Orthopedic Biomaterials Research Articles

Biofilm morphology and antibiotic susceptibility of methicillin-resistant Staphylococcus aureus (MRSA) on poly-D,L-lactide-co-poly(ethylene glycol) (PDLLA-PEG) coated titanium

Biodegradable polymeric coatings are being explored as a preventive strategy for orthopaedic device-related infection. In this study, titanium surfaces (Ti) were coated with poly-D,L-lactide (PDLLA, (P)), polyethylene-glycol poly-D,L-lactide (PEGylated-PDLLA, (PP20)), or multi-layered PEGylated-PDLLA (M), with or without 1 % silver sulfadiazine. The aim was to evaluate their cytocompatibility, resistance to Staphylococcus aureus biofilm formation, and their potential to enhance the susceptibility of any biofilm formed to antibiotics. Using automated high-content screening confocal microscopy, biofilm formation of a clinical methicillin-resistant Staphylococcus aureus (MRSA) isolate expressing GFP was quantified, along with isogenic mutants that were unable to form polysaccharidic or proteinaceous biofilm matrices. The results showed that PEGylated-PDLLA coatings exhibited significant antibiofilm properties, with M showing the highest effect. This inhibitory effect was stronger in S. aureus biofilms with a matrix composed of proteins compared to those with an exopolysaccharide (PIA) biofilm matrix. Our data suggest that the antibiofilm effect may have been due to (i) inhibition of the initial attachment through microbial surface components recognising adhesive matrix molecules (MSCRAMMs), since PEG reduces protein surface adsorption via surface hydration layer and steric repulsion; and (ii) mechanical disaggregation and dispersal of microcolonies due to the bioresorbable/degradable nature of the polymers, which undergo hydration and hydrolysis over time. The disruption of biofilm morphology by the PDLLA-PEG co-polymers increased S. aureus susceptibility to antibiotics like rifampicin and fusidic acid. Adding 1 % AgSD provided additional early bactericidal effects on both biofilm and planktonic S. aureus. Additionally, the coatings were cytocompatible with immune cells, indicating their potential to enhance bacterial clearance and reduce bacterial colonisation of titanium-based orthopaedic biomaterials.

Chronic kidney disease: a contraindication for using biodegradable magnesium or its alloys as potential orthopedic implants?

Magnesium (Mg) has gained widespread recognition as a potential revolutionary orthopedic biomaterial. However, whether the biodegradation of the Mg-based orthopedic implants would pose a risk to patients with chronic kidney disease (CKD) remains undetermined as the kidney is a key organ regulating mineral homeostasis. A rat CKD model was established by a 5/6 subtotal nephrectomy approach, followed by intramedullary implantation of three types of pins: stainless steel, high pure Mg with high corrosion resistance, and the Mg–Sr–Zn alloy with a fast degradation rate. The long-term biosafety of the biodegradable Mg or its alloys as orthopedic implants were systematically evaluated. During an experimental period of 12 weeks, the implantation did not result in a substantial rise of Mg ion concentration in serum or major organs such as hearts, livers, spleens, lungs, or kidneys. No pathological changes were observed in organs using various histological techniques. No significantly increased iNOS-positive cells or apoptotic cells in these organs were identified. The biodegradable Mg or its alloys as orthopedic implants did not pose an extra health risk to CKD rats at long-term follow-up, suggesting that these biodegradable orthopedic devices might be suitable for most target populations, including patients with CKD.

In vitro co-culture models for the assessment of orthopedic antibacterial biomaterials.

The antibacterial biofunctionality of bone implants is essential for the prevention and treatment of implant-associated infections (IAI). In vitro co-culture models are utilized to assess this and study bacteria-host cell interactions at the implant interface, aiding our understanding of biomaterial and the immune response against IAI without impeding the peri-implant bone tissue regeneration. This paper reviews existing co-culture models together with their characteristics, results, and clinical relevance. A total of 36 studies were found involving in vitro co-culture models between bacteria and osteogenic or immune cells at the interface with orthopedic antibacterial biomaterials. Most studies (∼67%) involved co-culture models of osteogenic cells and bacteria (osteo-bac), while 33% were co-culture models of immune cells and bacterial cells (im-bac). All models involve direct co-culture of two different cell types. The cell seeding sequence (simultaneous, bacteria-first, and cell-first) was used to mimic clinically relevant conditions and showed the greatest effect on the outcome for both types of co-culture models. The im-bac models are considered more relevant for early peri-implant infections, whereas the osteo-bac models suit late infections. The limitations of the current models and future directions to develop more relevant co-culture models to address specific research questions are also discussed.

