Β-tricalcium Phosphate Research Articles

Smurf1-targeting microRNA-136-5p-modified bone marrow mesenchymal stem cells combined with 3D-printed β-tricalcium phosphate scaffolds strengthen osteogenic activity and alleviate bone defects.

Suitable biomaterials with seed cells have promising potential to repair bone defects. However, bone marrow mesenchymal stem cells (BMSCs), one of the most common seed cells used in tissue engineering, cannot differentiate efficiently and accurately into functional osteoblasts. In view of this, a new tissue engineering technique combined with BMSCs and scaffolds is a major task for bone defect repair. Lentiviruses interfering with miR-136-5p or Smurf1 expression were transfected into BMSCs. The effects of miR-136-5p or Smurf1 on the osteogenic differentiation (OD) of BMSCs were evaluated by measuring alkaline phosphatase activity and calcium deposition. Then, the targeting relationship between miR-136-5p and Smurf1 was verified by bioinformatics website analysis and dual luciferase reporter assay. Then, a rabbit femoral condyle bone defect model was established. miR-136-5p/BMSCs/β-TCP scaffold was implanted into the defect, and the repair of the bone defect was detected by Micro-CT and HE staining. Elevating miR-136-5p-3p or suppressing Smurf1 could stimulate OD of BMSCs. miR-136-5p negatively regulated Smurf1 expression. Overexpressing Smurf1 reduced the promoting effect of miR-136-5p on the OD of BMSCs. miR-136-5p/BMSCs/β-TCP could strengthen bone density in the defected area and accelerate bone repair. SmurF1-targeting miR-136-5p-modified BMSCs combined with 3D-printed β-TCP scaffolds can strengthen osteogenic activity and alleviate bone defects.

3D Printed Multifunctional Biomimetic Bone Scaffold Combined with TP-Mg Nanoparticles for the Infectious Bone Defects Repair.

Infected bone defects are one of the most challenging problems in the treatment of bone defects due to the high antibiotic failure rate and the lack of ideal bone grafts. In this paper, inspired by clinical bone cement filling treatment, α-c phosphate (α-TCP) with self-curing properties is composited with β-tricalcium phosphate (β-TCP) and constructed a bionic cancellous bone scaffolding system α/β-tricalcium phosphate (α/β-TCP) by low-temperature 3D printing, and gelatin is preserved inside the scaffolds as an organic phase, and later loaded with a metal-polyphenol network structure of tea polyphenol-magnesium (TP-Mg) nanoparticles. The scaffolds mimic the structure and components of cancellous bone with high mechanical strength (>100MPa) based on α-TCP self-curing properties through low-temperature 3D printing. Meanwhile, the scaffolds loaded with TP-Mg exhibit significant inhibition of Staphylococcus aureus (S.aureus) and promote the transition of macrophages from M1 pro-inflammatory to M2 anti-inflammatory phenotype. In addition, the composite scaffold also exhibits excellent bone-enhancing effects based on the synergistic effect of Mg2+ and Ca2+. In this study, a multifunctional ceramic scaffold (α/β-TCP@TP-Mg) that integrates anti-inflammatory, antibacterial, and osteoinduction is constructed, which promotes late bone regenerative healing while modulating the early microenvironment of infected bone defects, has a promising application in the treatment of infected bone defects.

Controlled anticancer 5-Fluorouracil release from functionalized 5-FU/PLGA/CaP coating on titanium implants: Characterization, in vitro drug delivery and cytotoxicity

