Rapid Bone Regeneration Research Articles

Switch-on mode of bioenergetic channels regulated by curcumin-loaded 3D composite scaffold to steer bone regeneration

Metabolic energy to steer osteoblastic differentiation of bone marrow mesenchymal stem cells (BMSCs) could be a promising therapeutic target for bone tissue engineering (BTE), but prior knowledge of this issue is limited. To address bone defects with BTE, we customized a three-dimensional (3D)-printed composite scaffold (Cur@MS) to allow the controlled release of curcumin, which could facilitate the “switch-on” mode of Glucose transporter 1 (GLUT1) in BMSCs. Consequently, bioenergetic channels, i.e. glucose uptake, were “switched on” to activate GLUT1-RUNX2 crosstalk, which was closely orchestrated with bone regeneration. Furthermore, curcumin-induced cholesterol/lipid raft (Cho/LR) was a “sensor” to trigger the “switch” (GLUT1) by directing its spatial distribution into clusters. In contrast, selective inhibition of Cho/LR and GLUT1 led to a “switch-off” mode and compromised bone regeneration in vivo. Overall, the results suggest Cho/LR is a potential target to steer BMSCs and Cur@MS is an ideal BTE material for stimulating rapid bone regeneration.

Hydroxyapatite-coated gelatin microribbon scaffolds induce rapid endogenous cranial bone regeneration in vivo.

Hydroxyapatite (HA) has a composition similar to mineral bone and has been used for coating macroporous scaffolds to enhance bone formation. However, previous macroporous scaffolds did not support minimally invasive delivery. Our lab has reported on gelatin-based microribbon (μRB) shaped hydrogels, which combine injectability with macroporosity and support cranial bone formation in an immunocompromised mouse model. However, gelatin alone was not sufficient to support cranial bone formation in immunocompetent animals. To overcome this challenge, here we evaluated two methods to incorporate HA into gelatin μRB scaffolds using either modified simulated body fluid (mSBF) or commercially available HA nanoparticles (HAnp). HA incorporation and distribution were characterized using scanning electron microscopy and energy-dispersive X-ray spectroscopy. While both methods enhanced MSC osteogenesis and mineralization, the mSBF method led to undesirable reduction in mechanical properties. HAnp-coated μRB scaffolds were further evaluated in an immunocompetent mouse cranial defect model. Acellular HAnp-coated gelatin μRB scaffolds induced rapid and robust endogenous cranial bone regeneration as shown by MicroCT imaging and histology. Co-delivery with exogenous MSCs led to later bone resorption accompanied by increased osteoclast activity. In summary, our results demonstrate the promise of gelatin μRBs with HAnps as a promising therapy for cranial bone regeneration without the need for exogenous cells or growth factors.

The Osteogenic Role of Barium Titanate/Polylactic Acid Piezoelectric Composite Membranes as Guiding Membranes for Bone Tissue Regeneration.

PurposeBiopiezoelectric materials have good biocompatibility and excellent piezoelectric properties, and they can generate local currents in vivo to restore the physiological electrical microenvironment of the defect and promote bone regeneration. Previous studies of guided bone regeneration membranes have rarely addressed the point of restoring it, so this study prepared a Barium titanate/Polylactic acid (BT/PLA) piezoelectric composite membrane and investigated its bone-formation, with a view to providing an experimental basis for clinical studies of guided bone tissue regeneration membranes.MethodsBT/PLA composite membranes with different BT ratio were prepared by solution casting method, and piezoelectric properties were performed after corona polarization treatment. The optimal BT ratio was selected and then subjected to in vitro cytological experiments and in vivo osteogenic studies in rats. The effects on adhesion, proliferation and osteogenic differentiation of the pre-osteoblastic cell line (MC3T3-E1) were investigated. The effect of composite membranes on bone repair of cranial defects in rats was investigated after 4 and 12 weeks.ResultsThe highest piezoelectric coefficient d33 were obtained when the BT content was 20%, reaching (7.03 ± 0.26) pC/N. The value could still be maintained at (4.47±0.17) pC/N after 12 weeks, meeting the piezoelectric constant range of bone. In vitro, the MC3T3-E1 cells showed better adhesion and proliferative activity in the group of polarized 20%BT. The highest alkaline phosphatase (ALP) content was observed in cells of this group. In vivo, it promoted rapid bone regeneration. At 4 weeks postoperatively, new bone formation was evident at the edges of the defect, with extensive marrow cavity formation; after 12 weeks, the defect was essentially completely closed, with density approximating normal bone tissue and significant mineralization.ConclusionThe BT/PLA piezoelectric composite membrane has good osteogenic properties and provides a new idea for guiding the research of membrane materials for bone tissue regeneration.