Effect of hydroxyapatite concentration and electrophoretic deposition (EPD) parameter process on hydroxyapatite/chitosan coating quality for porous titanium as orthopedic implant

ABSTRACT For orthopedic biomaterials, titanium and its alloys have shown great potential. Despite its benefits, the development of titanium for orthopedic implants is continuously growing. In order to reduce the problem of elastic mismatch, porous titanium has been developed, and to address the bioinert surface of titanium, surface modification has also been adapted to increase the bioactivity of titanium. In this research, electrophoretic deposition for depositing hydroxyapatite/chitosan (HA/Cs) on the porous titanium is being studied. For the electrophoretic deposition process, hydroxyapatite content in the solution was varied from 0.2, 0.4, and 0.6 wt.%, voltage deposition varied by 11 and 13 V, and deposition time was varied into 4 min and 8 min. Deposition weight, adhesion strength, and coating morphology were observed to compare the coating quality from each variable used in this experiment. Coating deposited from 0.2HA/Cs, 11 and 13 V for 8 min shows the best quality as shown to be homogeneous and good adhesion with the substrate.

Engineered three-dimensional bioactive scaffold for enhanced bone regeneration through modulating transplanted adipose derived mesenchymal stem cell and stimulating angiogenesis.

Titanium alloy materials are commonly used in orthopedic clinical treatments. However, conventional titanium implants usually lead to insufficient bone regeneration and integration because of mismatched biomechanics and poor bioactivities. To tackle these challenges, a porous titanium alloy scaffold with suitable mechanical properties was prepared using three-dimensional (3D) printing, and then an adipose-derived mesenchymal stem cell (ADSC) loaded platelet-rich plasma (PRP) gel was placed into the pores of the porous scaffold to construct a bioactive scaffold with dual functions of enhancing angiogenesis and osteogenesis. This bioactive scaffold showed good biocompatibility and supported cell viability proliferation and morphology of encapsulated ADSCs. Osteogenic and angiogenic growth factors in the PRP gel promoted the migration and angiogenesis of human umbilical vein endothelial cells (HUVECs) in vitro and enhanced osteogenic-related gene and protein expression in ADSCs, thus promoting osteogenic differentiation. After implantation into the femoral defects of rabbits, the bioactive scaffold promoted vascular network formation and the expression of osteogenesis-related proteins, thus effectively accelerating bone regeneration. Therefore, the osteogenic and angiogenic bioactive scaffold comprising a 3D printed porous titanium alloy scaffold, PRP, and ADSCs provides a promising design for orthopedic biomaterials with clinical transformation prospects and an effective strategy for bone defect treatment.

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.

Porous PLGA/MBG scaffold enhanced bone regeneration through osteoimmunomodulation

The role of osteoimmunomodulation in orthopedic biomaterials has been demonstrated to be crucial in the regulation of bone repair and regeneration. Macrophages, the primary effector cells in the immune response to biomaterials, are highly heterogeneous and plastic, making them a prime target for immunomodulation. Mesoporous bioactive glass (MBG) is widely recognized for its biocompatibility, osteoconductivity, osteoinductivity, and immunomodulatory properties. However, the impact of MBG content on macrophage response remains unclear. To fill this knowledge gap, we designed a series of hierarchical PLGA-based composite scaffolds with varying MBG contents (0%, 10%, 20% and 40%, named as P, P10M, P20M and P40M, respectively) to investigate the osteoimmunomodulatory effects of these scaffolds. Our findings indicated that the P10M scaffolds showed a faster immune response in the early stage and exhibited superior ability to shift the pro-inflammatory immune microenvironment towards an anti-inflammatory state in the later stage, thereby enhancing the angiogenic potential of HUVECs and the osteogenic capacity of BMSCs. Furthermore, the in vivo implantation demonstrated that the immune microenvironment induced by P10M scaffolds facilitated optimal neovascularization and ectopic bone formation. These findings establish a theoretical foundation for the development of bone immunoregulatory biomaterials doped with MBG, which can effectively promote bone repair and regeneration.

Research progress on biodegradable magnesium phosphate ceramics in orthopaedic applications.

