Hierarchical antibiotic delivery system based on calcium phosphate cement/montmorillonite-gentamicin sulfate with drug release pathways.

Antibiotic-loaded calcium phosphate cement (CPC) has emerged as a promising biomaterial for drug delivery in orthopedics. However, there are problems such as the burst release of antibiotics, low cumulative release ratio, inappropriate release cycle, inferior mechanical strength, and poor anti-collapse properties. In this research, montmorillonite-gentamicin (MMT-GS) was fabricated by solution intercalation method and served as the drug release pathways in CPC to avoid burst release of GS, achieving promoted cumulative release ratios and a release cycle matched the time of inflammatory response. The results indicated that the highest cumulative release ratio and release concentration of GS in CPC/MMT-GS was 94.1 ± 2.8 % and 1183.05 µg/mL, and the release cycle was up to 504 h. In addition, the hierarchical GS delivery system was divided into three stages, and the kinetics followed the Korsmeyer-Peppas model, the zero-order model, and the diffusion-dissolution model, respectively. Meanwhile, the compressive strength of CPC/MMT-GS was up to 51.33 ± 3.62 MPa. Antibacterial results demonstrated that CPC/MMT-GS exhibited excellent in vitro long-lasting antibacterial properties to E. coli and S. aureus. Furthermore, CPC/MMT-GS promoted osteoblast proliferation and exhibited excellent in vivo histocompatibility. Therefore, CPC/MMT-GS has favorable application prospects in the treatment of bone defects with bacterial infections and inflammatory reactions.

High performance injectable Mg doped bioactive glass bone cement for the regulation of osteogenic immune microenvironment.

Although calcium phosphate has been extensively utilized in orthopedic applications such as spine, limbs, dentistry, and maxillofacial surgery, the lack of osteoinductive properties often hinders its effectiveness in treating bone defects resulting from pathological micro-environment such as tumor surgery, osteoporosis, osteomyelitis, and diabetic. Therefore, a novel bone cement based on magnesium-doped bioactive glass was developed in this study. The moderate release of magnesium ions improved the mechanical properties by controlling the crystal size of hydroxyapatite. Through detailed discussion of element content and heat treatment temperature, it was found that 2Mg-BG-800 was suitable for the construction of bone cement. 2Mg-BG-BC exhibited favorable initial (15 min) and final (30 min) setting time, compressive strength (29.45 MPa), compressive modulus (1851.49 MPa), injectability, and shape-adaptability. Furthermore, Mg-BG-BC demonstrated the ability to enhance the osteogenic differentiation of BMSCs, and induce macrophage polarization towards the M2 phenotype, suggesting its potential for osteoporotic fracture regeneration.

Surface functionalization of calcium magnesium phosphate cements with alginate sodium for enhanced bone regeneration via TRPM7/PI3K/Akt signaling pathway.

Although calcium­magnesium phosphate cements (CMPCs) have been widely applied to treating critical-size bone defects, their repair efficiency is unsatisfactory owing to their weak surface bioactivity and uncontrolled ion release. In this study, we lyophilized alginate sodium (AS) as a coating onto HAp/K-struvite (H@KSv) to develop AS/HAp/K-struvite (AH@KSv), which promotes bone regeneration. The compressive strength and hydrophilicity of AH@KSv significantly improved, leading to enhanced cell adhesion in vitro. Importantly, the SA coating enables continuous ions release of Mg2+ and Ca2+, finally leading to enhanced osteogenesis in vitro/vivo and different patterns of new bone ingrowth in vivo. Furthermore, these composites increased the expression levels of biomarkers of the TRPM7/PI3K/Akt signaling pathway via an equilibrium effect of Mg2+ to Ca2+. In conclusion, our study provides novel insights into the mechanisms of Mg-based biomaterials for bone regeneration.

Preclinical Evaluation of Bioactive Small Intestinal Submucosa-PMMA Bone Cement for Vertebral Augmentation.