Work presents a novel approach for creating anticancer coatings on titanium implants using 5-Fluorouracil (5-FU) loaded in calcium phosphate which is encapsulated in poly(lactic-co-glycolic acid) (PLGA/CaP) for controllable drug release. Our method involves the hybrid ultrasound-assisted micro-arc oxidation (UMAOH) technique, which make use of an ultrasound as an additional means of energy input resulting in increased pore size, drug deposition, and layer-by-layer self-assembly of PLGA. The multilayer coatings exhibit amorphous-crystalline structure with dicalcium phosphate anhydrous (DCPA) and β-tricalcium phosphate (β-TCP) phases, Ca/P ratio of 0.3, surface roughness (Ra) of 2.3–3.5 µm, and thickness between 52–60 µm. Drug release kinetics revealed a burst release for 5FU/CaP in the initial 10–20 min and sustained release over 2–4 h. 5FU/PLGA/CaP displayed a smooth, sustained release over 5 days. Biocompatibility studies showed that extracts from drug-free CaP and CaP/PLGA samples were nontoxic to HeLa, NIH-3Т3, and MCF-7 cell lines (≥ 80 % cell viability) for 0.2–24 h. In contrast, extracts from drug-loaded carriers were cytotoxic to NIH-3T3 cells (> 60 % cell death). Notably, 5-FU impregnation in the CaP coting demonstrated varying cytotoxicity, with the following cell death order: 75 % HeLa > 68 % NIH-3Т3 > 59 % MCF-7. PLGA modification reduced cytotoxicity with the following cell death order: 61 % HeLa > 52 % NIH-3Т3 > 46 % MCF-7. This work presents a promising strategy for localized, controlled drug delivery 5FU/PLGA/CaP system, with reduced cytotoxicity compared to PLGA-free 5-FU/CaP coating, advancing implant-based cancer treatment.

Evaluation of β-tricalcium Phosphate (β-TCP) and Platelet Rich Plasma (PRP) Combination for Fracture Healing in Dogs Stabilized with Intramedullary Pinning

Background: The use of synthetic bone substitute,b-tricalcium phosphate (β-TCP) as an osteo-conductive material and platelet-rich plasma (PRP) as an osteo-inductive material is the alternate strategies for replenishing bone loss. Thus, the present study was conducted to evaluate the bone healing efficacy of β-TCP and PRP combination in dogs with long bone fracture repaired with threaded intramedullary pinning. Methods: Fifteen dogs were selected, which were allotted to two groups irrespective of age, breed and sex. In six dogs of Group I intramedullary pinning was performed, while in nine dogs of Group II β-TCP and PRP was applied at fracture site after stabilising with intramedullary pin. Clinical and radiographic examinations were conducted preoperatively and postoperatively on 15th, 30th and 60th day. Result: The mean weight bearing and radiographic union scores were better in group II animals as compared to group I at different time intervals. The present findings suggest that β-TCP and PRP effectively enhances the bone healing in dogs with long bone fracture.

β-tricalcium phosphate enhanced biomineralization of Cd2+ and Pb2+ by Sporosarcina ureilytica HJ1 and Sporosarcina pasteurii HJ2

Microbiologically induced CaCO3 precipitation (MICP) has been proposed as a potential bioremediation method to immobilize contaminating metals. In this study, carbonate mineralizing bacteria HJ1 and HJ2, isolated from heavy metal contaminated soil, was employed for Cd2+ and Pb2+ immobilization with or without β-tricalcium phosphate addition. Compared with the only treatments amended with strains, the combined application of β-tricalcium phosphate and HJ1 improved the immobilization rates of Cd and Pb by 1.49 and 1.70 times at 24 h, and the combined application of β-tricalcium phosphate and HJ2 increased the immobilization rates of Cd and Pb by 1.25 and 1.79 times. The characterization of biomineralization products revealed that Cd2+ and Pb2+ primarily immobilized from the liquid phase as CdCO3 and PbCO3, and the addition of β-tricalcium phosphate facilitated the formation of Ca4.03Cd0.97(PO4)3(OH) and Pb3(PO4)2. Also, the calcium source was related to the speciation of carbonate precipitation and improved the Cd and Pb remediation efficiency. This research demonstrated the feasibility and effectiveness of MICP combined with β-tricalcium phosphate in immobilization of Cd and Pb, which will provide a fundamental basis for future applications of MICP to mitigate soil heavy metal pollutions.

