Superior Osseointegration Research Articles

Enhancing Bone-Titanium integration through hydrogel coating mediated sequential M1/M2 polarization of interfacial macrophages

Regulating phenotypes of in situ macrophages (Mφ) is a cutting-edge strategy for promoting bone-Titanium (Ti) integration, but what is the most rational modulation manner has long been controversial. Short-term inducing in situ M1 Mφ polarization or inducing in situ M2 Mφ polarization have proven to be capable of promoting osseointegration. However, an increasing number of researches have claimed that sequentially inducing in situ M1/M2 Mφ polarization, compared to the above-mentioned two strategies, could further enhance osseointegration. In this work, we compared the capability of the three different modulation manners to promote osseointegration. Briefly, we anchored a homogeneous Poly(HEMA-co-3APBA)/LUT/SOP hydrogel coating, which could sequentially release pro-inflammatory sophoridine (SOP) molecules and anti-inflammatory luteolin (LUT) molecules through pH mediated conformational transition of phenylboronic acid ester bonds, on the surface of Ti implants. Ti implants coated with the Poly(HEMA-co-3APBA)/SOP hydrogel or the Poly(HEMA-co-3APBA)/LUT hydrogel, which merely released SOP molecules and LUT molecules respectively, were utilized as controls. In vitro Mφ co-culture assays proved the immunoregulation functions of different hydrogel coatings in inducing Mφ polarization, and the rationale behind which was identified to be related to the PI3K-AKT signaling pathways. In addition, the immunoregulation mediated osteogenic differentiation behaviors of bone marrow mesenchymal stem cells (BMSCs) were also investigated. Implantation of as-prepared Ti nails to a rat femur defect model followed by evaluations of H&E staining, Masson staining, immunohistochemical staining, etc. proved the stronger capability to enhance osseointegration of inducing sequential M1/M2 Mφ polarization than short-term inducing in situ M1 Mφ polarization or inducing in situ M2 Mφ polarization. This work not only reported a novel Ti implant with superior osseointegration capability but also will inspire corresponding researches in the future.

The Biocompatibility and the Effect of Titanium and PEKK on the Osseointegration of Customized Facial Implants.

The purpose of this study was to investigate the optimization of computer-aided design/computer-aided manufacturing (CAD/CAM) patient-specific implants for mandibular facial bone defects and compare the biocompatibility and osseointegration of machined titanium (Ma), Sandblasted/Large-grit/Acid-etched (SLA) titanium, and polyetherketoneketone (PEKK) facial implants. We hypothesized that the facial implants made of SLA titanium had superior osseointegration when applied to the gonial angle defect and prevented the senile atrophy of the bone. Histologic findings of the soft-tissue reaction, hard-tissue reaction, and bone-implant contact (BIC (%) of 24 Ma, SLA, and PEKK facial implants at 8 and 12 weeks were investigated. There was no statistical difference in the soft tissue reaction. Bone was formed below the periosteum in all facial implants at 12 weeks and the BIC values were significantly different at both 8 and 12 weeks (p < 0.05). Ma, SLA, and PEKK facial implants are biocompatible with osseointegration properties. SLA can enhance osseointegration and provoke minimal soft tissue reactions, making them the most suitable choice. They provide an excellent environment for bone regeneration and, over the long term, may prevent atrophy caused by an aging mandible. The bone formation between the lateral surface of the facial implant and periosteum may assist in osseointegration and stabilization.

Comprehensive review of PEO coatings on titanium alloys for biomedical implants

Titanium and its alloys are commonly utilized in the biomedical field for fabricating orthopedic and dental implants due to their favorable mechanical, chemical, and biological properties. However, titanium alloys exhibit limited or no bioactivity, necessitating the application of surface functionalization techniques to enhance their functional characteristics suitable for biomedical applications. Plasma Electrolytic Oxidation (PEO) treatment is a simple and versatile surface modification process for valve metals that can add superior osseointegration and bioactive properties to titanium and its alloys. Therefore, this review aims to summarize the mechanisms involved in obtaining porous coatings on the surface of titanium alloys using the PEO method, as well as to outline some of the physicochemical and biological properties of the resulting surfaces. The article discusses the mechanisms of action of bactericidal agents such as copper, silver, and zinc, commonly incorporated into PEO coatings. Finally, the study concludes by discussing remaining challenges and future perspectives that need to be addressed.

