Ti Implants Research Articles

Light-sensitive PEG hydrogel with antibacterial performance for pacemaker pocket infection prevention

Prevention of cardiovascular implantable electronic devices (CIED) infection is crucial for successful outcomes. In this study, we report an adhesive and antibacterial hydrogel coating for CIED infection treatment, by immobilizing polyethylene glycol (PEG) and 2′-O-hydroxypropyl trimethyl ammonium chloride chitosan (HAC) on Ti surface. Initial alkali and APTES treatment caused the formation of –NH2 to enhance the adhesion of the hydrogel coating to Ti implants, followed by immobilizing a photo-cross-linkable PEG/2′-O-HTACCS hydrogel on Ti/OH/NH2 surface. Surface characterization of Ti/OH/NH2 sample and adhesion testing of hydrogel on Ti/OH/NH2 surface confirm successful immobilization of hydrogel onto the Ti/OH/NH2 surface. In vitro and in vivo antimicrobial results exhibited that the photo-cross-linkable PEG/HAC composite hydrogel has excellent antimicrobial capabilities against both Grampositive (S. aureus and S. epidermidis) and Gram-negative (P. aeruginosa and E. coli) bacteria. The outcome of this study demonstrates the photo-cross linked PEG/HAC coating hydrogels can be easily formed on the Ti implants, and has great potential in preventing CIED pocket infection.

A Multifunctional Metal-Phenolic Nanocoating on Bone Implants for Enhanced Osseointegration via Early Immunomodulation.

Surface modification is an important approach to improve osseointegration of the endosseous implants, however it is still desirable to develop a facile yet efficient coating strategy. Herein, a metal-phenolic network (MPN) is proposed as a multifunctional nanocoating on titanium (Ti) implants for enhanced osseointegration through early immunomodulation. With tannic acid (TA) and Sr2+ self-assembled on Ti substrates, the MPN coatings provided a bioactive interface, which can facilitate the initial adhesion and recruitment of bone marrow mesenchymal stem cells (BMSCs) and polarize macrophage toward M2 phenotype. Furthermore, the TA-Sr coatings accelerated the osteogenic differentiation of BMSCs. In vivo evaluations further confirmed the enhanced osseointegration of TA-Sr modified implants via generating a favorable osteoimmune microenvironment. In general, these results suggest that TA-Sr MPN nanocoating is a promising strategy for achieving better and faster osseointegration of bone implants, which can be easily utilized in future clinical applications.

Multifunctional Prosthesis Surface: Modification of Titanium with Cinnamaldehyde-Loaded Hierarchical Titanium Dioxide Nanotubes.

Orthopedic prostheses are the ultimate therapeutic solution for various end-stage orthopedic conditions. However, aseptic loosening and pyogenic infections remain as primary complications associated with these devices. In this study, a hierarchical titanium dioxide (TiO2) nanotube drug delivery system loaded with cinnamaldehyde for the surface modification of titanium implants, is constructed. These specially designed dual-layer TiO2 nanotubes enhance material reactivity and provide an extensive drug-loading platform within a short time. The introduction of cinnamaldehyde enhances the bone integration performance of the scaffold (simultaneously promoting bone formation and inhibiting bone resorption), anti-inflammatory capacity, and antibacterial properties. In vitro experiments have demonstrated that this system promoted osteogenesis by upregulating both Wnt/β-catenin and MAPK signaling pathways. Furthermore, it inhibits osteoclast formation, suppresses macrophage-mediated inflammatory responses, and impedes the proliferation of Staphylococcus aureus and Escherichia coli. In vivo experiments shows that this material enhances bone integration in a rat model of femoral defects. In addition, it effectively enhances the antibacterial and anti-inflammatory properties in a subcutaneous implant in a rat model. This study provides a straightforward and highly effective surface modification strategy for orthopedic Ti implants.