Characterization of Porous β-Type Tricalcium Phosphate Ceramics Formed via Physical Foaming with Freeze-Drying.

Porous β-tricalcium phosphate (Ca3(PO4)2; β-TCP) was prepared via freeze-drying and the effects of this process on pore shapes and sizes were investigated. Various samples were prepared by freezing β-TCP slurries above a liquid nitrogen surface at -180 °C with subsequent immersion in liquid nitrogen at -196 °C. These materials were then dried under reduced pressure in a freeze-dryer, after which they were sintered with heating. Compared with conventional heat-based drying, the resulting pores were more spherical, which increased both the mechanical strength and porosity of the β-TCP. These materials had a wide range of pore sizes from 50 to 200 µm, with the mean and median values both approximately 100 µm regardless of the freeze-drying conditions. Mercury porosimetry data showed that the samples contained small, interconnected pores with sizes of 1.24 ± 0.25 µm and macroscopic, interconnected pores of 25.8 ± 4.7 µm in size. The effects of nonionic surfactants having different hydrophilic/lipophilic balance (HLB) values on foaming and pore size were also investigated. Materials made with surfactants having lower HLB values exhibited smaller pores and lower porosity, whereas higher HLB surfactants gave higher porosity and slightly larger macropores. Even so, the pore diameter could not be readily controlled solely by adjusting the HLB value. The findings of this work indicated that high porosity (>75%) and good compressive strength (>2 MPa) can both be obtained in the same porous material and that foaming agents with HLB values between 12.0 and 13.5 were optimal.

A 3D In-vitro model of the human dentine interface shows long-range osteoinduction from the dentine surface

Emerging regenerative cell therapies for alveolar bone loss have begun to explore the use of cell laden hydrogels for minimally invasive surgery to treat small and spatially complex maxilla-oral defects. However, the oral cavity presents a unique and challenging environment for in vivo bone tissue engineering, exhibiting both hard and soft periodontal tissue as well as acting as key biocenosis for many distinct microbial communities that interact with both the external environment and internal body systems, which will impact on cell fate and subsequent treatment efficacy. Herein, we design and bioprint a facile 3D in vitro model of a human dentine interface to probe the effect of the dentine surface on human mesenchymal stem cells (hMSCs) encapsulated in a microporous hydrogel bioink. We demonstrate that the dentine substrate induces osteogenic differentiation of encapsulated hMSCs, and that both dentine and β-tricalcium phosphate substrates stimulate extracellular matrix production and maturation at the gel-media interface, which is distal to the gel-substrate interface. Our findings demonstrate the potential for long-range effects on stem cells by mineralized surfaces during bone tissue engineering and provide a framework for the rapid development of 3D dentine-bone interface models.

Vat photopolymerization of biomimetic bone scaffolds based on Mg, Sr, Zn-substituted hydroxyapatite: Effect of sintering temperature

In response to the urgent demand for innovative bone regeneration solutions, the focus of this study is to develop and characterize Mg, Sr, Zn-substituted calcium phosphate scaffolds that replicate the trabecular architecture of cancellous bone. Ion substitution represents a promising approach to improve the biological effectiveness of calcium phosphates and composite materials used in bone tissue engineering applications. Porous scaffolds mimicking the natural bone structure were additively manufactured from the photosensitive ceramic suspensions for vat photopolymerization using digital light processing. The impact of the selected trace elements (0, 1 and 5 mol.% substitution) and the sintering temperature (900, 1000, 1100, 1200, and 1300 °C) was investigated in relation to the obtained crystalline phase content, microstructure, elemental distribution, thermal stability, and mechanical properties. After sintering, in addition to hydroxyapatite, β-tricalcium phosphate was detected as a result of the added trace elements in the calcium-deficient hydroxyapatite used as a starting powder. The obtained scaffolds exhibited uniform distribution of the trace elements, and they feature 3D-designed porosity predominantly ranged from 10 to 900 μm in diameter, with an average pore size of 546.25 ± 10.95 μm. The total porosity of scaffolds was 76.24 ± 1.32 vol% and an average wall thickness of 217.03 ± 8.98 μm, closely resembling the morphology of cancellous bone tissue. The mechanical properties of the scaffolds sintered at 1100 °C, 1200 °C, and 1300 °C were in line with those typically observed in trabecular bone. The study demonstrates the feasibility of using custom made bioactive hydroxyapatite powders together with vat photopolymerization to design the porosity and properties of the bone scaffolds on demand, based on the requirements of individual bone defects.

