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.

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.

A meta-analysis comparing the efficacy of mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cements in the treatment of vertebral compression fractures.

PURPOSE: Vertebral compression fractures are often treated with vertebroplasty, and filling the injured vertebrae with bone cement is a key part of vertebroplasty. This meta-analysis was performed to compare the clinical efficacy and safety of mineralized collagen-polymethylmethacrylate (MC-PMMA) and polymethylmethacrylate (PMMA) bone cement in the treatment of vertebral compression fractures by vertebroplasty. METHODS: A computerized search of the published literature on mineralized collagen-polymethylmethacrylate and polymethylmethacrylate bone cement in the treatment of vertebral compression fractures was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang database, PubMed, Embase, and Cochrane Library. The search was carried out from the time the database was created to March 2023 and 2 researchers independently conducted literature searches to retrieve a total of 884 studies, of which 12 were included in this meta-analysis. Cochrane systematic review methods were used to assess the quality of the literature and a meta-analysis was performed using ReviewManager 5.4 software. RESULTS: The results of the present meta-analysis showed that in postoperative adjacent vertebral fractures [OR = 0.25; 95% CI (0.15, 0.41)], postoperative cement leakage [OR = 0.45; 95% CI (0.30, 0.68)], Oswestry Disability Index (ODI) scores in the first 3 days after surgery [OR = -0.22; 95% CI (-0.42, -0.03)], ODI score at 6-12 months postoperatively [OR = -0.65; 95% CI (-0.97, -0.32)], visual analog scale (VAS) score at 6-12 months postoperatively [OR = -0.21; 95% CI (-0.46, 0.04)], and 1-year postoperative CT values [OR = 5.56; 95% CI (3.06, 8.06)], the MC-PMMA bone cement group was superior to the PMMA bone cement group. However, the differences between the two groups were not statistically different in terms of cement filling time, cement filling volume, operation time, intraoperative bleeding, hospitalization time, postoperative (<1 week, 3-6 months) vertebral body posterior convexity Cobb's angle, postoperative (<1 week, 6-12 months) vertebral body anterior margin relative height, postoperative (≤3 days, 1-3 months) pain VAS score and postoperative (1-3 months) ODI score. CONCLUSIONS: Compared with PMMA bone cement, the application of MC-PMMA bone cement is advantageous in reducing postoperative complications (adjacent vertebral fracture rate, cement leakage rate), pain relief, and functional recovery in the long-term postoperative period (>6 months), but there is still a need for more high-quality randomized controlled studies to provide more adequate evidence.

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.

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.

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.

Enhanced mechanic properties of calcium phosphate cements via mussel-inspired adhesive as bone substitute: Highlights of their interactions.

BACKGROUND: Inspired by natural bones, many organic components were added to Calcium Phosphate Cements (CPCs) to improve their mechanical strength. However, the strength of these composite CPCs is limited by the low strength of organic components itself and the weak interaction between organic components and CPCs. OBJECTIVE: Firstly, a composite CPC containing mussel-inspired adhesive, Poly-(Dopamine Methacrylamide-co-2-methoxy Ethylacrylate) (pDM) was developed. Secondly, the interactions between pDM and CPC and their effect on mechanical properties were investigated. METHODS: The interactions between pDM and CPC were performed by Nuclear Magnetic Resonance, Laser Raman, X-ray Photoelectron Spectroscopy, Fourier Transform-Infrared Spectroscopy and X-ray Diffraction Analysis. RESULTS: The toughness and compressive strength of pDM-CPC scaffold were both significantly enhanced, because of the enhanced interface binding strength among CPC and pDM due to their interaction and the improved mechanical strength of pDM owing to its self-oxidation cross-linking. The toughness of pDM-CPC scaffolds increased with the increased contents of pDM, while pDM-CPC scaffold containing 35 wt.% pDM had the highest compressive strength of all, which the latter was more than five times compared to that of CPC. CONCLUSION: The mechanically strong pDM-CPC scaffolds has potential application in bone regeneration as well as in craniofacial and orthopedic repair.

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.