2D magnesium phosphate resorbable coating to enhance cell adhesion on titanium surfaces

Titanium and its alloys are essential metals for orthopedic implant manufacturing due to their exceptional mechanical properties and biocompatibility, used extensively for treating various orthopedic conditions. However, Titanium (Ti) implants have a disadvantage due to lack of bioactivity, potentially affecting osseointegration and osteoconductive capabilities, and may take several months to integrate with bone tissue. In this work, we prepared a layer of 2D magnesium phosphate (MgPi) coating on the surface of titanium surfaces via the spin-coating technique. Various techniques were used to study the phase composition of the coatings, including FTIR, Raman spectroscopy, NMR, and XRD analysis. Morphology and chemical analysis were performed using Atomic force microscopy and SEM/EDX. Nano-scratch test and water contact angle measurements were used to measure adhesion strength and wettability. In addition, in vitro cell assays were used to assess cell adhesion and viability to determine how the MC3T3-E1 osteoblast-like cells reacted to the different treated Ti substrates. AFM results showed that the surface roughness became lower after coatings. MgPi-coated samples showed higher hydrophilicity, protein adsorption, and cell viability than uncoated samples. The nano-scratch test showed that the MgPi coating showed better adherence to chemically and thermally treated samples compared to untreated samples. The deposited MgPi coating has good adhesion to the Ti-substrates. Most significantly, compared to uncoated control (Ti) (p < 0.005) and chemically treated coated samples CT-MgPi (p < 0.005), MC3T3-E1 cell proliferation was significantly increased on thermochemical coated surfaces. These findings point to resorbable two-dimensional MgPi coatings as a potential candidate for promoting Ti implant osseointegration.

Aseptic Silk Ligatures Induce Bone Resorption Around Titanium Implants: A 12-Week Pilot Study in Rabbits.

Marginal bone resorption (MBR) around dental implants may sometimes be a self-limiting condition due to balancing immunologic reactions against utilized materials rather than a progressive bacterial infection. Contrary to previous assumptions from ligature-induced experimental peri-implantitis studies, a recent 8-week experiment by the present authors showed that marginal ligatures trigger an inflammatory immune response, resulting in bone resorption around implants in the absence of plaque. The present study aimed to investigate whether this inflammatory/immunologic reaction attenuates or progresses toward implant failure after a longer healing time (12 weeks). Sterile silk ligatures were placed around the top of titanium (Ti) implants and compressed against the femoral cortical bone plate of six rabbits. A nonligated implant was used as a control. After 12 weeks of submerged healing, ground sections of implants and surrounding tissues were investigated with light microscopy. The marginal soft tissues were also analyzed using selected quantitative polymerase chain reaction (qPCR) markers. Histologically, the ligatures were outlined by immune cells, including multinucleated giant cells (MNGCs), with adjacent fibrous encapsulation and resorbed peripheral bone that contrasted from the osseointegrated nonligated control implants. The difference in expression of qPCR markers was not significant, but > two-fold upregulation of markers CD11b, IL1β, ARG1, NCF1, and CD4 and > twofold downregulation of CD8 indicated a mild, focal inflammatory/immune response against the ligatures compared to controls, with upregulation of M1 and M2 macrophages, neutrophils, and helper T-cells as well as downregulation of killer T cells. Further, the bone formation markers OC and ALPL were > two-fold downregulated (consistent with the lack of osseointegration of the ligatures) compared to control implants. Marginal silk ligatures trigger an inflammatory/immune response and aseptic bone resorption around implants. Compared to the previous 8-week study, the inflammatory reaction against the silk appears to attenuate with time, with only a mild persisting inflammation that may block osseointegration; instead, a fibrous tissue encapsulation-type reaction is maintained. This may explain why traditional ligature experiments have required regular exchange of ligatures for the bone resorption to progress.

Enhancing immune modulation and bone regeneration on titanium implants by alleviating the hypoxic microenvironment and releasing bioactive ions

Bone implantation inevitably causes damage to surrounding vasculature, resulting in a hypoxic microenvironment that hinders bone regeneration. Although titanium (Ti)-based devices are widely used as bone implants, their inherent bioinert surface leads to poor osteointegration. Herein, a strontium peroxide (SrO2)-decorated Ti implant, Ti_P@SrO2, was constructed through coating with poly-L-lactic acid (PLLA) to alleviate the hypoxic microenvironment and transform the bioinert surface of the implant into a bioactive surface. PLLA degradation resulted in an acidic microenvironment and the release of SrO2 nanoparticles. The acidic microenvironment then accelerated the decomposition of SrO2, resulting in the release of O2 and Sr ions. O2 released from Ti_P@SrO2 can alleviate the hypoxic microenvironment, thus enhancing cell proliferation in an O2-insufficient microenvironment. Furthermore, under hypoxic and normal microenvironments, Ti_P@SrO2 enhanced alkaline phosphatase activity and bone-related gene expression in C3H10T1/2 cells with the continuous release of Sr ions. Meanwhile, Ti_P@SrO2 suppressed M1 polarization and promoted M2 polarization of bone marrow-derived monocytes under hypoxic and normal conditions. Furthermore, in a rat implantation model, the implant enhanced new bone formation and improved osteointegration after modification with SrO2. In summary, the newly designed O2- and Sr ion-releasing Ti implants are promising for applications in bone defects.