High-efficient engineering of osteo-callus organoids for rapid bone regeneration within one month

Large bone defects that cannot form a callus tissue are often faced with long-time recovery. Developmental engineering-based strategies with mesenchymal stem cell (MSC) aggregates have shown enhanced potential for bone regeneration. However, MSC aggregates are different from the physiological callus tissues, which limited the further endogenous osteogenesis. This study aims to achieve engineering of osteo-callus organoids for rapid bone regeneration in cooperation with bone marrow-derived stem cell (BMSC)-loaded hydrogel microspheres (MSs) by digital light-processing (DLP) printing technology and stepwise-induction. The printed MSC-loaded MSs aggregated into osteo-callus organoids after chondrogenic induction and showed much higher chondrogenic efficiency than that of traditional MSC pellets. Moreover, the osteo-callus organoids exhibited stage-specific gene expression pattern that recapitulated endochondral ossification process, as well as a synchronized state of cell proliferation and differentiation, which highly resembled the diverse cell compositions and behaviors of developmentally endochondral ossification. Lastly, the osteo-callus organoids efficiently led to rapid bone regeneration within only 4 weeks in a large bone defect in rabbits which need 2–3 months in previous tissue engineering studies. The findings suggested that in vitro engineering of osteo-callus organoids with developmentally osteogenic properties is a promising strategy for rapid bone defect regeneration and recovery.

Enhanced tissue regeneration through immunomodulation of angiogenesis and osteogenesis with a multifaceted nanohybrid modified bioactive scaffold.

Major traumatic tissue defects are common clinical problems often complicated by infection and local vascular dysfunction, processes which hinder the healing process. Although local application of growth factors or stem cells through various tissue engineering techniques are promising methods for the repair of tissue defects, limitations in their clinical application exist. Herein, we synthesized multifaceted nanohybrids composed of Quaternized chitosan (QCS), Graphene oxide (GO), and Polydopamine (PDA; QCS-GO-PDA). Covalent grafting of QCS and GO at a mass ratio of 5:1 (5QCS-1GO) displayed excellent biocompatibility and enhanced osteogenic ability, while addition of PDA (5QCS-1GO-PDA) reduced the level of reactive oxygen species (ROS). 5QCS-1GO-PDA was able to achieve wound tissue regeneration by reducing the inflammatory response and enhancing angiogenesis. Furthermore, Polylactic acid/hydroxyapatite (PLA/HA) composite scaffolds were printed using Selective Laser Sintering (SLS) and the hybrid nanomaterial (5QCS-1GO-PDA) was used to coat the PLA/HA scaffold (5QCS-1GO-PDA@PLA/HA) to be used for rapid bone regeneration. 5QCS-1GO-PDA not only improved angiogenesis and osteogenic differentiation, but also induced M2-type polarization of macrophages and promoted bone regeneration via the BMP2/BMPRs/Smads/Runx2 signaling pathway. The bidirectional enhanced healing ability of the multifaceted nanohybrids 5QCS-1GO-PDA provides a promising method of effectively treating tissue defects.