In vertebroplasty and kyphoplasty, bioinert poly(methyl methacrylate) (PMMA) bone cement is a conventional filler employed for quick stabilization of osteoporotic vertebral compression fractures (OVCFs). However, because of the poor osteointegration, excessive stiffness, and high curing temperature of PMMA, the implant loosens, the adjacent vertebrae refracture, and thermal necrosis of the surrounding tissue occurs frequently. This investigation addressed these issues by incorporating the small intestinal submucosa (SIS) into PMMA (SIS-PMMA). In vitro analyses revealed that this new SIS-PMMA bone cement had improved porous structure, as well as reduced compressive modulus and polymerization temperature compared with the original PMMA. Furthermore, the handling properties of SIS-PMMA bone cement were not significantly different from PMMA. The in vitro effect of PMMA and SIS-PMMA was investigated on MC3T3-E1 cells via the Transwell insert model to mimic the clinical condition or directly by culturing cells on the bone cement samples. The results indicated that SIS addition substantially enhanced the proliferation and osteogenic differentiation of MC3T3-E1 cells. Additionally, the bone cement's biomechanical properties were also assessed in a decalcified goat vertebrae model with a compression fracture, which indicated the SIS-PMMA had markedly increased compressive strength than PMMA. Furthermore, it was proved that the novel bone cement had good biosafety and efficacy based on the International Standards and guidelines. After 12 weeks of implantation, SIS-PMMA indicated significantly more osteointegration and new bone formation ability than PMMA. In addition, vertebral bodies with cement were also extracted for the uniaxial compression test, and it was revealed that compared with the PMMA-implanted vertebrae, the SIS-PMMA-implanted vertebrae had greatly enhanced maximum strength. Overall, these findings indicate the potential of SIS to induce efficient fixation between the modified cement surface and the host bone, thereby providing evidence that the SIS-PMMA bone cement is a promising filler for clinical vertebral augmentation.

Investigating the in vitro antibacterial efficacy of composite bone cement incorporating natural product-based monomers and gentamicin.

OBJECTIVE: The objective of this study is to investigate the impact of four natural product extracts, namely, aloe-emodin, quercetin, curcumin, and tannic acid, on the in vitro bacteriostatic properties and biocompatibility of gentamicin-loaded bone cement and to establish an experimental groundwork supporting the clinical utility of antibiotic-loaded bone cements (ALBC). METHODS: Based on the components, the bone cement samples were categorized as follows: the gentamicin combined with aloe-emodin group, the gentamicin combined with quercetin group, the gentamicin combined with curcumin group, the gentamicin combined with tannic acid group, the gentamicin group, the aloe-emodin group, the quercetin group, the curcumin group, and the tannic acid group. Using the disk diffusion test, we investigated the antibacterial properties of the bone cement material against Staphylococcus aureus (n = 4). We tested cell toxicity and proliferation using the cell counting kit-8 (CCK-8) and examined the biocompatibility of bone cement materials. RESULTS: The combination of gentamicin with the four natural product extracts resulted in significantly larger diameters of inhibition zones compared to gentamicin alone, and the difference was statistically significant (P < 0.05). Except for the groups containing tannic acid, cells in all other groups showed good proliferation across varying time intervals without displaying significant cytotoxicity (P < 0.05). CONCLUSION: In this study, aloe-emodin, quercetin, curcumin, and tannic acid were capable of enhancing the in vitro antibacterial performance of gentamicin-loaded bone cement against S. aureus. While the groups containing tannic acid displayed moderate cytotoxicity in in vitro cell culture, all other groups showed no discernible cytotoxic effects.

Injectable macroporous naturally-derived apatite bone cement as a potential trabecular bone substitute.