Extracellular Vesicle Clicking on Osteoimplants Through Biomimetic Molecular Adhesion Enables Immune‐Enhanced Osseointegration in Diabetics

AbstractExtracellular vesicles (EVs) derived from differentiating induced stem cells maintain their original stemness and differentiating trends and possess strong immunoregulatory capability. Biomaterials equipped with EVs are very promising in regenerative medicine. However, surface EV‐decoration on osteoimplants remains a challenge, due to the complexity of traditional molecular conjugations and the fragility of EVs. Here, mussel‐like molecular adhesion is combined with bioorthogonal click conjugation to introduce EVs on titanium (Ti) implants. The biomimetic adhesion and clickable molecular linkage allow mild and stable tethering of pre‐osteogenic mesenchymal stem cell (MSC)‐derived EVs on Ti implants. EV‐decorated implants exhibit significantly enhanced osseointegration on the bone‐implant surface under diabetic conditions, promoting increased expression of osteogenic genes. Modified surfaces impelled phenotypic alterations in macrophage polarization via multi‐pathway regulation, decreasing proinflammatory M1 macrophage formation, which can lead to the promotion of surface osteogenesis. On Ti rods implanted in a diabetic rat model, EV coating inhibited M1macrophages around the prosthesis, resulting in satisfactory long‐term osseointegration. This study offers a new perspective to represent a simple and effective means for surface EV decoration, providing an osteoimmunomodulatory effect to enhance the diabetic osseointegration of implants.

Hydrophobic Coating Platforms for High‐Efficiency Loading and Direct Transmembrane Delivery of Fat‐Soluble Osteogenic Drug for Enhanced Osseointegration of Titanium Implants

AbstractCompared with water‐soluble osteogenic drugs, fat‐soluble osteogenic drugs exhibit higher bioavailability and drug stability, making them valuable for enhancing the osseointegration of implants. However, existing drug‐loading coatings are primarily designed for water‐soluble drugs, limiting their effectiveness in loading and delivering fat‐soluble osteogenic drugs. This study employed alkali treatment, silanization, and oleic acid acylation to sequentially modify the surface of Ti alloy, aiming to fabricate surfaces capable of efficiently loading and delivering fat‐soluble osteogenic drugs. Results show that the hydrophilicity and loading capacity of fat‐soluble osteogenic drugs strongly depended on the duration of the acylation treatment. Furthermore, the drug release mechanism involved direct diffusion from the coating to the cells in contact, resulting in improved bioavailability, as opposed to diffusion into the surrounding medium and subsequent cellular uptake. In vitro experiments using vitamine D3 (VD3) as a model drug confirmed that the coating effectively promoted bone formation through the highly efficient delivery of VD3. Furthermore, in vivo experiments demonstrated that the VD3‐loaded lipophilic surface significantly enhanced osteogenic capability and improved the osseointegration of titanium implants. This study provides a promising strategy for loading fat‐soluble drugs onto Ti implants and direct experimental evidence demonstrating the significant value of fat‐soluble drugs in promoting implant osseointegration.

Electrophoretic deposition of photothermal responsive antibacterial coatings on titanium with controlled release of silver ions

Burst release of antibacterial agents generated by the surface antibacterial modification of Ti implants frequently results in a reduction in their biocompatibility and substantial toxic side effects. In this study, core-shelled nanoparticles namely AgNR@MSN, were synthesized successfully by mesoporous silica shell in-situ encapsulated Ag nanorods, and then co-deposited with chitosan to form a AgNR@MSN-chitosan composite coating on Ti substrate by electrophoretic deposition. The developed composite coating, due to the presence of AgNR, presented excellent photothermal effect under the irradiation of an 808 nm near-infrared laser, leading to both rapid increase of local temperature and triggered release of Ag ions for bacterial-killing effect against both E. coli and S. aureus. The addition of AgNR@MSN also improved the wettability of the coating and the MSN shell with mesoporous tunnels could barrier the contact and release rate of Ag to improve the biocompatibility. The developed photothermal responsive coating could be considered as a promising platform for achieving controlled release of Ag ions with outstanding antibacterial and biocompatible properties.