Novel injectable composite incorporating denosumab promotes bone regeneration via bone homeostasis regulation

Repair of large bone defects remains to be clinically challenging, yet current bone repair strategies focus on optimizing the osteogenic capacity of bone grafts, while the role of osteoclasts in bone regeneration has been largely ignored. Herein, we designed a injectable self-curing bone grafting paste capable of regulating both anabolic/catabolic activities during bone healing by immobilizing the RANKL inhibitor denosumab on dermal-derived extracellular matrix (ECM) microfibres, which were then incorporated into an injectable paste via a hydration reaction between β-tricalcium phosphate (β-TCP), monocalcium phosphate monohydrate (MCPM) and calcium sulfate hemihydrate (CSH). The incorporation of ECM microfibres not only serves as a sustained-release denosumab carrier to inhibit osteoclastogenesis but also improves the mechanical properties of the resulting composite by increasing the interaction between the organic and inorganic phases. In vitro, calcium supply from the composite along with ECM enhanced osteogenic differentiation of BMSC while release of denosumab effectively inhibits osteoclast fusion and alleviate osteoclastic activity. In vivo, it was observed that CSH/CP@ECM-Deno significantly reduced the number of osteoclasts, slowed down the process of bone resorption, and accelerated collagen deposition to promote new bone generation. These results suggest that modulation of osteoclastogenesis by interfering with bone homeostasis may be an effective bone repair strategy.

Nonoperative and Operative Soft-Tissue, Cartilage, and Bony Regeneration and Orthopaedic Biologics of the Elbow and Upper Extremity: An Orthoregeneration Network Foundation Review

Orthoregeneration is defined as a solution for orthopaedic conditions that harnesses the benefits of biology to improve healing, reduce pain, improve function, and, optimally, provide an environment for tissue regeneration. Options include drugs, surgical intervention, scaffolds, biologics as a product of cells, and physical and electromagnetic stimuli. The goal of regenerative medicine is to enhance the healing of tissue after musculoskeletal injuries as both isolated treatment and adjunct to surgical management, using novel therapies to improve recovery and outcomes. Various orthopaedic biologics (orthobiologics) have been investigated for the treatment of pathology involving the elbow and upper extremity, including the tendons (lateral epicondylitis, medial epicondylitis, biceps tendonitis, triceps tendonitis), articular cartilage (osteoarthritis, osteochondral lesions), and bone (fractures, nonunions, avascular necrosis, osteonecrosis). Promising and established treatment modalities include hyaluronic acid; botulinum toxin; corticosteroids; leukocyte-rich and leukocyte-poor platelet-rich plasma; autologous blood; bone marrow aspirate comprising mesenchymal stromal cells (alternatively termed medicinal signaling cells and frequently mesenchymal stem cells [MSCs]) and bone marrow aspirate concentrate; MSCs harvested from adipose and skin (dermis) sources; vascularized bone grafts; bone morphogenic protein scaffold made from osteoinductive and conductive β-tricalcium phosphate and poly-ε-caprolactone with hydrogels, human MSCs, and matrix metalloproteinases; and collagen sponge. Autologous blood preparations such as autologous blood injections and platelet-rich plasma show positive outcomes for nonresponsive tendinopathy. In addition, cellular therapies such as tissue-derived tenocyte-like cells and MSCs show a promising ability to regulate degenerative processes by modulating tissue response to inflammation and preventing continuous degradation and support tissue restoration.