In this study, we have formulated a novel apatite bone cements derived from natural sources (i.e. eggshell and fishbone) with improved qualities that is, porosity, resorbability, biological activity, and so forth. The naturally-derived apatite bone cement (i.e. FBDEAp) was prepared by mixing hydroxyapatite (synthesized from fishbone) and tricalcium phosphate (synthesized from eggshell) as a solid phase with a liquid phase (a dilute acidic blend of cement binding accelerator and biopolymers like gelatin and chitosan) with polysorbate (as liquid porogen) to get a desired bone cement paste. The prepared cement paste sets within the clinically acceptable setting time (≤20 min), easily injectable (>85%) through hands and exhibits physiological pH stability (7.3-7.4). The pure apatite phased bone cement was confirmed by x-ray diffraction and Fourier transform infrared spectroscopy analyses. The FBDEAp bone cement possesses acceptable compressive strength (i.e. 5-7 MPa) within trabecular bone range and is resorbable up to 28% in simulated body fluid solution within 12 weeks of incubation at physiological conditions. The FBDEAp is macroporous in nature (average pore size ~50-400 µm) with interconnected pores verified by SEM and micro-CT analyses. The FBDEAp showed significantly increased MG63 cell viability (>125% after 72 h), cell adhesion, proliferation, and key osteogenic genes expression levels (up to 5-13 folds) compared to the synthetically derived, synthetic and eggshell derived as well as synthetic and fishbone derived bone cements. Thus, we strongly believe that our prepared FBDEAp bone cement can be used as potential trabecular bone substitute in orthopedics.

Simultaneous Regulation of the Mechanical/Osteogenic Capacity of Brushite Calcium Phosphate Cement by Incorporating with Poly(ethylene glycol) Dicarboxylic Acid.

Brushite calcium phosphate cement (brushite CPC) is a prospective bone repair material due to its ideal resorption rates in vivo. However, the undesirable mechanical property and bioactivity limited its availability in clinic application. To address this issue, incorporating polymeric additives has emerged as a viable solution. In this study, poly(ethylene glycol) dicarboxylic acid, PEG(COOH), was synthesized and employed as the polymeric additive. The setting behavior, anti-washout ability, mechanical property, degradation rate, and osteogenic capacity of brushite CPC were regulated by incorporating PEG(COOH). The incorporation of PEG(COOH) with carboxylic acid groups demonstrated a positive effect on both mechanical properties and osteogenic activity in bone repair. This study offers valuable insights and suggests a promising strategy for the development of materials in bone tissue engineering.

Enhanced osteogenic and bactericidal performance of premixed calcium phosphate cement with photocrosslinked alginate thin film.

The increasing prevalence of implant-associated infections (IAI) in orthopedics remains a public health challenge. Calcium phosphates (CaPs) are critical biomaterials in dental treatments and bone regeneration. It is highly desirable to endow CaPs with antibacterial properties. To achieve this purpose, we developed a photocrosslinked methacrylated alginate co-calcium phosphate cement (PMA-co-PCPC) with antibacterial properties, using α-tricalcium phosphate (α-TCP) powders with 16% amorphous contents as solid phase, liquid phases containing CuCl2 and SrCl2 as an inhibitor, and CaCl2 as an activator to construct PCPC. When CaCl2 started to activate the hydration reaction, Sr2+ or Cu2+ ions were exchanged with Ca2+, and α-TCP dissolution was restarted and gradually hydrated to form calcium-deficient hydroxyapatite (CDHA). PMA was added to crosslink with Cu/Sr ions and form gel-layer-wrapped hydrated CDHA. This study explored the binding mechanism of PMA and PCPC and the ion release rule of Ca2+ → Sr2+/Cu2+, optimized the construction of several antibacterial PMA-co-PCPC materials, and analyzed the physical, chemical, and biological properties. Because of the combined effect of Cu and Sr ions, the scaffold exhibited a potential antibacterial activity, promoting bone formation and vascular regeneration. This work provides a basis for designing antibacterial calcium phosphate biomaterials with controllable treatment, which is an important characteristic for preventing IAI of biomaterials.

Regulation of the antibiotic elution profile from tricalcium phosphate bone cement by addition of bioactive glass.