Orchestration of energy metabolism and osteogenesis by Mg2+ facilitates low-dose BMP-2-driven regeneration

The clinical application of bone morphogenetic protein-2 (BMP-2) is limited by several factors, including ineffectiveness at low doses and severe adverse effects at high doses. To address these efficacy and safety limitations, we explored whether orchestration of energy metabolism and osteogenesis by magnesium ion (Mg2+) could reduce the dose and thereby improve the safety of BMP-2. Our results demonstrated that rapid metabolic activation triggered by BMP-2 was indispensable for subsequent osteogenesis. Moreover, inadequate metabolic stimulation was shown to be responsible for the ineffectiveness of low-dose BMP-2. Next, we identified that Mg2+, as an ''energy propellant", substantially increased cellular bioenergetic levels to support the osteogenesis via the Akt-glycolysis-Mrs2-mitochondrial axis, and consequently enhanced the osteoinductivity of BMP-2. Based on the mechanistic discovery, microgel composite hydrogels were fabricated as low-dose BMP-2/Mg2+ codelivery system through microfluidic and 3D printing technologies. An in vivo study further confirmed that rapid and robust bone regeneration was induced by the codelivery system. Collectively, these results suggest that this bioenergetic-driven, cost-effective, low-dose BMP-2-based strategy has substantial potential for bone repair.

Effects of pore interconnectivity on bone regeneration in carbonate apatite blocks.

Porous architecture in bone substitutes, notably the interconnectivity of pores, is a critical factor for bone ingrowth. However, controlling the pore interconnectivity while maintaining the microarchitecture has not yet been achieved using conventional methods, such as sintering. Herein, we fabricated a porous block using the crystal growth of calcium sulfate dihydrate, and controlled the pore interconnectivity by limiting the region of crystal growth. The calcium sulfate dihydrate blocks were transformed to bone apatite, carbonate apatite (CO3Ap) through dissolution–precipitation reactions. Thus, CO3Ap blocks with 15% and 30% interconnected pore volumes were obtained while maintaining the microarchitecture: they were designated as CO3Ap-15 and CO3Ap-30, respectively. At 4 weeks after implantation in a rabbit femur defect, new bone formed throughout CO3Ap-30, whereas little bone was formed in the center region of CO3Ap-15. At 12 weeks after implantation, a large portion of CO3Ap-30 was replaced with new bone and the boundary with the host bone became blurred. In contrast, CO3Ap-15 remained in the defect and the boundary with the host bone was still clear. Thus, the interconnected pores promote bone ingrowth, followed by replacement of the material with new bone. These findings provide a useful guide for designing bone substitutes for rapid bone regeneration.

Fabrication and evaluation of a BMP-2/dexamethasone co-loaded gelatin sponge scaffold for rapid bone regeneration.

Improving the osteogenic activity of BMP-2 in vivo has significant clinical application value. In this research, we use a clinical gelatin sponge scaffold loaded with BMP-2 and dexamethasone (Dex) to evaluate the osteogenic activity of dual drugs via ectopic osteogenesis in vivo. We also investigate the mechanism of osteogenesis induced by BMP-2 and Dex with C2C12, a multipotent muscle-derived progenitor cell. The results show that the gelatin scaffold with Dex and BMP-2 can significantly accelerate osteogenesis in vivo. It is indicated that compared with the BMP-2 or Dex alone, 100 nM of Dex can dramatically enhance the BMP-2-induced alkaline phosphatase activity (ALP), ALP mRNA expression and mineralization. Further studies show that 100 nM of Dex can maintain the secondary structure of BMP-2 and facilitate recognition of BMP-2 with its receptors on the surface of C2C12 cells. We also find that in C2C12, Dex has no obvious effect on the BMP-2-induced Smad1/5/8 protein expression and the STAT3-dependent pathway, but Runx2-dependent pathway is involved in the Dex-stimulated osteoblast differentiation of BMP-2 both in vitro and in vivo. Based on these results, a potential mechanism model about the synergistic osteoinductive effect of Dex and BMP-2 in C2C12 cells via Runx2 activation is proposed. This may provide a theoretical basis for the pre-clinical application of Dex and BMP-2 for bone regeneration.

Enhancement of Biofunctionalization by Loading Manuka Oil on TiO2 Nanotubes.