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.

Effect of surface modification of graphene oxide with a reactive silane coupling agent on the mechanical properties and biocompatibility of acrylic bone cements.

Carbon allotrope materials (i.e. carbon nanotubes (CNTs), graphene, graphene oxide (GO)), have been used to reinforce acrylic bone cement. Nevertheless, the intrinsic incompatibility among the above materials produces a deficient interphase. Thus, in this work, the effect of the content of functionalized graphene oxide with a reactive silane on the mechanical properties and cell adhesion of acrylic bone cement was studied. GO was obtained by an oxidative process on natural graphite; subsequently, GO was functionalized with 3-methacryloxypropyltrimethoxysilane (MPS) to enhance the interphase between the graphenic material and acrylic polymeric matrix. Pristine GO and functionalized graphene oxide (GO-MPS) were characterized physicochemically (XPS, XRD, FTIR, and Raman) and morphologically (SEM and TEM). Silanized GO was added into the acrylic bone cement at different concentrations; the resulting materials were characterized mechanically, and their biocompatibility was also evaluated. The physicochemical characterization results showed that graphite was successfully oxidized, and the obtained GO was successfully functionalized with the silane coupling agent (MPS). SEM and TEM images showed that the GO is composed of few stacked layers. Compression testing results indicated a tendency of increasing stiffness and toughness of the acrylic bone cements at low concentration of functionalized GO. Additionally, the bending testing results showed a slightly increase in bone cement strain with the incorporation of GO-MPS. Finally, all samples exhibited cell viability higher than 70%, which means that materials are considered non-cytotoxic, according to the ISO 10993-5 standard.

Overcoming the Dilemma of In Vivo Stable Adhesion and Sustained Degradation by the Molecular Design of Polyurethane Adhesives for Bone Fracture Repair.

Bone adhesive is a promising candidate to revolutionize the clinical treatment of bone repairs. However, several drawbacks have limited its further clinical application, such as unreliable wet adhesive performance leading to fixation failure and poor biodegradability inhibiting bone tissue growth. By incorporating catechol groups and disulfide bonds into polyurethane (PU) molecules, an injectable and porous PU adhesive is developed with both superior wet adhesion and biodegradability to facilitate the reduction and fixation of comminuted fractures and the subsequent regeneration of bone tissue. The bone adhesive can be cured within a reasonable time acceptable to a surgeon, and then the wet bone adhesive strength is near 1.30 MPa in 1 h. Finally, the wet adhesive strength to the cortical bone will achieve about 1.70 MPa, which is also five times more than nonresorbable poly(methyl methacrylate) bone cement. Besides, the cell culture experiments also indicate that the adhesives show excellent biocompatibility and osteogenic ability in vitro. Especially, it can degrade in vivo gradually and promote fracture healing in the rabbit iliac fracture model. These results demonstrate that this ingenious bone adhesive exhibits great potential in the treatment of comminuted fractures, providing fresh insights into the development of clinically applicable bone adhesives.

Implications of ageing effects on thermal and mechanical properties of PMMA-based bone cement for THA revision surgery.

Loosening and infection are the main reasons for revision surgery in total hip arthroplasty (THA). Removing partially detached cemented implant components during revision surgery remains challenging and poses the risk of periprosthetic bone damage. A promising approach for a gentler removal of partially detached prostheses involves softening the PMMA-based bone cement by heating it above its glass transition temperature (TG), thus loosening the implant-cement bond. It is assumed that the TG of PMMA-based bone cement decreases in-vivo due to the gradual absorption of body fluid. Reliable data on TG are essential to develop a heat-based method for removing cemented implant components during revision surgery. The effect of water absorption was investigated in-vitro by ageing PMMA-based bone cement samples for different periods up to 56 days in both Ringer's solution (37 °C) and air (37 °C and 30% humidity). Subsequently, the TG and Vicat softening temperatures of the samples were determined by differential scanning calorimetry and Vicat tests, respectively, according to prescribed methods. Over the entire ageing period, i.e. comparing one day of ageing in air and 56 days in Ringer's solution, the Vicat softening temperature dropped by 16 °C, while the TG dropped by 10 °C for Palacos® R PMMA-based bone cement. Water absorption over time correlated significantly with the Vicat softening temperature until saturation of the PMMA-based bone cement was reached. Based on the TG and Vicat softening temperature measurements, it can be assumed that in body-aged bone cement, an optimal softening can be achieved within a temperature range of 85 °C-93 °C to loosen the bond between the PMMA-based bone cement mantle and the prosthesis stem. These findings may pave the way for a gentler removal of the implant in revision THA.