Improved Biocompatibility and Osseointegration of Nanostructured Calcium-Incorporated Titanium Implant Surface Treatment (XPEED®).

Surface treatment of implants facilitates osseointegration, with nanostructured surfaces exhibiting accelerated peri-implant bone regeneration. This study compared bone-to-implant contact (BIC) in implants with hydroxyapatite (HA), sand-blasted and acid-etched (SLA), and SLA with calcium (Ca)-coated (XPEED®) surfaces. Seventy-five disk-shaped grade 4 Ti specimens divided into three groups were prepared, with 16 implants per group tested in New Zealand white rabbits. Surface characterization was performed using X-ray diffraction (XRD), field emission scanning electron microscopy (FE-SEM), digital microscopy, and a contact angle analyzer. Cell viability, proliferation, and adhesion were assessed using MC3T3-E1 cells. Apatite formation was evaluated using modified simulated body fluid (m-SBF) incubation. After 4 weeks of healing, the outcomes reviewed were BIC, bone area (BA), removal torque tests, and histomorphometric evaluation. A microstructure analysis revealed irregular pores across all groups, with the XPEED group exhibiting a nanostructured Ca-coated surface. Surface characterization showed a crystalline CaTiO3 layer on XPEED surfaces, with evenly distributed Ca penetrating the implants. All surfaces provided excellent environments for cell growth. The XPEED and SLA groups showed significantly higher cell density and viability with superior osseointegration than HA (p < 0.05); XPEED exhibited the highest absorbance values. Thus, XPEED surface treatment improved implant performance, biocompatibility, stability, and osseointegration.

Histological evaluation of osseointegration between conventional and novel bone-level tapered implants in healed bone-A preclinical study.

To histologically compare osseointegration and crestal bone healing between newly introduced tapered, self-cutting bone-level test implants and tapered bone-level control implants in sites with fully healed sites. Sixty-six implants (33 test, 33 control) were placed 1 mm subcrestally in a minipig model and underwent qualitative histologic and quantitative histometric analyses after 3, 6 and 12 weeks of submerged healing. The primary and secondary outcomes were the bone-to-implant contact (BIC) and first bone-to-implant contact (fBIC). Outcomes between the test and control implants were statistically compared. The BIC values of the test implants were comparable and non-inferior over the time points studied, except for the 12 weeks time point which showed statistically significantly higher BIC values of the test (88.07 ± 5.35%) compared to the control implants (80.88 ± 7.51%) (p = .010). Similarly comparable and non-inferior were the fBIC values, except for the 6-week outcome, which showed statistically higher values for the test (-546.5 ± 450.80 μm) compared to the control implants (-75.7 ± 100.59 μm). fBIC results for the test implants were qualitatively more stable and consistent between test time points. Novel self-cutting bone-level test implants demonstrated superior osseointegration and similar bone levels compared to conventional bone-level implants after a healing period of 12 weeks in healed ridges.

Fixation technique of biodegradable magnesium alloy suture anchor in the rotator cuff repair of the shoulder in a goat model: a technical note

BackgroundShoulder disorders, particularly rotator cuff tears, are prevalent musculoskeletal conditions related to aging. Although the widely used suture anchor technique provides strong mechanical support to the tendon, it is associated with a risk of postoperative tendon retearing. The conventionally used titanium alloys can affect the interpretation of magnetic resonance imaging. Degradable magnesium alloys possess excellent biocompatibility, similar mechanical property to the bone, and stimulating bone formation ability from Mg2+. The purpose of this experiment was to develop innovative magnesium-based suture anchors to enhance rotator cuff repair by improving fixation materials, and to evaluate their feasibility in a goat model.MethodsWe developed fluoridized ZK60 suture anchors as the implantation material for two goats, who underwent rotator cuff repair surgery on both shoulders. Computed tomography (CT) and histological analysis were performed at 12 weeks postoperatively, and the results were compared between the magnesium and titanium alloy groups. Additionally, a hematological examination was conducted, which included assessments of red blood cells, white blood cells, platelets, coagulation function, liver function, kidney function, and magnesium ion concentration.ResultsThe 12-week postoperative CT images showed intact MgF2 ZK60 suture anchors, effectively reconnecting the infraspinatus tendon to the humeral head. The anchors became less visible on CT scans, indicating absorption by surrounding tissues. New bone formation in the MgF2 group surpassed that in the Ti group, demonstrating superior osseointegration. The similarity between cortical bone and magnesium reduced stress-shielding and promoted bone regeneration. Histological analysis revealed successful tendon healing with MgF2 anchors, while the Ti group showed discontinuous interfaces and reduced collagen secretion. Hematological examination showed stable liver, renal function, and magnesium ion levels.ConclusionsThe findings indicate that MgF2-coated suture anchors are feasible for rotator cuff repair and potentially other orthopedic applications. We hope that magnesium alloy anchors can become the solution for rotator cuff tendon repair surgery.