Histological Bone-Healing Evaluation of Critical-Size Defects Filled with β-Tricalcium Phosphate in Rat Tibiae

Bone defects may be a result of different pathologies and represent a challenge in different fields of dentistry. Techniques for the correction of bone defects involving the use of several types of grafts have been proposed. This study evaluated bone repair in rat tibiae after surgically created critical-size defects were filled with β-tricalcium phosphate (RTR®, Septodont, FR). Critical-size bone defects were created in the tibiae of 32 male Wistar rats, which were divided into four groups (n = 8): Control 30 days, Control 90 days, RTR® 30 days, and RTR® 90 days. After the experimental period, the animals were euthanized and specimens were collected, embedded in paraffin, serially cut, and stained with hematoxylin and eosin to evaluate the inflammatory and repair response. Two parameters were analyzed: neoformed bone tissue areas (NBA) and neoformed cortical areas (NCA). Statistical analysis was performed by ANOVA and Tukey’s test (p < 0.05). The RTR® group demonstrated superior bone healing compared with the control group in both analyzed parameters (NBA and NCA), with repair of the cortical bone and bone-tissue formation in the central region of the defect, which showed partial repair in the defect area (p < 0.05). RTR® enhanced bone neoformation in the adopted experimental model and may be a useful biomaterial to boost healing in cases of critical-size bone defects.

Polycaprolactone/β-Tricalcium Phosphate Composite Scaffolds with Advanced Pore Geometries Promote Human Mesenchymal Stromal Cells' Osteogenic Differentiation.

Critical-sized mandibular bone defects, arising from, for example, resections after tumor surgeries, are currently treated with autogenous bone grafts. This treatment is considered very invasive and is associated with limitations such as morbidity and graft resorption. Tissue engineering approaches propose to use 3D scaffolds that combine structural features, biomaterial properties, cells, and biomolecules to create biomimetic constructs. However, mimicking the complex anatomy and composition of the mandible poses a challenge in scaffold design. In our study, we evaluated the dual effect of complex pore geometry and material composition on the osteogenic potential of 3D printed scaffolds. The scaffolds were made of polycaprolactone (PCL) alone (TCP0), or with a high concentration of β-tricalcium phosphate (β-TCP) up to 40% w/w (TCP40), with two complex pore geometries, namely a star- (S) and a diamond-like (D) shape. Scanning electron microscopy and microcomputed tomography images confirmed high fidelity during the printing process. The D-scaffolds displayed higher compressive moduli than the corresponding S-scaffolds. TCP40 scaffolds in simulated body fluid showed deposition of minerals on the surface after 28 days. Subsequently, we assessed the differentiation of seeded bone marrow-derived human mesenchymal stromal cells (hMSCs) over 28 days. The early expression of RUNX2 in the cell nuclei confirmed the commitment toward an osteogenic phenotype. Moreover, alkaline phosphatase (ALP) activity and collagen deposition displayed an increasing trend in the D-scaffolds. Collagen type I was mainly present in the deposited extracellular matrix (ECM), confirming deposition of bone matrix. Finally, Alizarin Red staining showed successful mineralization on all the TCP40 samples, with higher values for the S-shaped scaffolds. Taken together, our study demonstrated that the complex pore architectures of scaffolds comprised TCP40 stimulated osteogenic differentiation and mineralization of hMSCs in vitro. Future research will aim to validate these findings in vivo.