Metallic implants (mesh) for guided bone regeneration can result in foreign body reactions with surrounding tissues, infection, and inflammatory reactions caused by micro-organisms in the oral cavity after implantation. This study aimed to reduce the possibility of surgical failure caused by microbial infection by loading antibacterial manuka oil in a biocompatible nanostructure surface on Ti and to induce stable bone regeneration in the bone defect. The manuka oil from New Zealand consisted of a rich β-triketone chemotype, leptospermone, which showed strong inhibitory effects against several bacteria, even at very low oil concentrations. The TiO2 nanotubular layer formed by anodization effectively enhanced the surface hydrophilicity, bioactivity, and fast initial bone regeneration. A concentration of manuka oil in the range of 0.02% to less than 1% can have a synergistic effect on antibacterial activity and excellent biocompatibility. A manuka oil coating (especially with a concentration of 0.5%) on the TiO2 nanotube layer can be expected not only to prevent stenosis of the connective tissue around the mesh and inflammation by microbial infection but also to be effective in stable and rapid bone regeneration.

Three-dimensional mesenchymal stem cell laden scaffold of icariin sustained-release for bone regeneration.

Icariin (ICA)-loaded zein/PLGA nanofiber membrane combined with MSCs was prepared by coaxial electrospinning and bioelectrospraying. SEM and TEM were used to evaluate the surface morphology and microstructure of the fiber membrane. Ultraviolet spectrophotometry was used to detect drug release. A LIVE/DEAD Viability/Cytotoxicity Kit and fluorescence staining were used to detect cell morphology and activity. Alkaline phosphatase and calcium mineralization deposition were used to evaluate the osteoinductive activity of the scaffold. Dynamic mechanical analysis was used to determine the Young's modulus, maximum load, and maximum elongation of the prepared scaffold. Western blot was used to detect the related protein expression in MSCs induced by drug-loaded scaffolds. Good mechanical properties and stability were observed in the prepared drug-loaded scaffolds. SEM showed that there were a considerable number of MSCs dispersed in the scaffold. MSCs were evenly distributed, could grow evenly between fibers, and were arranged orderly along the fibers. Sustained release of ICA confers cell laden scaffold higher ALP activity and ECM mineral deposition through Runx2, OPN and OCN pathways. Isotropic sustained release of ICA grant cell laden scaffolds rapid bone regeneration compacity which can provide a good osteogenic environment for loaded MSCs.

Injectable platelet-rich fibrin (albumin gel and liquid platelet-rich fibrin)

This article provides review on Injectable Platelet-Rich Fibrin (Albumin Gel and Liquid Platelet-Rich Fibrin). The current findings suggest that AlbPRF has regeneration characteristics that are caused by the slow and steady release of growth factors contained in liquid PRF via albumin gel breakdown. Future research is needed to thoroughly define the degrading features of Alb-PRF in vivo and to investigate potential therapeutic uses in other domains of medicine. Platelet concentrates are easy to apply in clinical practice and offer potential benefits including rapid wound healing and bone regeneration, and can therefore be considered to be new therapeutic adjuvants. In dental implant surgery they are used in bone reconstruction prior or concomitant to implant procedures, and also for dental extraction socket preservation.

Three-dimensional (3D), macroporous, elastic, and biodegradable nanocomposite scaffold for in situ bone regeneration: Toward structural, biophysical, and biochemical cues integration

Although bone tissue with remarkable healing capabilities, the rapid and successful bone regeneration continues to present a challenge because that the influence factors for bone healing are multifaceted, especially for massive bone defects. From a cell/material interactions point of view, integrating multiple cues into one biomaterial is considered as a promising approach in the clinical treatment of bone defects thanks to the provided multiple stimuli. Herein, 3D macroporously elastic biodegradable nanocomposite bone scaffolds (PCSG) were successfully developed based on poly(citrate-siloxane) (PCS) hybrid elastomer and reduced graphene oxide (rGO). The PCSG scaffolds combine with structure (3D, largely open and interconnected pore architecture, high porosity), biophysics (high mechanical properties, roughness surface, piezoelectricity property), and biochemistry cues (silica cross-linked network, Si ions release). Experiments demonstrate that the structurally, biophysically, and biochemically biomimetic properties of PCSG scaffolds are beneficial for triggering cell adhesion, proliferation, matrix mineralization , osteogenic differentiation of osteoblasts (MC3T3-E1) in vitro and significantly promoting in situ bone regeneration in a calvarial bone defect model. The effective and simple strategy of multiple cues integration could pave a universally applicable way in development of bone tissue engineering biomaterials with good osteoinductivity and osteoconductivity for large defects repair, and the reported PCSG scaffolds demonstrate the potential clinic application in fields of bone regeneration and 3D culture of cells. • Integrating structure, biophysics, and biochemistry cues into one bone scaffold for in situ bone regeneration. • The fabrication of 3D bone scaffold with largely open and porosity via the facile sol-gel method. • The proposed bone scaffolds with super Young's modulus not only in dry state but in hydrated condition.