Morphological and biomechanical characterization of long bones and peri-implant bone repair in type 2 diabetic rats treated with resveratrol

Type 2 diabetes interferes with bone remodeling mechanisms, requiring studies to reverse this damage, and resveratrol is a polyphenol with rich properties. This study aimed to characterize the long bone morphology and peri-implant biomechanics of normoglycemic and type 2 diabetic animals treated with resveratrol. Thirty-two male Wistar rats were used and divided into normoglycemic and diabetic with or without treatment. They had the installation of implants in the tibia and treatment with oral resveratrol within 45 days. Resveratrol was responsible for weight homeostasis and decreased glycemic levels in rats with type 2 diabetes. The three-point bending testing, resveratrol showed positive effects on the biomechanics of long bones, corroborating a more resistant bone in comparison to untreated diabetics. Micro-ct revealed how bone metabolism is affected by systemic disease, decreasing bone quality. The counter-torque of normoglycemic animals showed superior osseointegration to diabetes, with no differences in the administration of the polyphenol, showing the sovereignty of the deleterious effects of the disease when there is a tissue lesion and an inflammatory picture installed. Overall, resveratrol acted positively in the etiopathogenesis of type 2 diabetes and revealed positive effects on the strength of long bones.

Influence of chitosan and Cissus quandrangularis coating on osseointegration in titanium implants in rabbits: A preclinical in vivo study

BackgroundTitanium (Ti) implants has been criticized for the tiring wait for osseointegration, often making the patient reconsider implant treatment. Surface treated Ti implants are emerging as a promising solution with superior osseointegration, early loading protocols and shortened period of edentulousness. The aim of this study is to assess the osseointegration of Ti surface coated with novel Cissus quandrangularis Chitosan Hydrogel (CqChH) compared to Commercially pure (Cp) implants. Methods24 Cp Ti implants were divided into 2 subgroups (n = 12). The test group consisted of Ti implants surface treated with the novel hydrogel and control group consisted of Cp Ti implants. 3 % CqChH was prepared and was coated on the Ti implants prior to placement in the femur and tibial heads of rabbits. Implant Stability Quotient (ISQ) was recorded at the 6th and 12th week. Animals were sacrificed and subjected to Removal Torque Quotient (RTQ). The samples were retrieved en bloc and stained for histopathologic analysis. The collected data was subjected to statistical analysis using Unpaired student t-Test. ResultsAt the end of 6th week CqChH coated implants did not show any statistically significant difference in both ISQ and RTQ values compared to Cp ones. However, at the end of the 12th week CqChH coated implants demonstrated significantly higher ISQ (73.91 ± 4.39) and RTQ (75.96 ± 14.10) compared to Cp ones. ConclusionsThis study demonstrated that the novel hydrogel coating applied to the implant's surface exhibited not only enhanced bone regeneration but also elicited a new bone formation.

A SiO2 layer on PEO-treated Mg for enhanced corrosion resistance and bone regeneration.