Formulation and Characterization of Chitosan-Based Mixed-Matrix Scaffold for Tissue Engineering

The use of scaffolds, three-dimensional porous, biodegradable and biocompatible structures, that can be produced from natural polymers, synthetics, ceramics and metals is crucial in the tissue engineering field. Chitosan is a polysaccharide of natural origin, found in the exoskeleton of marine arthropods and in the cell wall of fungi, with enormous popularity in the production of three-dimensional materials for Tissue Engineering, in particular bone repair. This polymer has several advantages in the production of these structures in bone regeneration and repair: biodegradability, biocompatibility, non-toxicity and antimicrobial properties. This study aimed to prepare porous scaffolds, for bone repair of degenerative diseases in the spine with better performance and less secondary effects, based on chitosan and another biopolymer (sodium alginate) with the incorporation of calcium phosphates (hydroxyapatite and β-tricalcium phosphate), for tissue engineering application. The obtained scaffolds were object of a detailed characterization, namely with regard to their porosity through the ethanol method, degradation, positron annihilation spectroscopy (PAS), mechanical properties, scanning electronic microscope (SEM), thermal stability through thermogravimetric analysis (TGA), chemical composition through X-ray diffraction (XRD) and Fourier transform infrared spectroscopy (FTIR). The results obtained showed that the different scaffolds presented pores able to support osteoid matrix growth. The crosslinking of scaffolds was also evaluated and resulted in pores with smaller dimensions and higher regularity in the chitosan-sodium alginate polymer without calcium phosphate scaffold. It was also possible to observe the effect of inorganics on mixed-matrix scaffolds, both morphologically and chemically. These scaffolds showed promising results in terms of mechanical and chemical properties, along with promising porosity for tissue regeneration applications.

Amorphization of β-tricalcium phosphate particles by mechanochemical treatment

Increasing the amounts of calcium and phosphate ions released in vivo by β-tricalcium phosphate (β-TCP) may enhance its osteogenic activity for bone repair and regeneration. Planetary ball milling of β-TCP powder using acetone and 1-mm-diameter zirconia beads reduced the average particle size of the powder to ∼ 0.4 µm within 120 min and converted most of the crystals to an amorphous phase of calcium orthophosphate. Immersing the treated powder in a tris-HCl buffered solution of pH 7.4 for 24 h at 37 °C dissolved calcium and phosphate ions with several times the yield from that of the original β-TCP powder. This approach is expected to be useful for preparing composite materials with an enhanced therapeutic effect on living tissues.

Strontium and Copper Co-Doped Multifunctional Calcium Phosphates: Biomimetic and Antibacterial Materials for Bone Implants.

β-tricalcium phosphate (β-TCP) is a promising material in regenerative traumatology for the creation of bone implants. Previously, it was established that doping the structure with certain cations can reduce the growth of bacterial activity. Recently, much attention has been paid to co-doped β-TCP, that is explained by their ability, on the one hand, to reduce cytotoxicity for cells of the human organism, on the other hand, to achieve a successful antibacterial effect. Sr, Cu-co-doped solid solutions of the composition Ca9.5-xSrxCu(PO4)7 was obtained by the method of solid-phase reactions. The Rietveld method of structural refinement revealed the presence of Sr2+ ions in four crystal sites: M1, M2, M3, and M4. The M5 site is completely occupied by Cu2+. Isomorphic substitution of Ca2+ → (Sr2+and Cu2+) expands the concentration limits of the existence of the solid solution with the β-TCP structure. No additional phases were formed up to x = 4.5 in Ca9.5-xSrxCu(PO4)7. Biocompatibility tests were performed on cell lines of human bone marrow mesenchymal stromal cells (hMSC), human fibroblasts (MRC-5) and osteoblasts (U-2OS). It was demonstrated that cytotoxicity exhibited a concentration dependence, along with an increase in osteogenesis and cell proliferation. Ca9.5-xSrxCu(PO4)7 powders showed significant inhibitory activity against pathogenic strains Escherichia coli and Staphylococcus aureus. Piezoelectric properties of Ca9.5-xSrxCu(PO4)7 were investigated. Possible ways to achieve high piezoelectric response are discussed. The combination of bioactive properties of Ca9.5-xSrxCu(PO4)7 renders them multifunctional materials suitable for bone substitutes.