Enhanced Degradability of the Apatite-Based Calcium Phosphate Cement Incorporated with Amorphous MgZnCa Alloy.

Degradability is vital for bone filling and plays an important role in bone regeneration. Evidence indicates that apatite-based calcium phosphate cement (ACPC) is a prospective biomaterial for bone repair with enhanced osteogenesis. However, poor degradability restricts their clinical application. In this study, MgZnCa-doped ACPC (MgZnCa/ACPC) composites were fabricated by adding 3 (wt) % amorphous MgZnCa powder in the solid phase of ACPC to enhance the biodegradation and bioactivity of the apatite ACPC. The chemical and the physical properties of the MgZnCa/ACPC composite were investigated and compared with the ACPC composite. The results showed that the incorporation of MgZnCa improved both the degradability and the compressive strength of the ACPC composite. X-ray diffraction and Fourier transform infrared spectrometry analysis suggested significant changes in the microstructures of the composites due to the incorporation and the anodic dissolution of MgZnCa alloy. These findings indicate that the MgZnCa/ACPC composite is capable of facilitating bone repair and regeneration by endowing favorable degradation property.

Novel bone cement based on calcium phosphate composited CNT curcumin with improved strength and antitumor properties.

In this study, carboxylated carbon nanotube (CNT)-loaded curcumin (CUR) was blended into calcium phosphate cement (CPC) owing to the poor mechanical properties and single function of CPC as a bone-filling material, and CNT-CUR-CPC with improved strength and antitumor properties was obtained. The failure strength, hydrophilicity, in vitro bioactivity, bacteriostatic activity, antitumor activity, and cell safety of CNT-CUR-CPC were evaluated. The experimental results indicated that the failure strength of CNT-CUR-CPC increased from 25.05 to 45.05 MPa (p < 0.001) and its contact angle decreased from 20.37° to 15.27° (p < 0.001) after the CNT-CUR complex was added into CPC at the rate of 5 wt% and blended. Following soaking in simulated body fluid (m-SBF), the main components of CNT-CUR-CPC were hydroxyapatite (HA) and carbonate hydroxyapatite (HCA). The incorporation of CNT-CUR was beneficial for the deposition of PO43- and CO32-, and it promoted the crystallization of HA and HCA. For CNT-CUR-CPC, the inhibition zone diameter on Staphylococcus aureus was 10.2 ± 1.02 mm (p < 0.001) and it exhibited moderate sensitivity, whereas the inhibition zone diameter on Escherichia coli was 8.3 ± 0.23 mm (p < 0.001) and it exhibited low sensitivity. When compared with the CPC, the cell proliferation rate (RGR %) of the CNT-CUR-CPC decreased by 7.73% (p > 0.05) at 24 h, 17.89% (p < 0.05) at 48 h, and 24.43% (p < 0.001) at 72 h when MG63 cells were cultured on it. In particular, after the MG63 cells were cultured with the CNT-CUR-CPC for 48 h, the number of newly proliferating MG63 cells was significantly reduced, and their growth and adhesion on the surface of the CNT-CUR-CPC were inhibited when compared with the CPC. When 3T3-E1 cells were exposed to the m-SBF immersion solution of CNT-CUR-CPC, the cell proliferation rate (RGR %) was ≥80% (p > 0.05) and the cytotoxicity grade was 0-1. The 3T3-E1 cells were cultured with the m-SBF soaking solution of CNT-CUR-CPC for 24 h, and no significant changes in cell morphology or cytotoxicity were observed. After the 3T3-E1 cells were cultured on CNT-CUR-CPC for 48 h, they could stick to and grow on its surface without adverse reactions. CNT-CUR-CPC had a hemolysis rate of 4.3% (p > 0.05) and did not result in hemolysis and hemagglutination. The obtained CNT-CUR-CPC scaffold material exhibited effective antibacterial activity and cell safety, and could achieve a certain antitumor effect, which has a wide application potential in bone tissue engineering.