To overcome critical size bone defects, calcium phosphate (CaP)-based ceramics have been widely explored. The compositional similarity with bone matrix and degradability are the main reasons for their selection in orthopaedic biomaterials. However, the low solubility rate under in vivo conditions raises concerns about these CaP groups, particularly hydroxyapatite (HA) and tricalcium phosphate (TCP) ceramics. Therefore, reliable and suitable degradable ceramics for bone defect repair are always an important research direction for researchers. The magnesium phosphate (MgP) group of bioceramics has been studied for orthopaedic applications and is comparatively new compared to traditional CaP ceramics. The role of magnesium in different biochemical processes, such as DNA stabilization, bone density maintenance, regulating Ca and Na ion channels, and cell proliferation and differentiation enhancement, is a key parameter for the development of MgP bioceramics. This article aims to give a comprehensive review of MgP ceramics in bone tissue engineering. Here, we have highlighted several preparation techniques, the existence of porosity, and the impact of metal ion doping on MgP bioceramics. Finally, in vitro and in vivo responses of MgP bioceramics in bone formation are discussed.

Biodegradable biomaterials in orthopedic surgery: A narrative review of the current evidence.

Biomaterials are routinely used in orthopedic surgery to fill bone defects, improve bone healing, and as degradable fixation material. A wide range of materials are currently in use, and the materials are chosen according to their bioactive properties. Osteoinductive materials stimulate bone healing by promoting osteogenesis. Osteoconductive materials facilitate bone growth on the surface of the material. Despite the many materials in use and an increasing number of published studies, randomized controlled trials on the subject are scarce. This review aims to summarize the history of biodegradable biomaterials and also the published level I evidence currently available on orthopedic biomaterials. Most of the studies have been superiority trials with non-significant differences compared to conventional treatment options, confirming that several biomaterials are suitable treatment options for multiple indications including bone and/or tendon fixation, filling bone defects, and spinal fusion. Biomaterials help to avoid donor site complications associated with autogenous bone grafts and often eliminate the need for implant removal. However, the surgical technique may in some cases be more demanding than with conventional methods. Careful consideration of the pros and cons is therefore recommended in clinical practice. Biodegradable biomaterials complement the range of available treatment options in several fields of orthopedic surgery. However, some biomaterials performed worse than expected and were not recommended for clinical use, emphasizing the need for high-quality randomized trials. It is also noteworthy that several trials included only a limited number of patients, rendering the interpretation of the results of these underpowered studies challenging.

Elucidating osseointegration in vivo in 3D printed scaffolds eliciting different foreign body responses.

Osseointegration between biomaterial and bone is critical for the clinical success of many orthopaedic and dental implants. However, the mechanisms of in vivo interfacial bonding formation and the role of immune cells in this process remain unclear. In this study, we investigated the bone-scaffold material interfaces in two different 3D printed porous scaffolds (polymer/hydroxyapatite and sintered hydroxyapatite) that elicited different levels of foreign body response (FBR). The polymer/hydroxyapatite composite scaffolds elicited more intensive FBR, which was evidenced by more FBR components, such as macrophages/foreign body giant cells and fibrous tissue, surrounding the material surface. Sintered hydroxyapatite scaffolds showed less intensive FBR compared to the composite scaffolds. The interfacial bonding appeared to form via new bone first forming within the pores of the scaffolds followed by growing towards strut surfaces. In contrast, it was previously thought that bone regeneration starts at biomaterial surfaces via osteogenic stem/progenitor cells first attaching to them. The material-bone interface of the less immunogenic hydroxyapatite scaffolds was heterogenous across all samples, evidenced by the coexistence of osseointegration and FBR components. The presence of FBR components appeared to inhibit osseointegration. Where FBR components were present there was no osseointegration. Our results offer new insight on the in vivo formation of bone-material interface, which highlights the importance of minimizing FBR to facilitate osseointegration for the development of better orthopaedic and dental biomaterials.

Discussion and Concern on Animal Study for Orthopaedic Implantable Devices

In recent years, new orthopaedic implantable devices continue to emerge, which require higher requirements for technical evaluation. Animal study is an important part of the research and development process for the new orthopedic implantable devices, which provides relevant evidence for product design and stereotyping. By introducing the purpose of animal study, and the application of 3R principle (replacement, reduction, refinement) in this field, we summarize the concern on the animal study, in order to provide reference for the development and research of new orthopedic implantable devices and biomaterials. At the same time, the application of evidence-based research methods such as systematic review in the field is introduced, which provides new tools and approaches for the technical review and regulatory science.