Patient-specific implants made of 3D printed bioresorbable polymers at the point-of-care: material, technology, and scope of surgical application

BackgroundBioresorbable patient-specific additive-manufactured bone grafts, meshes, and plates are emerging as a promising alternative that can overcome the challenges associated with conventional off-the-shelf implants. The fabrication of patient-specific implants (PSIs) directly at the point-of-care (POC), such as hospitals, clinics, and surgical centers, allows for more flexible, faster, and more efficient processes, reducing the need for outsourcing to external manufacturers. We want to emphasize the potential advantages of producing bioresorbable polymer implants for cranio-maxillofacial surgery at the POC by highlighting its surgical applications, benefits, and limitations.MethodsThis study describes the workflow of designing and fabricating degradable polymeric PSIs using three-dimensional (3D) printing technology. The cortical bone was segmented from the patient’s computed tomography data using Materialise Mimics software, and the PSIs were designed created using Geomagic Freeform and nTopology software. The implants were finally printed via Arburg Plastic Freeforming (APF) of medical-grade poly (L-lactide-co-D, L-lactide) with 30% β-tricalcium phosphate and evaluated for fit.Results3D printed implants using APF technology showed surfaces with highly uniform and well-connected droplets with minimal gap formation between the printed paths. For the plates and meshes, a wall thickness down to 0.8 mm could be achieved. In this study, we successfully printed plates for osteosynthesis, implants for orbital floor fractures, meshes for alveolar bone regeneration, and bone scaffolds with interconnected channels.ConclusionsThis study shows the feasibility of using 3D printing to create degradable polymeric PSIs seamlessly integrated into virtual surgical planning workflows. Implementing POC 3D printing of biodegradable PSI can potentially improve therapeutic outcomes, but regulatory compliance must be addressed.

Use of Unidirectional Porous β-Tricalcium Phosphate in the Tibial Tunnel for Anterior Cruciate Ligament Reconstruction: A Case Series.

Bone defects in the tibial tunnel for anterior cruciate ligament (ACL) reconstruction can cause adverse events. The unidirectional porous tricalcium β-phosphate (UDPTCP) has the potential to be used as a filling substitute for bone defects. In this case series, we present the first nine cases in which UDPTCP was used as a bone substitute in the tibial tunnel during ACL reconstruction. The patients comprised six males and three females, with an average age of 32 years (range: 16-50 years). A cylindrical UDPTCP measuring 10 x 20 mm was molded to fit the tibial tunneland then implanted. At the one-year postoperative follow-up, none of the patients demonstrated any complications, and bone remodeling was observed on radiographs. Therefore, UDPTCP may provide a safe and reliable filling substitute for the tibial tunnel in ACL reconstruction.

Injectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute promotes bone regeneration by moderating oxidative stress in osteoporotic bone defect

