characterized by the X-ray diffraction pattern and transmission electron microscope image. Layer solvent casting, freeze drying, and lamination techniques were applied to prepare these scaffolds. Then, the biocompatibility and cell adhesion behavior of the synthesized nHA/Gel/SiC scaffolds were investigated. For in vivo studies, rats were categorized into three groups: blank defect, blank scaffold, and rat bone marrow mesenchymal stem cells (rBM-MSCs)/scaffold. After 1, 4, and 12 weeks post-injury, the rats were sacrificed and the calvaria were harvested. Sections with a thickness of 5 µm thickness were prepared and stained with hematoxylin-eosin and Masson's Trichrome, and immunohistochemistry was performed. Our results showed that SiC effectively increased the mechanical properties of the nHA/Gel/SiC scaffold. No significant differences were observed in biocompatibility, cell adhesion, and cytotoxicity of the nHA/Gel/SiC in comparison with the nHA/Gel nanocomposite. Based on histological and immunohistochemical studies, both osteogenesis and collagenization were significantly higher in the rBM-MSCs/scaffold group, quantitatively and qualitatively. The present study strongly suggests the potential of SiC as an alternative strategy to improve the mechanical and biological properties of bone tissue engineering scaffolds, and shows that the pre-seeded nHA/Gel/SiC scaffold with rBM-MSCs improves osteogenesis in the engineered bone implant.

Bond Strength and Adhesion Mechanisms of Novel Bone Adhesives.

Bone adhesives offer distinct advantages over the use of screws to attached internal fixation plates (IFPs). As the chemical composition of bone is similar to dentine, it is possible that the types of monomers used to make dentine adhesives could be utilised to affix IFPs to bone. The ability to attach a bio-resorbable IFP to porcine bone was assessed for the monomer 10-methacryloyloxydecyl dihydrogen phosphate (MDP), used either as a homopolymer or a copolymer with urethane dimethacrylate (MDP + U). Additionally, the addition of a priming step (MDP + U + P) was evaluated. The chemical interactions of the monomers with bone were assessed using XRD and imaged using TEM, revealing the formation of nano-layered structures with the MDP primer, something we believe has not been reported on bone. In a 6-week artificial aging study both MDP + U and MDP + U + P demonstrated adequate shear bond strength to affix bio-resorbable IFPs. The cytotoxicity profiles of the adhesive formulations were determined using indirect and direct contact with MC3T3 cells, with indirect conditions suggesting the MDP + U + P is as cytocompatible as the resorbable IFP. The findings of this study suggest our newly developed adhesive has the potential to be used as a bone adhesive to affix bioresorbable IFPs.

Biodegradable and Biocompatible Adhesives for the Effective Stabilisation, Repair and Regeneration of Bone.

Bone defects and complex fractures present significant challenges for orthopaedic surgeons. Current surgical procedures involve the reconstruction and mechanical stabilisation of complex fractures using metal hardware (i.e., wires, plates and screws). However, these procedures often result in poor healing. An injectable, biocompatible, biodegradable bone adhesive that could glue bone fragments back together would present a highly attractive solution. A bone adhesive that meets the many clinical requirements for such an application has yet to be developed. While synthetic and biological polymer-based adhesives (e.g., cyanoacrylates, PMMA, fibrin, etc.) have been used effectively as bone void fillers, these materials lack biomechanical integrity and demonstrate poor injectability, which limits the clinical effectiveness and potential for minimally invasive delivery. This systematic review summarises conventional approaches and recent developments in the area of bone adhesives for orthopaedic applications. The required properties for successful bone repair adhesives, which include suitable injectability, setting characteristics, mechanical properties, biocompatibility and an ability to promote new bone formation, are highlighted. Finally, the potential to achieve repair of challenging bone voids and fractures as well as the potential of new bioinspired adhesives and the future directions relating to their clinical development are discussed.

Pearl Powder-An Emerging Material for Biomedical Applications: A Review.

Pearl powder is a well-known traditional Chinese medicine for a variety of indications from beauty care to healthcare. While used for over a thousand years, there has yet to be an in-depth understanding and review in this area. The use of pearl powder is particularly growing in the biomedical area with various benefits reported due to the active ingredients within the pearl matrix itself. In this review, we focus on the emerging biomedical applications of pearl powder, touching on applications of pearl powder in wound healing, bone repairing, treatment of skin conditions, and other health indications.

Effect of hyaluronic acid on the osseointegration of dental implants.

The mechanism of osseointegration is related to many factors, including the quality of the bone, the biocompatibility and surface characteristics of the implant material, the surgical technique, and functional loading. The purpose of this study was to investigate the effects of hyaluronic acid gel on the osseointegration of implants placed in defined areas of the mandible in rabbits. Hyaluronic acid is known to have an osteoinductive effect during regeneration of bony defects, and we thought that it might also have a favourable effect on osseointegration, a specialised mechanism to heal bone. Ten New Zealand rabbits aged 10 weeks and weighing 2.5-3.0kg were used, and sites for implants that were far enough from the apices of the teeth in the mandibular molar area were chosen. Two cavities were prepared in each rabbit, one (anterior) for the control implant, and one (posterior) for the implant with hyaluronic acid gel (Medical Instinct GmbH, Bovenden). New bone and the osteoid matrix content around the dental implants were evaluated histologically and histomorphometrically two months after the operation, and no significant difference was found between the two groups.

Fabrication of dopamine modified polylactide-poly(ethylene glycol) scaffolds with adjustable properties.