This work aimed at tailoring of different properties of antibacterial drug delivery Ca-phosphate cements by incorporation of bioactive glass (BG). The cements were prepared from beta-tricalcium phosphate cement (ß-TCP) and BG based on 50 SiO2-20 CaO-15 Na2O-7 B2O3-4 P2O5-4 Al2O3 wt% with different percentages of BG [5, 10, 15, and 20% (w/w)]. The composite cements were characterized by XRD, FTIR, and TEM. Moreover, in vitro bioactivity and biodegradation were evaluated in the simulated body fluid (SBF) at 37 °C. In addition, physical properties and mechanical strength were determined. Also, the effect of glass addition on the drug release profile was examined using gentamicin. Finally, the antimicrobial activity was studied against Staphylococcus aureus, Pseudomonas aeruginosa, and Klebsiella pneumonia bacteria, one unicellular fungal strain (Candida albicans), and one multicellular fungal strain (Mucor racemosus). The results showed that after soaking in SBF, the compression strength values ranged from 14 to 36 MPa, the bulk densities and porosities were within 1.35 to 1.49 g/cm3 and 51.3 to 44.71%, respectively. Furthermore, gentamicin was released in a sustained manner, and BG decreased the released drug amount from ~ 80% (in pure ß-TCP) to 47-53% in the composite cements. A drug release profile that is sustained by all samples was achieved. The antimicrobial test showed good activity of gentamicin-conjugated cements against bacteria and fungi used in this study. Additionally, cytotoxicity results proved that all samples were safe on MG-63 cells up to 50 µg/mL with no more than 7-12% dead cells. From the view of the physico-mechanical properties, bioactivity, biodegradation, and drug release rate, 20BG/ß-TCP sample was nominated for practical bone grafting material, where it showed appropriate setting time and a relatively high mechanical strength suitable for cancellous bone.

Preferentially Biodegradable Gypsum Fibers Endowing Invisible Microporous Structures and Enhancing Osteogenic Capability of Calcium Phosphate Cements.

It is known that hydroxyapatite-type calcium phosphate cement (CPC) shows appreciable self-curing properties, but the phase transformation products often lead to slow biodegradation and disappointing osteogenic responses. Herein, we developed an innovative strategy to endow invisible micropore networks, which could tune the microstructures and biodegradation of α-tricalcium phosphate (α-TCP)-based CPC by gypsum fibers, and the osteogenic capability of the composite cements could be enhanced in vivo. The gypsum fibers were prepared via extruding the gypsum powder/carboxylated chitosan (CC) slurry through a 22G nozzle (410 µm in diameter) and collecting with a calcium salt solution. Then, the CPCs were prepared by mixing the α-TCP powder with gypsum fibers (0-24 wt %) and an aqueous solution to form self-curing cements. The physicochemical characterizations showed that injectability was decreased with an increase in the fiber contents. The µCT reconstruction demonstrated that the gypsum fiber could be distributed in the CPC substrate and produce long-range micropore architectures. In particular, incorporation of gypsum fibers would tune the ion release, produce tunnel-like pore networks in vitro, and promote new bone tissue regeneration in rabbit femoral bone defects in vivo. Appropriate gypsum fibers (16 and 24 wt %) could enhance bone defect repair and cement biodegradation. These results demonstrate that the highly biodegradable cement fibers could mediate the microstructures of conventional CPC biomaterials, and such a bicomponent composite strategy may be beneficial for expanding clinical CPC-based applications.

Finite element analysis of vertebroplasty in the osteoporotic T11-L1 vertebral body: Effects of bone cement formulation.

Vertebral compression fractures are one of the most severe clinical consequences of osteoporosis and the most common fragility fracture afflicting 570 and 1070 out of 100,000 men and women worldwide, respectively. Vertebroplasty (VP), a minimally invasive surgical procedure that involves the percutaneous injection of bone cement, is one of the most efficacious methods to stabilise osteoporotic vertebral compression fractures. However, postoperative fracture has been observed in up to 30% of patients following VP. Therefore, this study aims to investigate the effect of different injectable bone cement formulations on the stress distribution within the vertebrae and intervertebral discs due to VP and consequently recommend the optimal cement formulation. To achieve this, a 3D finite element (FE) model of the T11-L1 vertebral body was developed from computed tomography scan data of the spine. Osteoporotic bone was modeled by reducing the Young's modulus by 20% in the cortical bone and 74% in cancellous bone. The FE model was subjected to different physiological movements, such as extension, flexion, bending, and compression. The osteoporotic model caused a reduction in the average von Mises stress compared with the normal model in the T12 cancellous bone and an increment in the average von Mises stress value at the T12 cortical bone. The effects of VP using different formulations of a novel injectable bone cement were modeled by replacing a region of T12 cancellous bone with the materials. Due to the injection of the bone cement at the T12 vertebra, the average von Mises stresses on cancellous bone increased and slightly decreased on the cortical bone under all loading conditions. The novel class of bone cements investigated herein demonstrated an effective restoration of stress distribution to physiological levels within treated vertebrae, which could offer a potential superior alternative for VP surgery as their anti-osteoclastogenic properties could further enhance the appeal of their fracture treatment and may contribute to improved patient recovery and long-term well-being.