Injectable Self-Harden Antibiofilm Bioceramic Cement for Minimally Invasive Surgery.

There is an urgent demand for antibacterial bone grafts in clinics. Worryingly, the misuse and overuse of antibiotics accelerate the emergence of drug-resistant bacteria. Therefore, this study prepared a novel injectable bioceramic cement without antibiotics (FS-BCS), which showed good antibacterial properties by loading iron and strontium onto a matrix composed of brushite and calcium sulfate. The setting time, injectability, microstructure, antibacterial properties, anti-biofilm properties, and cytocompatibility of the novel bioceramic cement were evaluated thoroughly. The results showed that the material was highly injectable and antiwashout. The antibacterial tests revealed that FS-BCS inhibited the growth of 99.9% E. coli and S. aureus separately in the broth due to the synergistic effect of strontium and iron. Simultaneously, crystal violet and fluorescent staining tests revealed that the material could significantly inhibit the formation of E. coli and S. aureus biofilms. In addition, the co-incorporation of iron and strontium promoted the proliferation and migration of osteoblasts. Therefore, FS-BCS has good application potential in antibiotic-free anti-infection bone grafting using minimally invasive surgery.

[Chemical and physical properties of PMMA bone cements]. / Chemische und physikalische Eigenschaften von PMMA-Knochenzementen.

PMMA-based bone cements are used for anchoring artificial joints. The cements are offered as two-component systems. During mixing, a liquid paste is formed by free-radical polymerization, which completely hardens into a solid cement matrix as polymerization progresses with an increase in viscosity. Polymerization from MMA to PMMA is an exothermic process, energy is released in the form of heat. After fixation of the prosthesis and curing of the cement, the cement fills the space between the prosthesis and the bone. With the filler PMMA, a strong force-locking and interlocking mechanical bond is created. The essential properties of PMMA cements are dictated by the powder component. In vivo, the hard and brittle bone cements absorb body fluids and become more elastic and softer. The properties of various PMMA bone cements differ significantly, although the chemical acrylate base is identical.

Effects of Zinc and Strontium Doping on In Vitro Osteogenesis and Angiogenesis of Calcium Silicate/Calcium Phosphate Cement.

Based on multiple biological functions (mainly osteogenesis and angiogenesis) of bioactive ions, Zn/Sr-doped calcium silicate/calcium phosphate cements (Zn/Sr-CS/CPCs, including 10Zn-CS/CPC, 20Sr-CS/CPC, and 10Zn/20Sr-CS/CPC) were prepared by the addition of Zn and Sr dual active ions into CS/CPC to further accelerate its bone regeneration in this study. The physicochemical and biological properties of the Zn/Sr-CS/CPCs were systematically investigated. The results showed that the setting time was slightly prolonged, the compressive strength and porosity did not change much, and all groups maintained good injectability after the doping of Zn and Sr. Besides, the doping of Zn and Sr had little effect on the phase and microstructure of hydrated products of CS/CPC. The degradation rate of Zn/Sr-CS/CPCs decreased after doping with Zn and Sr. In mouse bone marrow mesenchymal stem cells (mBMSC) experiments, all Zn/Sr-CS/CPCs stimulated the viability, adhesion, proliferation, and alkaline phosphatase (ALP) activity together with osteogenesis-related genes (ALP, Runx2, Col-I, OCN, and OPN). The further addition of Zn and Sr played better and synergistic roles in in vitro osteogenesis. Thereinto, 10Zn/20Sr-CS/CPC manifested the optimum in vitro osteogenic performance. As for human umbilical vein endothelial cell (HUVEC) experiments, the incorporation of CS doped with Zn and Sr into CPC possessed good vascularization properties of proliferation, NO secretion, tube formation, and the expression of angiogenesis-related genes (VEGF, bFGF, and eNOS). In conclusion, the doping of Zn and Sr into CS/CPC could exhibit excellent osteogenesis and good angiogenesis potentials and 10Zn/20Sr-CS/CPC could be considered as a promising candidate in bone repair.