Bio-based polymers have been widely used to be as scaffolds for repairing the bone defects. However, the polymer scaffolds are generally lack of bioactivity and cell recognition site. Seeking effective ways to improve the bioactivity and interaction between materials and tissue or cells is clinically important for long-term performance of bone repair materials. In this work, polylactide-b-poly(ethylene glycol)-b-polylactide (PLA-PEG-PLA, PLEL) tri-block copolymers were firstly synthesized by ring-opening polymerization of lactide using PEG with various molecular weights. Inspired by excellent adhesion of dopamine (DA), a facile and effective method was developed to fabricate polydopamine (PDA) and polydopamine/nano-hydroxyapatite (PDA/n-HA) modified PLEL scaffolds by deposition of PDA and PDA/n-HA coating. The surface structure, degradation rates and mineralization of the modified PLEL scaffolds were investigated, and obviously improved after immobilization of PDA and PDA/n-HA coatings. Moreover, the biocompatible results showed a significant increase in cells viability and adhesion. Therefore, the surface modification with PDA and PDA/n-HA could not only adjust the properties of scaffolds, but also reinforce the interfacial adhesion between the PLEL and cells.

[Repair of segmental bone defects in rabbits' radius with domestic porous tantalum encapsulated with pedicled fascial flap].

Objective: To investigate the effect of domestic porous tantalum encapsulated with pedicled fascial flap on repairing of segmental bone defect in rabbits' radius. Methods: A total of 60 New Zealand white rabbits (aged 6- 8 months and weighing 2.5-3.0 kg) were randomly divided into the experimental group and control group (30 rabbits each group). A 1.5 cm segmental bone defect in right radius was established as the animal model. The porous tantalums encapsulated with pedicled fascial flaps (30 mm×20 mm) were implanted in the created bone defect in the experimental group, and the porous tantalums were only implanted in the control group. X-ray films were observed at the day after operation and at 4, 8, and 16 weeks after operation. Specimens were taken out at 4, 8, and 16 weeks after operation for HE staining and toluidine blue staining observation. The maximum load force and bending strength were detected by three point bending biomechanical test, and the Micro-CT analysis and quantitative analysis of the new bone volume fraction (BV/TV) were performed at 16 weeks after operation to compare the bone defect repair ability in vivo in 2 groups. Results: All incisions healed by first intention without wound infection. At 4, 8, and 16 weeks after operation, the X-ray films showed that the implants were well maintained without apparent displacement. As followed with time, the combination between the implants and host bone became more and more closely, and the fracture line gradually disappeared. HE staining and toluidine blue staining showed that new bone mass and maturity gradually increased at the interface and inside materials in 2 groups, and the new bone gradually growed from the interface to internal pore. At 16 weeks after operation, the three point bending biomechanical test showed that the maximum load force and bending strength in the experimental were (96.54±7.21) N and (91.26±1.76) MPa respectively, showing significant differences when compared with the control group [(82.65±5.65) N and (78.53±1.16) MPa respectively] ( t=3.715, P=0.004; t=14.801, P=0.000). And Micro-CT analysis exhibited that there were a large amount of new bone at the interface and the surface of implant materials and inside the materials. The new bone BV/TV in the experimental group (32.63%±3.56%) was significantly higher than that in control group (25.07%±4.34%) ( t=3.299, P=0.008). Conclusion: Domestic porous tantalum encapsulated with pedicled fascial flap can increase local blood supply, strengthen material bone conduction ability, and promote the segmental bone defect repair.

Improving interfacial adhesion with epoxy matrix using hybridized carbon nanofibers containing calcium phosphate nanoparticles for bone repairing.

Hybridized carbon nanofibers containing calcium phosphate nanoparticles (CNF/CaP) were investigated as osteocompatible nanofillers for epoxy resin. The CNF/CaP was produced by electrospinning mixture solution of polyacrylonitrile and CaP precursor sol-gel, followed by preoxidation and carbonization. The continuous and long CNF/CaP was ultrasonically chopped, mixed into epoxy resin and thermo-cured. Compared to pure CNFs with similar ultrasonication treatment, the shortened CNF/CaP reinforced composites demonstrated significant enhancement in flexural properties of epoxy composites, benefiting from the improved interfacial adhesion between CNF/CaP and resin matrix. The resulting composites also displayed good biocompatibility and sustained calcium ion release, which categorized them as promising materials for bone repairing.

Preparation and characterization of collagen-hydroxyapatite/pectin composite.

Pectin, a kind of plant polysaccharide, was introduced into collagen-hydroxyapatite composite system, and prepared collagen-hydroxyapatite/pectin (Col-HA/pectin) composite in situ. The structure of the composite was investigated by XRD, SEM, and FT-IR. The mechanical properties, water absorption, enzyme degradation, and cytotoxicity of the composite were investigated as well. The results show that the inorganic substance in the composite materials is hydroxyapatite in relatively low crystallinity. A new interface appeared by the interaction among hydroxyapatite and collagen-pectin, and formed smooth fine particles. The mechanical properties, water absorption, enzyme degradation, and cytotoxicity indicate a potential use in bone replacement for the new composite.

Using mesenchymal stem cells as a therapy for bone regeneration and repairing

Bone is a unique tissue which could regenerate completely after injury rather than heal itself with a scar. Compared with other tissues the difference is that, during bone repairing and regeneration, after the inflammatory phase the mesenchymal stem cells (MSCs) are recruited to the injury site and differentiate into either chondroblasts or osteoblasts precursors, leading to bone repairing and regeneration. Besides these two precursors, the MSCs can also differentiate into adipocyte precursors, skeletal muscle precursors and some other mesodermal cells. With this multiline-age potentiality, the MSCs are probably used to cure bone injury and other woundings in the near future. Here we will introduce the recent developments in understanding the mechanism of MSCs action in bone regeneration and repairing.