Magnesium (Mg) is a promising biodegradable metal for orthopedic applications, and plasma electrolytic oxidation (PEO) has been widely studied as a corrosion protection coating on Mg-based implants. However, the porous structures and easily formed cracks in fluid are disadvantageous for long-term corrosion protection. In this study, a SiO2 layer was deposited on PEO-treated Mg to inhibit the formation of cracks on the PEO layer and prevent the permeation of corrosive fluid. The SiO2 layer did not alter the surface morphology of the PEO layer but considerably enhanced its corrosion resistance. The in vitro culture of MC3T3-E1 cells demonstrated the good cytocompatibility and osteogenic induction ability of SiO2-coated PEO-treated Mg, which could be attributed to Mg and Si ions released from the coating. The coating also favored the angiogenesis behaviors of HUVEC. Furthermore, with the continuous release of Mg and Si ions, the as-prepared implant showed a superior osseointegration ability in a rat bone implantation model. In summary, this newly designed Mg-based implant shows promising potential for orthopedic applications.

Endplate volumetric bone mineral density biomechanically matched interbody cage.

Disc degenerative problems affect the aging population, globally, and interbody fusion is a crucial surgical treatment. The interbody cage is the critical implant in interbody fusion surgery; however, its subsidence risk becomes a remarkable clinical complication. Cage subsidence is caused due to a mismatch of material properties between the bone and implant, specifically, the higher elastic modulus of the cage relative to that of the spinal segments, inducing subsidence. Our recent observation has demonstrated that endplate volumetric bone mineral density (EP-vBMD) measured through the greatest cortex-occupied 1.25-mm height region of interest, using automatic phantomless quantitative computed tomography scanning, could be an independent cage subsidence predictor and a tool for cage selection instruction. Porous design on the metallic cage is a trend in interbody fusion devices as it provides a solution to the subsidence problem. Moreover, the superior osseointegration effect of the metallic cage, like the titanium alloy cage, is retained. Patient-specific customization of porous metallic cages based on the greatest subsidence-related EP-vBMD may be a good modification for the cage design as it can achieve biomechanical matching with the contacting bone tissue. We proposed a novel perspective on porous metallic cages by customizing the elastic modulus of porous metallic cages by modifying its porosity according to endplate elastic modulus calculated from EP-vBMD. A three-grade porosity customization strategy was introduced, and direct porosity-modulus customization was also available depending on the patient's or doctor's discretion.

Benchmark performance of anodized vs. sandblasted implant surfaces in an acute dehiscence type defect animal model.

Crestal bone formation represents a crucial aspect of the esthetic and biological success of dental implants. This controlled preclinical study analyzed the effect of implant surface and implant geometry on de novo crestal bone formation and osseointegration. Histological and histomorphometrical analysis was performed to compare three implant groups, that is, (1) a novel, commercially available, gradient anodized implant, (2) a custom-made geometric replica of implant "1," displaying a superhydrophilic micro-rough large-grit sandblasted and acid-etched surface, and (3) a commercially available implant, having the same surface as "2" but a different implant geometry. The study applied a standardized buccal acute-type dehiscence model in minipigs with observation periods of 2 and 8 weeks of healing. The amount of newly formed crestal bone (BATA) around control groups (2) and (3) was significantly increased when compared to the test group (1) at the 8 weeks of healing time point. Similar results were obtained for all parameters related to osseointegration and direct bone apposition, to the implant surface (dBIC, VBC, and fBIC), demonstrating superior osseointegration of the moderately rough, compared to the gradient anodized functionalization. After 2 weeks, the osseointegration (nBIC) was found to be influenced by implant geometry with group (3) outperforming groups (1) and (2) on this parameter. At 8 weeks, nBIC was significantly higher for groups (2) and (3) compared to (1). The extent (BATA) of de novo crestal bone formation in the acute-type dehiscence defects was primarily influenced by implant surface characteristics and their ability to promote osseointegration and direct bone apposition. Osseointegration (nBIC) of the apical part was found to be influenced by a combination of surface characteristics and implant geometry. For early healing, implant geometry may have a more pronounced effect on facilitating osseointegration, relative to the specific surface characteristics.