The treatment of osteoporotic bone defect remains a big clinical challenge because osteoporosis (OP) is associated with oxidative stress and high levels of reactive oxygen species (ROS), a condition detrimental for bone formation. Anti-oxidative nanomaterials such as selenium nanoparticles (SeNPs) have positive effect on osteogenesis owing to their pleiotropic pharmacological activity which can exert anti-oxidative stress functions to prevent bone loss and facilitate bone regeneration in OP. In the current study a strategy of one-pot method by introducing Poly (lactic acid-carbonate) (PDT) and β-Tricalcium Phosphate (β-TCP) with SeNPs, is developed to prepare an injectable, anti-collapse, shape-adaptive and adhesive bone graft substitute material (PDT-TCP-SE). The PDT-TCP-SE bone graft substitute exhibits sufficient adhesion in biological microenvironments and osteoinductive activity, angiogenic effect and anti-inflammatory as well as anti-oxidative effect in vitro and in vivo. Moreover, the PDT-TCP-SE can protect BMSCs from erastin-induced ferroptosis through the Sirt1/Nrf2/GPX4 antioxidant pathway, which, in together, demonstrated the bone graft substitute material as an emerging biomaterial with potential clinical application for the future treatment of osteoporotic bone defect. Statement of significanceInjectable, anti-collapse, adhesive, plastic and bioactive bone graft substitute was successfully synthesized. Incorporation of SeNPs with PDT into β-TCP regenerated new bone in-situ by moderating oxidative stress in osteoporotic bone defects area. The PDT-TCP-SE bone graft substitute reduced high ROS levels in osteoporotic bone defect microenvironment. The bone graft substitute could also moderate oxidative stress and inhibit ferroptosis via Sirt1/Nrf2/GPX4 pathway in vitro. Moreover, the PDT-TCP-SE bone graft substitute could alleviate the inflammatory environment and promote bone regeneration in osteoporotic bone defect in vivo. This biomaterial has the advantages of simple synthesis, biocompatibility, anti-collapse, injectable, and regulation of oxidative stress level, which has potential application value in bone tissue engineering.

Citric Acid Cross-Linked Gelatin-Based Composites with Improved Microhardness.

The aim of this study is to investigate the influence of cross-linking and reinforcements in gelatin on the physico-mechanical properties of obtained composites. The gelatin-based composites cross-linked with citric acid (CA) were prepared: gelatin type B (GB) and β-tricalcium phosphate (β-TCP) and novel hybrid composite GB with β-TCP and hydroxyapatite (HAp) particles, and their structure, thermal, and mechanical properties were compared with pure gelatin B samples. FTIR analysis revealed that no chemical interaction between the reinforcements and gelatin matrix was established during the processing of hybrid composites by the solution casting method, proving the particles had no influence on GB cross-linking. The morphological investigation of hybrid composites revealed that cross-linking with CA improved the dispersion of particles, which further led to an increase in mechanical performance. The microindentation test showed that the hardness value was increased by up to 449%, which shows the high potential of β-TCP and HAp particle reinforcement combined with CA as a cross-linking agent. Furthermore, the reduced modulus of elasticity was increased by up to 288%. Results of the MTT assay on L929 cells have revealed that the hybrid composite GB-TCP-HA-CA was not cytotoxic. These results showed that GB cross-linked with CA and reinforced with different calcium phosphates presents a valuable novel material with potential applications in dentistry.

Favorable osteogenic activity of vericiguat doped in β-tricalcium phosphate: In vitro and in vivo studies.

Recently, more and more studies have shown that guanylate cyclase, an enzyme that synthesizes cyclic guanosine monophosphate (cGMP), plays an important role in bone metabolism. Vericiguat (VIT), a novel oral soluble guanylate cyclase stimulator, directly generates cyclic guanosine monophosphate and reduce the death incidence from cardio-vascular causes or hospitalization. Recent studies have shown beneficial effects of VIT in animal models of osteoporosis, but very little is currently known about the effects of VIT on bone defects in the osteoporotic states. Therefore, in this study, β-tricalcium phosphate (β-TCP) was used as a carrier to explore the effect of local VIT administration on the repair of femoral metaphyseal bone defects in ovariectomized (OVX) rats. When MC3T3-E1 was cultured in the presence of H2H2, VIT, similar to Melatonin (MT), therapy could increase the matrix mineralization and ALP, SOD2, SIRT1, and OPG expression, reduce ROS and Mito SOX production, RANKL expression, Promote the recovery of mitochondrial membrane potential. In the OVX rat model, VIT increases the osteogenic effect of β-TCP and better results were obtained at a dose of 5mg. Local use of VIT can inhibit increased OC, BMP2 and RUNX2 expressions in bone tissue, while decreased SOST and TRAP expressions by RT-PCR and immunohistochemistry. Thereby, VIT stimulates bone regeneration and is a promising candidate for promoting bone repair in osteoporosis.