Enhanced in vitro immersion behavior and antibacterial activity of NiTi orthopedic biomaterial by HAp-Nb2O5 composite deposits

NiTi is a class of metallic biomaterials, benefit from superelastic behavior, high biocompatibility, and favorable mechanical properties close to that of bone. However, the Ni ion leaching, poor bioactivity, and antibacterial activity limit its clinical applications. In this study, HAp-Nb2O5 composite layers were PC electrodeposited from aqueous electrolytes containing different concentrations of the Nb2O5 particles, i.e., 0–1 g/L, to evaluate the influence of the applied surface engineering strategy on in vitro immersion behavior, Ni2+ ion leaching level, and antibacterial activity of the bare NiTi. Surface characteristics of the electrodeposited layers were analyzed using SEM, TEM, XPS, and AFM. The immersion behavior of the samples was comprehensively investigated through SBF and long-term PBS soaking. Gram-negative Escherichia coli (E. coli) and Gram-positive Staphylococcus aureus (S. aureus) infective reference bacteria were employed to address the antibacterial activity of the samples. The results illustrated that the included particles led to more compact and smoother layers. Unlike bare NiTi, composite layers stimulated apatite formation upon immersion in both SBF and PBS media. The concentration of the released Ni2+ ion from the composite layer, containing 0.50 g/L Nb2O5 was ≈ 60% less than that of bare NiTi within 30 days of immersion in the corrosive PBS solution. The Nb2O5-reinforced layers exhibited high anti-adhesive activity against both types of pathogenic bacteria. The hybrid metallic-ceramic system comprising HAp-Nb2O5-coated NiTi offers the prospect of a potential solution for clinical challenges facing the orthopedic application of NiTi.

Enhancing biocompatibility, mechanical properties, and corrosion resistance of laser cladding β-TiNb coatings

β-type TiNb biomedical alloys have received quite significant attention rooted in their excellent comprehensive performance. Nevertheless, their practical application is hampered by relatively poor performance and biological toxicity. Herein, TixNb alloy coatings were fabricated on the surface of Ti6Al4V (TC4) by laser cladding to evade the property-toxicity trade-off. Biocompatibility and mechanical properties, as well as the corrosion resistance of the TixNb alloy coatings, were discussed. The results show that the microstructure is composed of β grains and a small amount of the α″ martensite phase uniformly precipitated around them. The rapid melting process of laser cladding promotes the formation of the β phase, which improves the microhardness and wear resistance of the coating. However, the corrosion resistance was significantly improved due to the formation of the densification and stabilization of the passive films formed on the coating’s surface. Benefiting from the superior wettability and the biologically active sites of Ti and Nb on the alloy surface, MG-63 cells adhered to the coating’s surfaces in spindle shape and proliferated rapidly in cell experiments, denoting that the coatings have better biocompatibility than TC4. Hereby, the obtained TixNb laser cladding coatings with excellent mechanical properties and biocompatibility have extensive application prospects in the field of orthopedic biomaterials.

Friend or foe? Inflammation and the foreign body response to orthopedic biomaterials.

The use of biomaterials and implants for joint replacement, fracture fixation, spinal stabilization and other orthopedic indications has revolutionized patient care by reliably decreasing pain and improving function. These surgical procedures always invoke an acute inflammatory reaction initially, that in most cases, readily subsides. Occasionally, chronic inflammation around the implant develops and persists; this results in unremitting pain and compromises function. The etiology of chronic inflammation may be specific, such as with infection, or be unknown. The histological hallmarks of chronic inflammation include activated macrophages, fibroblasts, T cell subsets, and other cells of the innate immune system. The presence of cells of the adaptive immune system usually indicates allergic reactions to metallic haptens. A foreign body reaction is composed of activated macrophages, giant cells, fibroblasts, and other cells often distributed in a characteristic histological arrangement; this reaction is usually due to particulate debris and other byproducts from the biomaterials used in the implant. Both chronic inflammation and the foreign body response have adverse biological effects on the integration of the implant with the surrounding tissues. Strategies to mitigate chronic inflammation and the foreign body response will enhance the initial incorporation and longevity of the implant, and thereby, improve long-term pain relief and overall function for the patient. The seminal research performed in the laboratory of Dr. James Anderson and co-workers has provided an inspirational and driving force for our laboratory's work on the interactions and crosstalk among cells of the mesenchymal, immune, and vascular lineages, and orthopedic biomaterials. Dr. Anderson's delineation of the fundamental biologic processes and mechanisms underlying acute and chronic inflammation, the foreign body response, resolution, and eventual functional integration of implants in different organ systems has provided researchers with a strategic approach to the use of biomaterials to improve health in numerous clinical scenarios.