Incorporation of black phosphorus nanosheets into poly(propylene fumarate) biodegradable bone cement to enhance bioactivity and osteogenesis.

BACKGROUND: Injectable bone cement is commonly used in clinical orthopaedics to fill bone defects, treat vertebral compression fractures, and fix joint prostheses during joint replacement surgery. Poly(propylene fumarate) (PPF) has been proposed as a biodegradable and injectable alternative to polymethylmethacrylate (PMMA) bone cement. Recently, there has been considerable interest in two-dimensional (2D) black phosphorus nanomaterials (BPNSs) in the biomedical field due to their excellent photothermal and osteogenic properties. In this study, we investigated the biological and physicochemical qualities of BPNSs mixed with PPF bone cement created through thermal cross-linking. METHODS: PPF was prepared through a two-step process, and BPNSs were prepared via a liquid phase stripping method. BP/PPF was subsequently prepared through thermal cross-linking, and its characteristics were thoroughly analysed. The mechanical properties, cytocompatibility, osteogenic performance, degradation performance, photothermal performance, and in vivo toxicity of BP/PPF were evaluated. RESULTS: BP/PPF exhibited low cytotoxicity levels and mechanical properties similar to that of bone, whereas the inclusion of BPNSs promoted preosteoblast adherence, proliferation, and differentiation on the surface of the bone cement. Furthermore, 200 BP/PPF demonstrated superior cytocompatibility and osteogenic effects, leading to the degradation of PPF bone cement and enabling it to possess photothermal properties. When exposed to an 808-nm laser, the temperature of the bone cement increased to 45-55 °C. Furthermore, haematoxylin and eosin-stained sections from the in vivo toxicity test did not display any anomalous tissue changes. CONCLUSION: BP/PPF exhibited mechanical properties similar to that of bone: outstanding photothermal properties, cytocompatibility, and osteoinductivity. BP/PPF serves as an effective degradable bone cement and holds great potential in the field of bone regeneration.

Preparation and characterizations of antibacterial poly(methyl methacrylate) bone cement via copolymerization with a quaternary ammonium monomer of dimethylaminotriclosan methacrylate.

Poly (methyl methacrylate) (PMMA) bone cement relies on the loaded antibiotic to realize the antibacterial purpose. But the exothermic behavior during setting often makes temperature-sensitive antibiotics inactivated. It is necessary to develop new material candidates to replace antibiotics. In this study, a new quaternary ammonium methacrylate (QAM) monomer called dimethylaminetriclosan methacrylate (DMATCM) was designed by the quaternization between 2-(Dimethylamino)ethyl methacrylate and triclosan, then employed as the modifier to explore the feasibility of equipping bone cement with antibacterial activity, and to investigate the variations on the physical and biological performances brought by the substitution ratio of DMATCM to MMA. Results showed that DMATCM opened its C=C bonding to participate in the MMA polymerization, and the quaternary ammonium group helped it to perform broad-spectrum antibacterial property against both Gram-positive Staphylococcus aureus and Gram-negative Escherichia coli. With an increased substitution ratio of DMATCM to MMA, the glass transition temperatures, the maximum exothermic temperatures, and the contact angles of bone cements declined, but the residual monomer contents, the fluid uptakes, and the setting times under Vical indentation increased. Long-term soaking made almost no changes to the weight loss and the mechanical properties of DMATCM-modified cements with lower substitution ratios of 0∼20%, and the activation rather enhanced the strengths of uncured AMBC-4 and AMBC-5 samples. Owing to more DMATCM exposed on the cement surface, the inhibition ring diameter produced by modified cement was improved to a maximum of 28.09 mm, and MC3T3-E1 cells performed the cell viabilities all beyond 70% and healthy adhesion after 72 h co-culturing. Taking all measured properties and ISO standards into account, the antibacterial bone cement under the ratio of 10% performed better, besides its good bactericidal effect, the other properties satisfied the requirements for clinical application.