The self-regulating on cohesion properties of calcium phosphate/ calcium sulfate bone cement improved by citric acid/sodium alginate.

Calcium phosphate cement (CPC) has attracted extensive interest from surgeons and materials scientists. However, the collapsibility of calcium phosphate cement limits its clinical application. In this work, a gel network of SA-CA formed by the reaction of citric acid (CA) and sodium alginate (SA) was introduced into the α-TCP/α-CSH composite. Furthermore, a high proportion of α-CSH provided more calcium sources for the system to combine with SA forming a gel network to improve the cohesion property of the composite, which also played a regulating role in the conversion of materials to HA. The morphology, physicochemical properties, and cell compatibility of the composites were studied with SA-CA as curing solution. The results show that SA-CA plays an important role in the compressive strength and collapse resistance of bone cement, and its properties can be regulated by changing the content of CA. When CA is 10 wt%, the mechanical strength is the highest, reaching 12.49 ± 2.03 MPa, which is 265.80% higher than water as the solidifying liquid. In addition, the cell experiments showed that the samples were not toxic to MC3T3 cells. The results of ALP showed that when SA-CA were used as curing solution, the activity of ALP was higher than that of blank sample, indicating that the composite bone cement could be conducive to the differentiation of osteoblasts. In this work, the α-CSH/α-TCP based composite regulated by gel network of SA-CA can provide a promising strategy to improve the cohesion of bone cement.

Calcium phosphate cement with minocycline hydrochloride-loaded gelatine microspheres for peri-implantitis treatment.

OBJECTIVES: This study aimed to fabricate an antibacterial calcium phosphate cement (CPC) with minocycline hydrochloride (MINO)-loaded gelatine microspheres (GMs) as a local drug delivery system for the treatment of peri­implantitis. METHODS: CPC/GMs(MINO), incorporating MINO-loaded GMs into CPC, was developed and characterised using scanning electron microscopy (SEM), X-ray diffraction (XRD), and drug release profiling. The antibacterial activity against Porphyromonas gingivalis and Fusobacterium nucleatum was evaluated. Bone mesenchymal stem cells (BMSCs) were cultured in the extracts of the developed cements to evaluate osteoinductivity in vitro. Furthermore, a rabbit femoral model was established to evaluate osteogenic ability in vivo. RESULTS: SEM and XRD confirmed the porous structure and chemical stability of CPC/GMs(MINO). The release profile showed a sustained release of MINO from CPC/GMs(MINO), reaching an equilibrium state on the 14th day with a cumulative release ratio of approximately 84%. For antibacterial assays, the inhibition zone of CPC/GMs(MINO) was 3.67 ± 0.31 cm for P. gingivalis and 7.47 ± 0.50 cm for F. nucleatum. Most bacteria seeded on CPC/GMs(MINO) died after 24 h of culture. In addition, CPC/GMs(MINO) significantly enhanced alkaline phosphatase activity, osteogenic gene expression, and BMSC mineralisation compared with CPC/GMs and the control group (P < 0.05). The in vivo results showed that CPC/GMs(MINO) possessed a higher quality and quantity of bone formation and maturation than CPC/GMs and CPC. CONCLUSIONS: CPC/GMs(MINO) showed excellent antibacterial activity against pathogens associated with peri­implantitis and demonstrated good osteoinductivity and osteogenic ability. CLINICAL SIGNIFICANCE: Peri-implantitis is among the most common and challenging biological complications associated with dental implants. In this study, MINO-loaded GMs were incorporated into CPC, which endowed the composite cement with excellent antibacterial and osteogenic abilities, demonstrating its potential as a bone graft substitute for treating peri­implantitis.