Differences in Fracture Healing Between Female and Male C57BL/6J Mice.

BackgroundMice are increasingly used in fracture healing research because of the opportunity to use transgenic animals. While both, male and female mice are employed, there is no consensus in the literature whether fracture healing differs between both sexes. Therefore, the aim of the present study was to analyze diaphyseal fracture healing in female and male C57BL/6J mice, a commonly used mouse strain in bone research.MethodsFor that purpose, 12-week-old Female (17–20 g) and Male mice (22–26 g) received a standardized femur midshaft osteotomy stabilized by an external fixator. Mice were euthanized 10 and 21 days after fracture and bone healing was analyzed by biomechanical testing, μCT, histology, immunohistochemistry and qPCR.ResultsTen days after fracture, Male mice displayed significantly more cartilage but less fibrous tissue in the fracture callus compared to Female mice, whereas the amount of bone did not differ. At day 21, Male mice showed a significantly larger fracture callus compared to Female mice. The relative amount of bone in the fracture callus did not significantly differ between both sexes, whereas its tissue mineral density was significantly higher in Male mice on day 21, indicating more mature bone and slightly more rapid fracture healing. These results were confirmed by a significantly greater absolute bending stiffness of the fractured femurs of Male mice on day 21. On the molecular level, Male mice displayed increased active β-catenin expression in the fracture callus, whereas estrogen receptor α (ERα) expression was lower.ConclusionThese results suggest that Male mice display more rapid fracture healing with more prominent cartilaginous callus formation. This might be due to the higher weight of Male mice, resulting in increased mechanical loading of the fracture. Furthermore, Male mice displayed significantly greater activation of osteoanabolic Wnt/β-catenin signaling, which might also contribute to more rapid bone regeneration.

An Innovative Bioceramic Bone Graft with Platelet-Rich Plasma for Rapid Bone Healing and Regeneration in a Rabbit Model

This study aimed to investigate the effect of combining an innovative bioceramic α-calcium sulfate hemihydrate (α-CSH, CaSO4⋅0.5H2O) bone graft and platelet-rich plasma (PRP) to accelerate bone healing and regeneration in a rabbit model. The bone graft material was implanted bilaterally on rabbit’s artificially maxillary sinus defects: the right maxillary sinus received α-CSH, while α-CSH combine with PRP (α-CSH/PRP) was grafted in left site. The quantity and quality of bone formation after implantation were analyzed radiographically and histologically at 1, 2, and 3 weeks. The micro-computed tomographic results indicated that the bone density of sinus implanted with α-CSH increased and defect volume decreased most after 2 weeks. In histological analysis, both hematoxylin and eosin and Masson trichrome staining of α-CSH/PRP displays better bone healing and regeneration progress than α-CSH after 2 weeks implantation. Therefore, the innovative α-CSH combined with PRP was revealed to be useful in accelerating bone healing and regeneration for the successful defect treatment.

Advanced Strategies of Biomimetic Tissue-Engineered Grafts for Bone Regeneration.

The failure to repair critical-sized bone defects often leads to incomplete regeneration or fracture non-union. Tissue-engineered grafts have been recognized as an alternative strategy for bone regeneration due to their potential to repair defects. To design a successful tissue-engineered graft requires the understanding of physicochemical optimization to mimic the composition and structure of native bone, as well as the biological strategies of mimicking the key biological elements during bone regeneration process. This review provides an overview of engineered graft-based strategies focusing on physicochemical properties of materials and graft structure optimization from macroscale to nanoscale to further boost bone regeneration, and it summarizes biological strategies which mainly focus on growth factors following bone regeneration pattern and stem cell-based strategies for more efficient repair. Finally, it discusses the current limitations of existing strategies upon bone repair and highlights a promising strategy for rapid bone regeneration.