Regulation of Osteoimmune Microenvironment and Osteogenesis by 3D-Printed PLAG/black Phosphorus Scaffolds for Bone Regeneration.

The treatment of bone defects remains a significant challenge to be solved clinically. Immunomodulatory properties of orthopedic biomaterials have significance in regulating osteoimmune microenvironment for osteogenesis. A lactic acid-co-glycolic acid (PLGA) scaffold incorporates black phosphorus (BP) fabricated by 3D printing technology to investigate the effect of BP on osteoimmunomodulation and osteogenesis in site. The PLGA/BP scaffold exhibits suitable biocompatibility, biodegradability, and mechanical properties as an excellent microenvironment to support new bone formation. The studies' result also demonstrate that the PLGA/BP scaffolds are able to recruit and stimulate macrophages M2polarization, inhibit inflammation, and promote human bone marrow mesenchymal stem cells (hBMSCs) proliferation and differentiation, which in turn promotes bone regeneration in the distal femoral defect region of steroid-associated osteonecrosis (SAON) rat model. Moreover, it is screened and demonstrated that PLGA/BP scaffolds can promote osteogenic differentiation by transcriptomic analysis, and PLGA/BP scaffolds promote osteogenic differentiation and mineralization by activating PI3K-AKTsignaling pathway in hBMSC cells. In this study, it is shown that the innovative PLGA/BP scaffolds are extremely effective in stimulating bone regeneration by regulating macrophage M2 polarization and a new strategy for the development of biomaterials that can be used to repair bone defects is offered.

Translation of nanotechnology-based implants for orthopedic applications: current barriers and future perspective.

The objective of bioimplant engineering is to develop biologically compatible materials for restoring, preserving, or altering damaged tissues and/or organ functions. The variety of substances used for orthopedic implant applications has been substantially influenced by modern material technology. Therefore, nanomaterials can mimic the surface properties of normal tissues, including surface chemistry, topography, energy, and wettability. Moreover, the new characteristics of nanomaterials promote their application in sustaining the progression of many tissues. The current review establishes a basis for nanotechnology-driven biomaterials by demonstrating the fundamental design problems that influence the success or failure of an orthopedic graft, cell adhesion, proliferation, antimicrobial/antibacterial activity, and differentiation. In this context, extensive research has been conducted on the nano-functionalization of biomaterial surfaces to enhance cell adhesion, differentiation, propagation, and implant population with potent antimicrobial activity. The possible nanomaterials applications (in terms of a functional nanocoating or a nanostructured surface) may resolve a variety of issues (such as bacterial adhesion and corrosion) associated with conventional metallic or non-metallic grafts, primarily for optimizing implant procedures. Future developments in orthopedic biomaterials, such as smart biomaterials, porous structures, and 3D implants, show promise for achieving the necessary characteristics and shape of a stimuli-responsive implant. Ultimately, the major barriers to the commercialization of nanotechnology-derived biomaterials are addressed to help overcome the limitations of current orthopedic biomaterials in terms of critical fundamental factors including cost of therapy, quality, pain relief, and implant life. Despite the recent success of nanotechnology, there are significant hurdles that must be overcome before nanomedicine may be applied to orthopedics. The objective of this review was to provide a thorough examination of recent advancements, their commercialization prospects, as well as the challenges and potential perspectives associated with them. This review aims to assist healthcare providers and researchers in extracting relevant data to develop translational research within the field. In addition, it will assist the readers in comprehending the scope and gaps of nanomedicine's applicability in the orthopedics field.