Antibiotic-Loaded Ultrahigh Molecular Weight Polyethylenes.

The occurrence of periprosthetic joint infections (PJI) after total joint replacement constitutes a great burden for the patients and the healthcare system. Antibiotic-loaded polymethylmethacrylate (PMMA) bone cement is often used in temporary spacers during antibiotic treatment. PMMA is not a load-bearing solution and needs to be replaced by a functional implant. Elution from the ultrahigh molecular weight polyethylene (UHMWPE) bearing surface for drug delivery can combine functionality with the release of clinically relevant doses of antibiotics. In this study, the feasibility of incorporating a range of antibiotics into UHMWPE is investigated. Drug stability is assessed by thermo-gravimetric analysis and nuclear magnetic resonance spectroscopy. Drug-loaded UHMWPEs are prepared by compression molding, using eight antibiotics at different loading. The predicted intra-articular concentrations of drugs eluted from UHMWPE are above minimum inhibitory concentration for at least 3 weeks against Staphylococci, which are the major causative bacteria for PJI. The antibacterial efficacy is confirmed for samples covering 2% of a representative knee implant in vitro over 72 h, showing that a small fraction of the implant surface loaded with antibiotics may be sufficient against Staphylococci.

An injectable bioactive poly(γ-glutamic acid) modified magnesium phosphate bone cement for bone regeneration.

As potential alternatives for calcium phosphate bone cements, magnesium phosphate bone cements (MPC) have attracted considerable attention in recent years. However, their several defects, such as rapid setting times, highly hydration temperature and alkaline pH due to the part of the unreacted phosphate, restricted their applications in human body. With aim to overcome these defects, a novel polypeptite poly(γ-glutamic acid) (γ-PGA) modified MPC were developed. Effect of γ-PGA content on the injectability, anti-washout ability, setting times, hydration temperature, mechanical compressive strength, in vitro bioactivity and degradation were investigated. Moreover, in vitro cyto-compatibility was evaluated using MC3T3-E1 cells by CCK-8 and Live/Dead staining. All these results indicated that the 10%PGA-MPC with an improved handling performances, low hydration temperature, high mechanical compressive strength, and good cyto-compatibility hold a great potential for bone repair and regeneration.

The Effect of Povidone-Iodine Irrigation on the Efficacy of Antibiotic Cement In Vitro.

Povidone-iodine is a common antiseptic demonstrating success in reducing infection rates in primary arthroplasty; however, recent data suggest that its use in revision arthroplasty may increase infection rates. This study evaluated the effect of povidone-iodine solution on antibiotic cement and investigated the connection between povidone-iodine and increased infection rates in revision arthroplasty. Sixty antibiotic cement samples (ACSs) were formed using gentamicin-impregnated cement. The ACSs were divided into three groups: group A (n=20) was subject to a 3-minute povidone-iodine soak followed by a saline rinse; group B (n=20) underwent a 3-minute saline soak; and group C (n=20) underwent only a saline rinse. The antimicrobial activity of the samples was tested using a Kirby-Bauer-like assay using Staphylococcus epidermidis. The zone of inhibition (ZOI) was measured every 24 hours for 7 days. All groups possessed the greatest antimicrobial activity at 24 hours. Group C displayed a mass-corrected ZOI of 395.2 mm/g, which was statistically greater than the group B ZOI (313.2 mm/g, P<.05) but not the group A ZOI (346.5 mm/g, P>.05). All groups demonstrated a decrease in antimicrobial activity at 48 through 96 hours, with no significant difference at any time point. Prolonged soaking of antibiotic cement in a povidone-iodine or saline solution results in elution of the antibiotic into the irrigation solution, blunting initial antibiotic concentration. When using antibiotic cement, antiseptic soaks or irrigation should be focused prior to cementation. [Orthopedics. 2024;47(1):10-14.].

The effect of supplementing the calcium phosphate cement containing poloxamer 407 on cellular activities.