Does closed treatment of paediatric mandibular condyle fractures result in restitutional remodelling?

The treatment of paediatric mandibular condylar fracture (PMCF) is typically non-operative. The purpose of this study was to determine if non-operative management of PMCF results in a new condylar process of normal morphology to regenerate after closed treatment (restitutional remodelling). The specific aim of the study was to observe restitutional remodelling (RM) in PMCF and review the literature. The investigators designed and implemented a retrospective study on paediatric patients (age<12) with unilateral or bilateral condyle fractures treated with non-operative treatment between January 2005 and July 2015. Patients with complete records and at least 1-year follow-up were included in the study. Primary outcome variable was RM and secondary outcome variables were occlusion, maximal incisal opening (MIO), displacement, infection, facial asymmetry, and signs of temporomandibular joint ankylosis (TMJA). The study evaluated 41 patients {n=57 PMCF, (m:f-35:6)} of unilateral (n=25) and bilateral (n=16) PMCF. Fractured condyles remodelled to normal morphology in all the cases at follow-up. The Wilcoxon test revealed a statistically significant difference in MIO from the preoperative value to postoperative (p=0.001). Occlusion (except 1) was satisfactory in all cases, at follow-up with no gross facial asymmetry. There was no sign of infection at the surgical site (anterior mandible). None of the patients showed signs of TMJA at follow-up. The result of the present study demonstrates that RM of condylar fracture occurs with non-operative management. Non-operative management should be the point of care in PMCF, owing to the rapid RM, bone regeneration, and satisfactory outcome. Review of the literature also supports closed treatment.

A comparative study on silicon nitride, titanium and polyether ether ketone on mouse pre-osteoblast cells.

The current study provides more insights about the surface bioactivity of the silicon nitride (Si3N4) as a potential candidate for bone regeneration in craniofacial and orthopaedic applications compared with conventional implantation materials. Current skeletal reconstructive materials such as titanium and polyether ether ketone (PEEK) are limited by poor long-term stability, biocompatibility and prolonged healing. Si3N4 is an FDA-approved material for an intervertebral spacer in spinal fusion applications. It is biocompatible and has antimicrobial properties. Here, we hypothesize that Si3N4 was found to be an osteoconductive material and conducts the growth, differentiation of MC3T3-E1 cells for extracellular matrix deposition, mineralization and eventual bone regeneration for craniofacial and orthopaedic applications. MC3T3-E1 cells were used to study the osteoblastic differentiation and mineralization on sterile samples of Si3N4, titanium alloy and PEEK. The samples were then analysed for extracellular matrix deposition and mineralization by FTIR, Raman spectroscopy, SEM, EDX, Alizarin Red, qRT-PCR and ELISA. The in vitro study indicates the formation of collagen fibres and mineral deposition on all three sample surfaces. There was more profound and faster ECM deposition and mineralization on Si3N4 surface as compared to titanium and PEEK. The FTIR and Raman spectroscopy show formation of collagen and mineral deposition at 30 days for Si3N4 and titanium and not PEEK. The peaks shown by Raman for Si3N4 resemble closely to natural bone. Results also indicate the upregulation of osteogenic transcription factors such as RUNX2, SP7, collagen type I and osteocalcin. The authors concluded that Si3N4 rapidly conducts mineralized tissue formation via extracellular matrix deposition and biomarker expression in mouse calvarial pre-osteoblast cells. Thus, this study confirms that the bioactive Si3N4 could be a potential material for craniofacial and orthopaedic applications leading to rapid bone regeneration that resemble the natural bone structure.