Additively Manufactured SiO2 and Cu-Added Ti Implants for Synergistic Enhancement of Bone Formation and Antibacterial Efficacy.

Commercially pure titanium (CpTi), a bioinert metal, is used as an implant material at low load-bearing sites and as a porous coating on Ti6Al4V at high load-bearing sites. There is an unmet need for metallic biomaterials to improve osseointegration and inherent antimicrobial resistance. In this study, we have added 1 wt % SiO2 and 3 wt % Cu to the CpTi matrix and processed via metal additive manufacturing (AM). Si4+ ions promote angiogenesis and osteogenesis. CpTi-SiO2 composition exhibited 4.5 times higher bone formation at the bone-implant interface over CpTi in an in vivo study with a rat distal femur model. In vitro bacterial studies with Gram-positive Staphylococcus aureus bacterium revealed 85% antibacterial efficacy by CpTi-SiO2-3Cu than CpTi. CpTi-SiO2-3Cu did not show any inflammatory markers in vivo, indicating the absence of cytotoxicity, but displayed delayed osseointegration compared to CpTi-SiO2. CpTi-SiO2-3Cu displayed 3-fold higher mineralized bone formation than CpTi. Our results emphasize the synergistic effect of SiO2 and Cu addition in CpTi, promoting enhanced early stage osseointegration and inherent antibacterial efficacy, contributing toward implant longevity and stability in vivo.

Citric acid fine-tuned silk fibroin/silver nanocomposite coating affords biomimetic, infection-defensive and pro-healing/osteo-angiogenic microenvironments for functional implant osseointegration

Prosthesis implant failures owing to recalcitrant bacterial infections and unsatisfactory biointegration remains a formidable challenge in orthopedic clinics. A fascinating solution is to develop advanced coating-functionalized implants to confer infection-free and pro-healing/osteo-angiogenic microenvironments amiable for establishing functional osteointegration. Inspired by the bone ECM-mimicking silk fibroin (SF) and the metabonegenic role of natural citrate in bone, herein we designed antimicrobial (nanosilver)-loaded, SF/citric acid (CA)-based biomimetic composite coatings (CA@Ag/SF) to furnish bioinert titanium with the abovementioned multifunctionalities. The key regards the ingenious synthesis of the CA@Ag/SF coating precursor by taking CA as a template/regulator for AgNPs nucleation and growth. Specifically, the reductive, metal-chelating functional groups of CA were leveraged to bind and reduce Ag+, while decorating and stabilizing the resulting AgNPs, thus producing uniform and monodispersed nanoparticles capped with CA “coronas” (CA@Ag). More attractively, the inclusion of CA into the Ag/SF system was found to also fine-tune the resultant coatings’ surface topography and chemistry and Ag+-delivering behaviors, while conferring improved yet well-balanced antibacterial properties, osteocompatibility, and osteo/angiogenic functionalities that were unattainable in an Ag/SF control coating. Furthermore, in vivo implantation in rat femoral-condyle defects demonstrated that Ti implants decorated with CA@Ag/SF elicited drastically enhanced bone regeneration and rapid yet tight osseointegration, signifying great potential for clinical application. Our study has great potential for applications in harnessing CA and derivatives to optimize the performances of orthopedic biomaterials.

Influence of surface topographic morphologies and nanoparticle incorporation on surface properties of pure Ti implants for oral applications

One common problem in using titanium (Ti) dental implants is peri-implantitis. To prevent peri-implantitis on Ti implants in an oral environment, we introduced novel topographic microstructures onto the surfaces of pure Ti implants via sandblasting, acid etching, and hydrothermal treatment before adding ZnO nanocomposite coatings and TiO2 nanocomposite coatings via magnetron sputtering. We comprehensively investigated the influence of surface topographic morphologies and elemental composition of coatings on the physicochemical properties and antibacterial efficacy of the specimens. Our results indicate that the novel topographic surfaces and magnetron sputtered coatings both exhibit good cytocompatibility. Our results also suggest that coating composition, rather than surface topographic morphology, is the primary factor influencing the antibacterial performance of Ti implants. Therefore, the magnetron sputtering of ZnO and TiO2 coatings onto surfaces can be an effective technique for improving the antibacterial properties of Ti implants for oral applications.