Calcium phosphate cement (CPC) is generally used for bone repair and augmentation. Poloxamers are tri-block copolymers that are used as surfactants but have applications in drug and antibiotic delivery. However, their biological effects on bone regeneration systems remain unelucidated. Here, we aimed to understand how supplementing the prototype CPC with poloxamer would impact cellular activity and its function as a bone-grafting material. A novel CPC, modified beta-tricalcium phosphate (mß-TCP) powder, was developed through a planetary ball-milling process using a beta-tricalcium phosphate (ß-TCP). The mß-TCP dissolves rapidly and accelerates hydroxyapatite precipitation; successfully shortening the cement setting time and enhancing the strength. Furthermore, the addition of poloxamer 407 to mß-TCP could reduce the risk of leakage from bone defects and improve fracture toughness while maintaining mechanical properties. In this study, the poloxamer addition effects (0.05 and 0.1 g/mL) on the cellular activities of MC3T3-E1 cells cultured in vitro were investigated. The cell viability of mß-TCP containing poloxamer 407 was similar to that of mß-TCP. All specimens showed effective cell attachment and healthy polygonal extension of the cytoplasm firmly attached to hydroxyapatite (HA) crystals. Therefore, even with the addition of poloxamer to mß-TCP, it does not have a negative effect to osteoblast growth. These data demonstrated that the addition of poloxamer 407 to mß-TCP might be considered a potential therapeutic application for the repair and regeneration of bone defects.

Multi-objective property optimisation of a phosphoserine-modified calcium phosphate cement for orthopaedic and dental applications using design of experiments methodology.

Phosphoserine is a ubiquitous molecule found in numerous proteins and, when combined with alpha-tricalcium phosphate (α-TCP) powder, demonstrates the ability to generate an adhesive biomaterial capable of stabilising and repairing bone fractures. Design of Experiments (DoE) approach was able to optimise the composition of phosphoserine-modified calcium phosphate cement (PM-CPC) demonstrating that the liquid:powder ratio (LPR) and quantity of phosphoserine (wt%) significantly influenced the handling, mechanical, and adhesion properties. Subsequently, the DoE optimisation process identified the optimal PM-CPC formulation, exhibiting a compressive strength of 29.2 ± 4.9 MPa and bond/shear strength of 3.6 ± 0.9 MPa after a 24 h setting reaction. Moreover, the optimal PM-CPC composition necessitated a mixing time of 20 s and displayed an initial setting time between 3 and 4 min, thus enabling homogenous mixing and precise delivery within a surgical environment. Notably, the PM-CPC demonstrated a bone-to-bone bond strength of 1.05 ± 0.3 MPa under wet conditions, coupled with a slow degradation rate during the first five days. These findings highlight the ability of PM-CPC to effectively support and stabilise bone fragments during the initial stages of natural bone healing. The developed PM-CPC formulations fulfil the clinical requirements for working and setting times, static mechanical, degradation properties, and injectability, enabling surgeons to stabilise complex bone fractures. This innovative bioinspired adhesive represents a significant advancement in the treatment of challenging bone injuries, offering precise delivery within a surgical environment and the potential to enhance patient outcomes. STATEMENT OF SIGNIFICANCE: This manuscript presents a noteworthy contribution to the field of bone fracture healing and fixation by introducing a novel phosphoserine-modified calcium phosphate cement (PM-CPC) adhesive by incorporating phosphoserine and alpha-TCP. This study demonstrates the fabrication and extensive characterisation of this adhesive biomaterial that holds great promise for stabilising and repairing complex bone fractures. Design of Experiment (DoE) software was used to investigate the correlations between process, property, and structure of the adhesive, resulting in a cost-effective formulation with desirable physical and handling properties. The PM-CPC adhesive exhibited excellent adhesion and cohesion properties in wet-field conditions. This research offers significant potential for clinical translation and contributes to the ongoing advancements in bone tissue engineering.