Evading stability-biocompatibility tradeoff in TiNb coatings with armour-like super hydrophilic micro-nano structure surface

Modification of micro-nano structures on the surface of medical implants using a femtosecond laser (FSL) can improve cell behavior, increase tissue and material bonding strength, and promote preferred osseointegration. Nevertheless, the FSL processed micro-nano structures suffer from a compromise between biocompatibility and structural stability. Herein, a Ti32·5Nb alloy laser cladding (LC) coating was initially created on the surface of the Ti6Al4V (TC4) substrate, followed by the construction of an armour-like micro-nano structure with structural stability and biocompatibility on the coating surface. The results show that the microhardness, were resistance and corrosion resistance of the coatings were significantly improved. It efficiently prevents wear damage to the micro-nano structure by modifying the surface armour structure of FSL. In addition, a considerable quantity of hydroxyapatite (HA) is deposited on the surface, resulting in a Ca/P ratio that is closer to that of osteogenesis. Moreover, the surface structure is a periodic micro-nano structure with three-level distribution, which can guide the migration and proliferation of cell nanofiber matrix. Human osteosarcoma cells (MG-63) adhere to the surface and proliferate rapidly along the direction of the micro-nano structure. Hereby, the armoured micro-nano structures developed exhibit sustained wear resistance and great biocompatibility. It offers a wide range of applications in the field of surface modification of orthopedic biomaterials.

Recent developments in nanomaterials for upgrading treatment of orthopedics diseases.

Nanotechnology has changed science in the last three decades. Recent applications of nanotechnology in the disciplines of medicine and biology have enhanced medical diagnostics, manufacturing, and drug delivery. The latest studies have demonstrated this modern technology's potential for developing novel methods of disease detection and treatment, particularly in orthopedics. According to recent developments in bone tissue engineering, implantable substances, diagnostics and treatment, and surface adhesives, nanomedicine has revolutionized orthopedics. Numerous nanomaterials with distinctive chemical, physical, and biological properties have been engineered to generate innovative medication delivery methods for the local, sustained, and targeted delivery of drugs with enhanced therapeutic efficacy and minimal or no toxicity, indicating a very promising strategy for effectively controlling illnesses. Extensive study has been carried out on the applications of nanotechnology, particularly in orthopedics. Nanotechnology can revolutionize orthopedics cure, diagnosis, and research. Drug delivery precision employing nanotechnology using gold and liposome nanoparticles has shown especially encouraging results. Moreover, the delivery of drugs and biologics for osteosarcoma is actively investigated. Different kind of biosensors and nanoparticles has been used in the diagnosis of bone disorders, for example, renal osteodystrophy, Paget's disease, and osteoporosis. The major hurdles to the commercialization of nanotechnology-based composite are eventually examined, thus helping in eliminating the limits in connection to some pre-existing biomaterials for orthopedics, important variables like implant life, quality, cure cost, and pain and relief from pain. The potential for nanotechnology in orthopedics is tremendous, and most of it looks to remain unexplored, but not without challenges. This review aims to highlight the up tp date developments in nanotechnology for boosting the treatment modalities for orthopedic ailments. Moreover, we also highlighted unmet requirements and present barriers to the practical adoption of biomimetic nanotechnology-based orthopedic treatments.

Application of piezoelectric materials in the field of bone: a bibliometric analysis.

In the past 4decades, many articles have reported on the effects of the piezoelectric effect on bone formation and the research progress of piezoelectric biomaterials in orthopedics. The purpose of this study is to comprehensively evaluate all existing research and latest developments in the field of bone piezoelectricity, and to explore potential research directions in this area. To assess the overall trend in this field over the past 40 years, this study comprehensively collected literature reviews in this field using a literature retrieval program, applied bibliometric methods and visual analysis using CiteSpace and R language, and identified and investigated publications based on publication year (1984-2022), type of literature, language, country, institution, author, journal, keywords, and citation counts. The results show that the most productive countries in this field are China, the United States, and Italy. The journal with the most publications in the field of bone piezoelectricity is the International Journal of Oral & Maxillofacial Implants, followed by Implant Dentistry. The most productive authors are Lanceros-Méndez S, followed by Sohn D.S. Further research on the results obtained leads to the conclusion that the research direction of this field mainly includes piezoelectric surgery, piezoelectric bone tissue engineering scaffold, manufacturing artificial cochleae for hearing loss patients, among which the piezoelectric bone tissue engineering scaffold is the main research direction in this field. The piezoelectric materials involved in this direction mainly include polyhydroxybutyrate valerate, PVDF, and BaTiO3.

Progress of research on graphene and its derivatives in bone and cartilage repair.

In recent years, graphene and its derivatives have gained wide attention in the biomedical field due to their good physicochemical properties, biocompatibility, and bioactivity. Its good antibacterial, osteoinductive and drug-carrying properties make it a promising application in the field of orthopedic biomaterials. This paper introduces the research progress of graphene and its derivatives in bone tissue engineering and cartilage tissue engineering and presents an outlook on the future development of graphene-based materials in orthopedics.