Blood-derived products can moderate the activity of neutrophils isolated after biomaterial implantation in a sheep model

Neutrophils play a pivotal role in both the inflammatory phase and subsequent repair processes, making their activity crucial after contact with biomaterials. Excessive neutrophil activation can lead to complications, including implant rejection, highlighting the importance of modulating their activity. This study investigates the long-term interaction of circulating ovine neutrophils with titanium (Ti) and silicon-doped layer (Si-DLC) coated implants. Additionally, the effects of platelet-rich plasma (PRP), platelet-poor plasma (PPP), and antimicrobial neutrophil crude extract (ANE) on neutrophil activity were assessed. Twelve female sheep were divided into Ti, Si-DLC implant and a control group. Neutrophils were stimulated with PRP, PPP, ovine ANE (oANE), or rabbit ANE (rANE), and their enzymatic activity and reactive oxygen and nitrogen species (RONS) generation were evaluated. Hematological parameters were also analyzed. Results showed no adverse effects at implant sites, and all hematological parameters remained within reference values. Ti and Si-DLC implants did not alter neutrophil activity. PRP significantly increased neutrophil activity and RONS production, while PPP decreased activity. oANE reduced enzymatic activity and RONS generation, indicating potential antiinflammatory effects. rANE showed varied effects on neutrophil function. Both ANEs lacked antimicrobial activity against tested pathogens. This study demonstrates the hemocompatibility of Ti and Si-DLC implants and highlights the potential of blood-derived products in modulating the inflammatory response to implants.

Cu2-xS homojunction coatings empower titanium implants with near-infrared-triggered antibacterial and antifouling properties.

For decades, implant-associated infections (IAIs) caused by pathogenic bacteria have been associated with high failure and mortality rates in implantation surgeries, posing a serious threat to global public health. Therefore, developing a functionalized biomaterial coating with anti-fouling and anti-bacterial functions is crucial for alleviating implant infections. Herein, a near-infrared-responsive anti-bacterial and anti-adhesive coating (Ti-PEG-Cu2-xS) constructed on the surface of titanium (Ti) implants is reported. This coating is composed of nano-Cu2-xS with anti-bacterial activity and super-hydrophilic polyethylene glycol (PEG). Under near-infrared irradiation, the nano-catalyst Cu2-xS on the surface of Ti-PEG-Cu2-xS induces bacterial death by catalyzing the production of singlet oxygen (1O2). The Ti-PEG-Cu2-xS coating can effectively prevent bacterial adhesion and biofilm formation. This coating combines the antibacterial mechanisms of "active attack" and "passive defense", which can kill bacteria and inhibit biofilm formation. The results of in vitro and in vivo experiments have shown that Ti-PEG-Cu2-xS exhibits excellent anti-bacterial properties under near-infrared irradiation and can effectively prevent implant-related infections caused by Escherichia coli (E. coli) ATCC 8739 and Staphylococcus aureus (S. aureus). The antibacterial efficiency of Ti-PEG-Cu2-xS coatings against E. coli was 99.96% ± 0.058% and that of S. aureus was 99.66% ± 0.26%, respectively. In addition, the Ti-PEG-Cu2-xS coating has good blood compatibility and excellent bactericidal ability. Therefore, this multifunctional coating combines a non-adhesive surface strategy and a near-infrared phototherapy sterilization method, effectively blocking the initial attachment and proliferation of bacteria on implants via photothermal/photodynamic effects and providing a promising method for preventing bacterium-induced IAIs.

Titanium micro-nano textured surface with strontium incorporation improves osseointegration: an in vivo and in vitro study.