Mussel-inspired dopamine-CuII coated polyetheretherketone surface with direct and immunomodulatory effect to facilitate osteogenesis, angiogenesis, and antibacterial ability

Implant-associated infection (IAI) and insufficient implant osseointegration are two primary concerns of implant failure. Polyetheretherketone (PEEK), though widely used in orthopedic implants, has been limited in clinical applications by its poor osteogenic activity, inferior antibacterial ability, and improper immunological reactions. In this study, copper (Cu), a multi-functional bioactive ion, is incorporated into the polydopamine (PDA) coating on PEEK surfaces using a metal-catecholamine assembling strategy. This DA-CuII coating induces a spatial distribution of Cu, exerting biological functions simultaneously through passive contact and active release of Cu. DA-CuII coated PEEK surfaces exhibit not only superior abilities of osteogenesis, angiogenesis, and antibiosis but also possess immunomodulatory effects to enhance macrophages-mediated osteogenesis and antibacterial activity. Moreover, the DA-CuII coated PEEK induces a mild and necessary inflammatory response, exhibiting excellent antibacterial ability and superior osseointegration. Our findings suggest that DA-CuII coated PEEK has excellent potential for orthopedic implants and provides new insight into novel modification strategies of PEEK materials.

Construction of Local Drug Delivery System on Titanium-Based Implants to Improve Osseointegration.

Titanium and its alloys are the most widely applied orthopedic and dental implant materials due to their high biocompatibility, superior corrosion resistance, and outstanding mechanical properties. However, the lack of superior osseointegration remains the main obstacle to successful implantation. Previous traditional surface modification methods of titanium-based implants cannot fully meet the clinical needs of osseointegration. The construction of local drug delivery systems (e.g., antimicrobial drug delivery systems, anti-bone resorption drug delivery systems, etc.) on titanium-based implants has been proved to be an effective strategy to improve osseointegration. Meanwhile, these drug delivery systems can also be combined with traditional surface modification methods, such as anodic oxidation, acid etching, surface coating technology, etc., to achieve desirable and enhanced osseointegration. In this paper, we review the research progress of different local drug delivery systems using titanium-based implants and provide a theoretical basis for further research on drug delivery systems to promote bone–implant integration in the future.

Aspirin/PLGA coated 3D-printed Ti-6Al-4V alloy modulate macrophage polarization to enhance osteoblast differentiation and osseointegration

Although titanium (Ti) and Ti-based alloy have been widely used as dental and orthopedic implant materials, its bioinertness hindered the rapid osseointegration. Therefore, it is recommended to acquire ideal topographic and chemical characteristics through surface modification methods. 3D printing is a delicate manufacture technique which possesses superior controllability and reproducibility. While aspirin serve as a well-established non-steroidal anti-inflammatory agent. Recently, the importance of immune system in regulating bone dynamics has attracted increasing attention. We herein superimposed the aspirin/poly (lactic–co–glycolic acid) (ASP/PLGA) coating on the 3D-printed Ti-6Al-4V surface with uniform micro-structure to establish the Ti64-M-ASP/PLGA substrate. Scanning electron microscopy (SEM), x-ray photoelectron spectroscopy (XPS) and contact angle test confirmed the successful fabrication of the Ti64-M-ASP/PLGA substrate, with increased wettability and sustained release pattern of ASP. Compared with the Ti64 base material, the Ti64-M-ASP/PLGA substrate showed enhanced M2 and depressed M1 genes and proteins expressions in macrophages. The novel Ti64-M-ASP/PLGA substrate also displayed enhanced osteoblast proliferation, adhesion, extracellular mineralization ability and osteogenic gene expressions when cultured with macrophage conditioned medium in vitro. Furthermore, rat femora implantation model was used for in vivo evaluation. After 4 weeks of implantation, push out test, micro-computed tomography (micro-CT) and histological analyses all confirmed the superior osseointegration capabilities of the Ti64-M-ASP/PLGA implant than the other groups. Our study revealed the synergistic role played by 3D-printed micro topography and immunoregulatory drug aspirin in promoting osteogenesis in vitro and accelerating osseointegration in vivo, thus providing a promising method for better modifying the implant surface.Graphical abstract

Magnesium cationic cue enriched interfacial tissue microenvironment nurtures the osseointegration of gamma-irradiated allograft bone