Bidirectional differentiation of BMSCs induced by a biomimetic procallus based on a gelatin-reduced graphene oxide reinforced hydrogel for rapid bone regeneration

Developmental engineering strategy needs the biomimetic composites that can integrate the progenitor cells, biomaterial matrices and bioactive signals to mimic the natural bone healing process for faster healing and reconstruction of segmental bone defects. We prepared the gelatin-reduced graphene oxide (GOG) and constructed the composites that mimicked the procallus by combining the GOG with the photo-crosslinked gelatin hydrogel. The biological effects of the GOG-reinforced composites could induce the bi-differentiation of bone marrow stromal cells (BMSCs) for rapid bone repair. The proper ratio of GOG in the composites regulated the composites' mechanical properties to a suitable range for the adhesion and proliferation of BMSCs. Besides, the GOG-mediated bidirectional differentiation of BMSCs, including osteogenesis and angiogenesis, could be activated through Erk1/2 and AKT pathway. The methyl vanillate (MV) delivered by GOG also contributed to the bioactive signals of the biomimetic procallus through priming the osteogenesis of BMSCs. During the repair of the calvarial defect in vivo, the initial hypoxic condition due to GOG in the composites gradually transformed into a well-vasculature robust situation with the bi-differentiation of BMSCs, which mimicked the process of bone healing resulting in the rapid bone regeneration. As an inorganic constituent, GOG reinforced the organic photo-crosslinked gelatin hydrogel to form a double-phase biomimetic procallus, which provided the porous extracellular matrix microenvironment and bioactive signals for the bi-directional differentiation of BMSCs. These show a promised application of the bio-reduced graphene oxide in biomedicine with a developmental engineering strategy.

A Comparative Study of Platelet-Rich Fibrin and Platelet-Rich Fibrin with Hydroxyapatite to Promote Healing of Impacted Mandibular Third Molar Socket.

The purpose of this study was to compare the efficacy of platelet-rich fibrin (PRF) and platelet-rich fibrin (PRF) with hydroxyapatite (HA) on postoperative pain, swelling, soft tissue healing and osseous regeneration in mandibular third molar extraction socket in human patient. This prospective study included total 40 patients who reported to the Department of Oral and Maxillofacial Surgery (OMFS), Teerthanker Mahaveer Dental College and Research Centre (TMDC&RC), Moradabad (U.P.). Twenty patients each in both the groups of PRF and PRF with HA were included for the management of impacted mandibular 3rd molar extraction sockets and were evaluated for effectiveness. Evaluation was done on the basis of following parameters pain and swelling at time interval of 1st, 3rd, 7th day, soft tissue healing at time interval of 3rd, 7th, 14th day and osseous regeneration at time intervals of 1st, 3rd, 6th month postoperatively. Pain and swelling were less in the PRF with HA group when compared to PRF group. Soft tissue healing was better in the PRF with HA group compared to the PRF group. The result of the study shows rapid bone regeneration in the extraction socket treated with the PRF with HA group when compared with the PRF group. Also there was less postoperative discomfort in the PRF with HA-treated group. PRF a mitogenic promoter together with a bone graft forms a scaffolding, promotes early healing thus being creating beneficial for the patient and is also economic.

Polyetheretherketone with Citrate Potentiated Influx of Copper Boosts Osteogenesis, Angiogenesis, and Bacteria-Triggered Antibacterial Abilities

Because of the increasing use of biomedical implants, implants associated infections are becoming more prevalent and cause increased morbidity and significant higher healthcare cost. As it is a race for the surface between cells and microbes, achieving a rapid bone regeneration and osseointegration, especially when confronted with implants associated infections, is the primary goal. Herein, we develop a promising solution using porous polyetheretherketone (PEEK) implants incorporated with copper-citrate nanoclusters via bioinspired polydopamine, it can deliver a high dose of bactericides only when and where bacteria appear to eradicate bacteria and release a small amount of copper/citrate under physiological environment to promote osteogenesis and angiogenesis in vitro and in vivo. The synergistic effect between copper and citrate, which is that citrate can facilitate a 2-fold influx of copper into cells, not only heightened the bacteria-killing ability but also encouraged the osteogenesis and angiogenesis performances of implants. This present work provides an effective method to control infections while promoting osseointegration simultaneously, which will show tremendous clinical application and can be a solution to current challenges facing orthopedics.