This study aimed to investigate the osseointegration of titanium (Ti) implants with micro-nano textured surfaces functionalized with strontium additions (Sr) in a pre-clinical rat tibia model. Ti commercially pure (cp-Ti) implants were installed bilaterally in the tibia of 64 Holtzman rats, divided into four experimental groups (n=16/group): (1) Machined surface - control (C); (2) Micro-nano textured surface treatment (MN); (3) Micro-nano textured surface with Sr2+ addition (MNSr); and (4) Micro-nano textured surface with a higher complementary addition of Sr2+ (MNSr+). In total, two experimental euthanasia periods were assessed at 15 and 45 days (n=8/period). The tibia was subjected to micro-computed tomography (μ-CT), histomorphometry with the EXAKT system, removal torque (TR) testing, and gene expression analysis by PCR-Array of 84 osteogenic markers. Gene expression and protein production of bone markers were performed in an in vitro model with MC3T3-E1 cells. The surface characteristics of the implants were evaluated by scanning electron microscopy (SEM), energy-dispersive spectroscopy (EDS), and laser scanning confocal microscopy. SEM, confocal, and EDS analyses demonstrated the formation of uniform micro-nano textured surfaces in the MN group and Sr addition in the MNSr and MNSr+ groups. TR test indicated greater osseointegration in the 45-day period for treated surfaces. Histological analysis highlighted the benefits of the treatments, especially in cortical bone, in which an increase in bone-implant contact was found in groups MN (15 days) and MNSr (45 days) compared to the control group. Gene expression analysis of osteogenic activity markers showed modulation of various osteogenesis-related genes. According to the in vitro model, RT-qPCR and ELISA demonstrated that the treatments favored gene expression and production of osteoblastic differentiation markers. Micro-nano textured surface and Sr addition can effectively improve and accelerate implant osseointegration and is, therefore, an attractive approach to modifying titanium implant surfaces with significant potential in clinical practice.

Combining sandblasting and pink anodisation of Ti implants as a promising method for improving fibroblast adhesion and immune response.

This study examined the effect of combining the sandblasting and anodising of titanium alloys used in implants on the cell response and protein adsorption patterns. The titanium samples were divided into four groups depending on the surface treatment: machining (MC), pink anodisation (PA), sandblasting (MC04) and a combination of the last two (MC04 + PA). Their physicochemical properties were analysed by SEM/EDX, Raman, contact angle measurements and profilometry. In vitro responses were examined using human gingival fibroblastic (HGF) cells and THP-1 macrophages. Cytokine secretion, macrophage adhesion and gene expression were measured by ELISA, confocal microscopy and RT-PCR. Cell adhesion and collagen secretion were evaluated in HGF cultures. The adsorption of immune and regenerative proteins onto the surfaces was assessed employing nLC-MS/MS. MC04 + PA surfaces exhibited a change in the roughness, chemical composition and hydrophilicity of the material, showing more elongated HGF cells and a considerable increase in the area of cells exposed to the MC04 + PA surfaces. Moreover, cells cultured on MC04 + PA generally showed a reduction in the expression of proinflammatory genes (TNF-α, MCP-1, C5, NF-kB and ICAM-1) and an increase in the secretion of anti-inflammatory cytokines, such as IL-4. These results correlated with the proteomic data; we found preferential adsorption of proteins favouring cell adhesion, such as DSC1 and PCOC1. A considerable reduction in the adsorption of immunoglobulins and proteins associated with acute inflammatory response (including SAA4) was also observed. The study highlights the potential advantages of MC04 + PA surface treatment to modify dental implant abutments; it enhances their compatibility with soft tissues and reduces the inflammatory response.

Synthetic nanointerfacial bioengineering of Ti implants: on-demand regulation of implant-bone interactions for enhancing osseointegration.

Titanium and its alloys are the most commonly used biometals for developing orthopedic implants to treat various forms of bone fractures and defects, but their clinical performance is still challenged by the unfavorable mechanical and biological interactions at the implant-tissue interface, which substantially impede bone healing at the defects and reduce the quality of regenerated bones. Moreover, the impaired osteogenesis capacity of patients under certain pathological conditions such as diabetes and osteoporosis may further impair the osseointegration of Ti-based implants and increase the risk of treatment failure. To address these issues, various modification strategies have been developed to regulate the implant-bone interactions for improving bone growth and remodeling in situ. In this review, we provide a comprehensive analysis on the state-of-the-art synthetic nanointerfacial bioengineering strategies for designing Ti-based biofunctional orthopedic implants, with special emphasis on the contributions to (1) promotion of new bone formation and binding at the implant-bone interface, (2) bacterial elimination for preventing peri-implant infection and (3) overcoming osseointegration resistance induced by degenerative bone diseases. Furthermore, a perspective is included to discuss the challenges and potential opportunities for the interfacial engineering of Ti implants in a translational perspective. Overall, it is envisioned that the insights in this review may guide future research in the area of biometallic orthopedic implants for improving bone repair with enhanced efficacy and safety.

Osteoimmune-modulating and BMP-2-eluting anodised 3D printed titanium for accelerated bone regeneration.