Evidence-Based Data Regarding the Use of Antibiotic-loaded Cement in Hip Arthroplasty. A bibliometric analysis of 50 years / Datos basados en la evidencia sobre el uso de cemento con antibióticos en la artroplastia de cadera. Análisis blbliométrico de 50 años

Introduction: The use of antibiotic-loaded cement is an intraoperative tool that has demonstrated potential benefits in hip arthroplasty. However, the global landscape of research on this topic remains unknown. The objective of this study was to analyze the scientific growth, characteristics, and metrics of global and historical research on the use of antibiotic-loaded cement in hip arthroplasty. Material and methods: A cross-sectional bibliometric study was conducted using Scopus as the data source. Results: A total of 523 documents published between 1973 and 2023 were selected. 89.9% (n=470) of the production consisted of original articles, with 11.85% being multi-center. 84.1% of the authors have published a single article, followed by 10.3% who have published two articles. Research has predominantly focused on adults or the elderly, with an emphasis on outcome evaluation (notably reoperation), assessing various antibiotic agents, and frequently employing retrospective designs. Conclusions: There has been a sustained increase in research on the use of antibiotic-loaded cement in hip arthroplasty over the last 50 years. The research trend has shifted towards the evaluation of adult or elderly patients, exploration of antimicrobial agents, techniques, and health outcomes, primarily using observational and retrospective designs. An emerging research-focus is the study of hip arthroplasty in rheumatoid arthritis patients. (AU)

Introducción: El uso de cemento cargado con antibiótico, es una herramienta intraoperatoria que ha demostrado potenciales beneficios en la artroplastia de cadera. Sin embargo, se desconoce el panorama global de la investigación sobre este tópico. El objetivo de este estudio fue analizar el crecimiento científico, características y métricas de la investigación global e histórica sobre el uso de cemento cargado con antibiótico en artroplastia de cadera. Material y métodos: Estudio bibliométrico de corte transversal, que utilizó como fuente de datos la base Scopus. Resultados: Se seleccionaron 523 documentos publicados entre 1973 y 2023. El 89,9% (n=470) de la producción consistió en artículos originales, siendo el 11,85% multicéntricos. El 84,1% de los autores han publicado un único artículo, seguido de un 10,3% que han publicado dos artículos. La investigación se ha centrado predominantemente en adultos o ancianos, con énfasis en la evaluación de resultados (especialmente la reoperación), evaluando diversos agentes antibióticos y empleando con frecuencia diseños retrospectivos. Conclusiones: En los últimos 50 años se ha producido un aumento sostenido de la investigación sobre el uso de cemento cargado con antibióticos en la artroplastia de cadera. La tendencia de la investigación se ha desplazado hacia la evaluación de pacientes adultos o ancianos, la exploración de los agentes antimicrobianos, las técnicas y los resultados sanitarios, utilizando principalmente diseños observacionales y retrospectivos. Un nuevo foco de investigación es el estudio de la artroplastia de cadera en pacientes con artritis reumatoide. (AU)

Octacalcium phosphate phase forming cements as an injectable bone substitute materials: Preparation and in vitro structural study.

In the realm of regenerating damaged or degenerated bones through minimally invasive techniques, injectable materials have emerged as exceptionally promising. Among these, calcium phosphate bone cements (CPCs) have garnered significant interest due to their remarkable bioactivity, setting it apart from non-degradable alternatives such as polymethyl methacrylate cements. α-Tricalcium phosphate (α-TCP) is a widely used solid phase component in CPCs. It can transform into calcium-deficient hydroxyapatite (CDHAp) when it comes in contact with water. In this study, we aimed to create an injectable, self-setting bone cement using low-temperature synthesized α-TCP powder as a single precursor of the powder phase. We found that changes in the pH of the liquid phase (pH 6.0, pH 6.2, pH 7.0 and pH 7.4) significantly altered the cement's setting, handling, and mechanical properties. The formation of the octacalcium phosphate (OCP) phase was identified in our study, which positively affects the osteoblastic cell response. Hardened OCP-forming bone cements prepared using a liquid phase with pH 7.0 and 7.4 showed better osteogenic cell attachment and proliferation than those prepared with pH 6.0 and 6.2. Our study suggests that changes in the pH of the liquid phase can significantly affect the properties of α-TCP-based bone cement, and the presence of the OCP phase is crucial for optimal cement performance.