Regardless of the advancement of synthetic bone substitutes, allograft-derived bone substitutes still dominate in the orthopaedic circle in the treatments of bone diseases. Nevertheless, the stringent devitalization process jeopardizes their osseointegration with host bone and therefore prone to long-term failure. Hence, improving osseointegration and transplantation efficiency remains important. The alteration of bone tissue microenvironment (TME) to facilitate osseointegration has been generally recognized. However, the concept of exerting metal ionic cue in bone TME without compromising the mechanical properties of bone allograft is challenging. To address this concern, an interfacial tissue microenvironment with magnesium cationc cue was tailored onto the gamma-irradiated allograft bone using a customized magnesium-plasma surface treatment. The formation of the Mg cationic cue enriched interfacial tissue microenvironment on allograft bone was verified by the scanning ion-selective electrode technique. The cellular activities of human TERT-immortalized mesenchymal stem cells on the Mg-enriched grafts were notably upregulated. In the animal test, superior osseointegration between Mg-enriched graft and host bone was found, whereas poor integration was observed in the gamma-irradiated controls at 28 days post-operation. Furthermore, the bony in-growth appeared on magnesium-enriched allograft bone was significant higher. The mechanism possibly correlates to the up-regulation of integrin receptors in mesenchymal stem cells under modified bone TME that directly orchestrate the initial cell attachment and osteogenic differentiation of mesenchymal stem cells. Lastly, our findings demonstrate the significance of magnesium cation modified bone allograft that can potentially translate to various orthopaedic procedures requiring bone augmentation.

Strontium-Loaded Nanotubes of Ti-24Nb-4Zr-8Sn Alloys for Biomedical Implantation.

Ti-24Nb-4Zr-8Sn (Ti2448) alloys, with a relatively low elastic modulus and unique mechanical properties, are desirable materials for oral implantation. In the current study, a multifaceted strontium-incorporating nanotube coating was fabricated on a Ti2448 alloy (Ti2-NTSr) through anodization and hydrothermal procedures. In vitro, the Ti2-NTSr specimens demonstrated better osteogenic properties and more favorable osteoimmunomodulatory abilities. Moreover, macrophages on Ti2-NTSr specimens could improve the recruitment and osteogenic differentiation of osteoblasts. In vivo, dense clots with highly branched, thin fibrins and small pores existed on the Ti2-NTSr implant in the early stage after surgery. Analysis of the deposition of Ca and P elements, hard tissue slices and the bone-implant contact rate (BIC%) of the Ti2-NTSr implants also showed superior osseointegration. Taken together, these results demonstrate that the Ti2-NTSr coating may maximize the clinical outcomes of Ti2448 alloys for implantation applications.

Fabrication of a bio-instructive scaffold conferred with a favorable microenvironment allowing for superior implant osseointegration and accelerated in situ vascularized bone regeneration via type H vessel formation

The potential translation of bio-inert polymer scaffolds as bone substitutes is limited by the lack of neovascularization upon implantation and subsequently diminished ingrowth of host bone, most likely resulted from the inability to replicate appropriate endogenous crosstalk between cells. Human umbilical vein endothelial cell-derived decellularized extracellular matrix (HdECM), which contains a collection of angiocrine biomolecules, has recently been demonstrated to mediate endothelial cells(ECs) – osteoprogenitors(OPs) crosstalk. We employed the HdECM to create a PCL (polycaprolactone)/fibrin/HdECM (PFE) hybrid scaffold. We hypothesized PFE scaffold could reconstitute a bio-instructive microenvironment that reintroduces the crosstalk, resulting in vascularized bone regeneration. Following implantation in a rat femoral bone defect, the PFE scaffold demonstrated early vascular infiltration and enhanced bone regeneration by microangiography (μ-AG) and micro-computational tomography (μ-CT). Based on the immunofluorescence studies, PFE mediated the endogenous angiogenesis and osteogenesis with a substantial number of type H vessels and osteoprogenitors. In addition, superior osseointegration was observed by a direct host bone-PCL interface, which was likely attributed to the formation of type H vessels. The bio-instructive microenvironment created by our innovative PFE scaffold made possible superior osseointegration and type H vessel-related bone regeneration. It could become an alternative solution of improving the osseointegration of bone substitutes with the help of induced type H vessels, which could compensate for the inherent biological inertness of synthetic polymers.