3D printing of titanium (Ti) metal has potential to transform the field of personalised orthopaedics and dental implants. However, the impacts of controlled surface topographical features of 3D printed Ti implants on their interactions with the cellular microenvironment and incorporation of biological growth factors, which are critical in guiding the integration of implants with bone, are not well studied. In the present study, we explore the role of surface topological features of 3D printed Ti implants using an anodised titania nanotube (TiNT) surface layer in guiding their immune cell interaction and ability to deliver bioactive form of growth factors. TiNT layers with precisely controlled pore diameter (between 21and 130 nm) were anodically grown on 3D printed Ti surfaces to impart a nano-micro rough topology. Immune biomarker profiles at gene and protein levels show that anodised 3D Ti surfaces with smaller pores resulted in classical activation of macrophages (M1-like), while larger pores (i.e., >100 nm) promoted alternate activation of macrophages (M2-like). The in vitro bone mineralisation studies using the conditioned media from the immunomodulatory studies elucidate a clear impact of pore diameter on bone mineralisation. The tubular structure of TiNTs was utilised as a container to incorporate recombinant human bone morphogenetic protein-2 (BMP-2) in the presence of various sugar and polymeric cryoprotectants. Sucrose offered the most sustainable release of preserved BMP-2 from TiNTs. Downstream effects of released BMP-2 on macrophages as well as bone mineralisation were assessed showing bioactivity retention of the released rhBMP-2. Overall, the TiNT surface topography in combination with controlled, sustained, and local release of bioactive growth factors can potentially enhance the osseointegration outcomes of custom 3D printed Ti implants in the clinic.

Assessment of in-vivo corrosion of Ti and CoCrMo joint implants by electrochemical measurements in human synovial liquids

Understanding the corrosion behavior of biomedical materials in the human body is an essential step for the development of improved materials and clinical procedures in arthroplasty. In this work, the corrosion behavior of Ti and CoCrMo alloys in human synovial fluids directly extracted from patients was investigated through an electrochemical experimental protocol, including open circuit potential (OCP), electrochemical impedance spectroscopy (EIS) and potentiodynamic polarization measurements. The results show that the corrosion behavior of both materials largely depends on patients. The obtained corrosion rates of both materials correspond well to the metal ion release rate detected in patients with joint implants revealing the adequateness of the electrochemical experimental protocol for quantifying in-vivo corrosion of biomedical implants. Based on the results, no significant risk of galvanic corrosion of Ti/CoCrMo coupling is anticipated. The rates of wear-accelerated corrosion (one of the main degradation mechanisms of metallic artificial hip joints) were theoretically extracted from the present electrochemical measurements using an established tribocorrosion model. Those material loss rates are patient-dependent and can be up to two orders of magnitude higher than the static corrosion rates, indicating that the nature of the patient can critically affect the degradation rate of the joint implant.

Fibrous topology promoted pBMP2-activated matrix on titanium implants boost osseointegration.

Titanium (Ti) implants have been extensively used after surgical operations. Its surface bioactivity is of importance to facilitate integration with surrounding bone tissue, and ultimately ensure stability and long-term functionality of the implant. The plasmid DNA-activated matrix (DAM) coating on the surface could benefit osseointegration but is still trapped by poor transfection for further application, especially on the bone marrow mesenchymal stem cells (BMSCs) in vivo practical conditions. Herein, we constructed a DAM on the surface of fibrous-grained titanium (FG Ti) composed of phase-transition lysozyme (P) as adhesive, cationic arginine-rich lipid (RLS) as the transfection agent and plasmid DNA (pDNA) for bone morphology protein 2 (BMP2) expression. The cationic lipid RLS improved up to 30-fold higher transfection than that of commercial reagents (Lipofectamine 2000 and polyethyleneimine) on MSC. And importantly, Ti surface topology not only promotes the DAM to achieve high transfection efficiency (∼75.7% positive cells) on MSC due to the favorable combination but also reserves its contact induction effect for osteoblasts. Upon further exploration, the fibrous topology on FG Ti could boost pDNA uptake for gene transfection, and cell migration in MSC through cytoskeleton remodeling and induce contact guidance for enhanced osteointegration. At the same time, the cationic RLS together with adhesive P were both antibacterial, showing up to 90% inhibition rate against Escherichia coli and Staphylococcus aureus with reduced adherent microorganisms and disrupted bacteria. Finally, the FG Ti-P/pBMP2 implant achieved accelerated bone healing capacities through highly efficient gene delivery, aligned surface topological structure and increased antimicrobial properties in a rat femoral condylar defect model.