Dual-functional polyetheretherketone surface modification for regulating immunity and bone metabolism

Polyetheretherketone (PEEK) has gained increased attention as an orthopedic implant material in recent years. However, the adverse inflammatory and immunological reactions elicited by the PEEK surface result in inferior osteointegration and affect its clinical utility. To improve osseointegration and enhance the success rate of PEEK implants, the surface can be biofunctionalized to be immunomodulatory. Herein, A-485, a potent and selective catalytic inhibitor of p300/CBP, was loaded into mesoporous bioactive glass that had been immobilized on the PEEK surface, and the immunomodulatory capability and effects of the biofunctionalized PEEK implants on osteointegration were evaluated. In vitro, the biofunctionalized PEEK surface not only suppressed the acute inflammatory response of macrophages, but also inhibited bone resorption and promoted osteogenesis, indicating that it plays critical and complex roles in maintaining normal bone metabolism. Moreover, the biofunctionalized surface induced less fibrous capsule formation and exhibited superior osseointegration properties in vivo. The A-485-loaded MBG-biofunctionalized PEEK surface attenuated inappropriately activated immune responses mediated by macrophages and subsequently inhibited osteoclastogenesis, promoting osteogenesis and yielding superior osseointegration. Therefore, these surface-biofunctionalized PEEK implants, which regulate both immunity and bone metabolism, demonstrate strong potential for clinical application as orthopedic implants.

Layered Double Hydroxide Modified Bone Cement Promoting Osseointegration via Multiple Osteogenic Signal Pathways.

Poly(methyl methacrylate) (PMMA) bone cement has been widely used in orthopedic surgeries including total hip/knee replacement, vertebral compression fracture treatment, and bone defect filling. However, aseptic loosening of the interface between PMMA bone cement and bone often leads to failure. Hence, the development of modified PMMA that facilitates the growth of bone into the modified PMMA bone cement is key to reducing the incidence of aseptic loosening. In this study, MgAl-layered double hydroxide (LDH) microsheets modified PMMA (PMMA&LDH) bone cement with superior osseointegration performance has been synthesized. The maximum polymerization reaction temperature of PMMA&LDH decreased by 7.0 and 11.8 °C, respectively, compared with that of PMMA and PMMA&COL-I (mineralized collagen I modified PMMA). The mechanical performance of PMMA&LDH decreased slightly in comparison with PMMA, which is beneficial to alleviate stress-shielding osteolysis, and indirectly promote osseointegration. The superior osteogenic ability of PMMA&LDH has been demonstrated in vivo, which boosts bone growth by 2.17- and 18.34-fold increments compared to the PMMA&COL-I and PMMA groups at 2 months, postoperatively. Moreover, transcriptome sequencing revealed four key osteogenic pathways: p38 MAPK, ERK/MAPK, FGF, and TGF-β, which were further confirmed by IPA, qPCR, and Western blot assays. Hence, LDH-modified PMMA bone cement is a promising biomaterial to enhance bone growth with potential applications in relevant orthopedic surgeries.

Osseointegration of Hafnium when Compared to Titanium - A Structured Review

Aim: This systematic review was conducted to analyse osseointegration of hafnium over conventional titanium. Materials and Methods: Search methodology was comprehended using PICO analysis and a comprehensive search was initiated in PubMed Central, Medline, Cochrane, Ovid, Science Direct, Copernicus and Google Scholar databases to identify the related literature. Randomised control trials, clinical studies, case control studies and animal studies were searched for osseointegration of hafnium coated titanium implants versus conventional titanium implants. Timeline was set to include all the manuscripts published till December 2018 in this review. Clinical Significance: Hafnium is a very promising surface coating intervention that can augment osseointegration in titanium implants. If research could be widened, including in vivo studies on hafnium as a metal for coating over dental implants or as a dental implant material itself to enhance better osseointegration, it could explore possibilities of this metal in the rehabilitation of both intra and extra oral defects and in medically compromised patients with poor quality of bone. Results: Out of the 25 articles obtained from the PICO based keyword search, 5 studies were excluded based on title and abstract. Out of the remaining 20 studies, 16 were excluded based on the inclusion and exclusion criteria of our interest and finally, 4 were included on the basis of core data. Conclusion: This systematic review observed hafnium metal exhibited superior osseointegration than titanium. Owing to its biocompatibility, hafnium could be an alternative to titanium, in the near future.