Preparation of mesoporous silica/hydroxyapatite loaded quercetin nanoparticles and research on its antibacterial properties.

In this study, amino-functionalized mesoporous silica/hydroxyapatite nanoparticles (MSNS/HAP) with the property of acid dissociation have been prepared as a traditional Chinese medicine monomer carriers to improve the drug loading rate and antibacterial properties of antimicrobial quercetin (QUE) in vitro. The experimental results confirm that the drug loading rate of MSNs/HAP is 28.94 %, which is about 3.6 times higher than that of aminated mesoporous sililca nanoparticles (MSNs). The drug release of QUE on MSNs/HAP is pH-sensitive in phosphate buffered saline (pH=4.0-7.4). The above fabricated traditional Chinese medicine monomer modified nanocomposites (QUE@MSNs/HAP) displays concentration-dependent inhibitory effect, which shows better antibacterial effect than free QUE. The minimum inhibitory concentration for two tested bacteria, Staphylococcus aureus (S.aureus) and Escherichia coli (E.coli), is 256 mg·L -1. In summary, QUE@MSNs/HAP have successfully prepared, which not only improves the bio-availability of QUE, but also has acid-sensitive drug release properties. Compared with free QUE, its antibacterial performance significantly enhances, which provides a theoretical basis for the application of Chinese medicine molecules in bacterial treatment.

Expression features of T-lymphocytes, B-lymphocytes and macrophages in the post-traumatic regenerate of the mandible rats under conditions of filling a bone defect with hydroxyapatite-containing osteotropic material and thymalin injecting the surrounding soft tissues.

OBJECTIVE: Aim: The purpose of the study was to determine the features of the expression of T-lymphocytes, B-lymphocytes, macrophages in the post-traumatic regenerate of the mandible rats under conditions of filling a bone defect with hydroxyapatite-containing osteotropic material and thymalin injecting the surrounding soft tissues. PATIENTS AND METHODS: Materials and Methods: An experiment was conducted on 48 mature rats of the WAG population weighing 160-180 grams. Four groups were formed. Group 1 included 12 rats with a simulated holey defect in the lower jaw. Group 2 included 12 rats with a simulated holey defect in the lower jaw followed by its closure with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT"). Group 3 included 12 rats with a simulated holey defect in the lower jaw with injecting the surrounding soft tissues with thymalin. Group 4 included 12 rats with a simulated holey defect in the lower jaw followed by its closure with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT") and injecting the surrounding soft tissues with thymalin. The material for the morphological study was a fragment of the lower jaw from the area of the simulated holey defect. An immunohistochemical study was aperformed using monoclonal antibodies to CD68, CD20, CD163, CD86, CD3. RESULTS: Results: A comprehensive experimental and morphological study conducted by the authors revealed that thymalin injection of the soft tissues surrounding the bone defect of the lower jaw, filled with hydroxyapatite-containing osteotropic material "Biomin GT", stimulates local immune reactions in the post-traumatic regenerate, which is manifested, firstly, by an increase in the number T-lymphocytes on the 3rd day of the experiment and their increase up to the 28th day; secondly, by increasing the number of B-lymphocytes on the 14th day of the experiment with their further increase up to the 28th day; thirdly, by increasing the number of macrophages on the 3rd day of the experiment and their growth up to the 28th day; fourth, changes in macrophages phenotypes (decrease in the number of M1-macrophages and increase in the number of M2-macrophages). CONCLUSION: Conclusions: Stimulation of local immune reactions in the post-traumatic regenerate can be one of the mechanisms that activate reparative osteogenesis in the lower jaw of rats under the conditions of filling bone defects with hydroxyapatite-containing osteotropic material "Biomin GT" and thymalin injecting the surrounding soft tissues.

Redefined ion association constants have consequences for calcium phosphate nucleation and biomineralization.

Calcium orthophosphates (CaPs), as hydroxyapatite (HAP) in bones and teeth are the most important biomineral for humankind. While clusters in CaP nucleation have long been known, their speciation and mechanistic pathways to HAP remain debated. Evidently, mineral nucleation begins with two ions interacting in solution, fundamentally underlying solute clustering. Here, we explore CaP ion association using potentiometric methods and computer simulations. Our results agree with literature association constants for Ca2+ and H2PO4-, and Ca2+ and HPO42-, but not for Ca2+ and PO43- ions, which previously has been strongly overestimated by two orders of magnitude. Our data suggests that the discrepancy is due to a subtle, premature phase separation that can occur at low ion activity products, especially at higher pH. We provide an important revision of long used literature constants, where association of Ca2+ and PO43- actually becomes negligible below pH 9.0, in contrast to previous values. Instead, [CaHPO4]0 dominates the aqueous CaP speciation between pH ~6-10. Consequently, calcium hydrogen phosphate association is critical in cluster-based precipitation in the near-neutral pH regime, e.g., in biomineralization. The revised thermodynamics reveal significant and thus far unexplored multi-anion association in computer simulations, constituting a kinetic trap that further complicates aqueous calcium phosphate speciation.

Inhibiting Pathological Calcium Phosphate Mineralization: Implications for Disease Progression.

Pathological calcifications, especially calcium phosphate microcalcifications (MCs), appear in most early breast cancer lesions, and their formation correlates with more aggressive tumors and a poorer prognosis. Hydroxyapatite (HA) is a key MC component that crystallizes in the tumor microenvironment. It is often associated with malignant breast cancer lesions and can trigger tumorigenesis in vitro. Here, we investigate the impact of additives on HA crystallization and inhibition, and how precancerous breast cells respond to minerals that are deposited in the presence of these additives. We show that nonstoichiometric HA spontaneously crystallizes in a solution simulating the tumor microenvironmental fluids and exhibits lump-like morphology similar to breast cancer MCs. In this system, the effectiveness of poly(aspartic acid) and poly(acrylic acid) (PAA) to inhibit HA is examined as a potential route to improve cancer prognosis. In the presence of additives, the formation of HA lumps is associated with the promotion or only minimal inhibition of mineralization, whereas the formation of amorphous calcium phosphate (ACP) lumps is followed by inhibition of mineralization. PAA emerges as a robust HA inhibitor by forming spherical ACP particles. When precancerous breast cells are exposed to various HA and ACP minerals, the most influential factors on cell proliferation are the mineral phase and whether the mineral is in the form of discrete particles or particle aggregates. The tumorigenic effects on cells, ranging from cytotoxicity and suppression of proliferation to triggering of proliferation, can be summarized as HA particles < HA aggregates < ACP particles < ACP aggregates. The cellular response to minerals can be attributed to a combination of factors, including mineral phase, crystallinity, morphology, surface texture, aggregation state, and surface potential. These findings have implications for understanding mineral-cell interactions within the tumor microenvironment and suggest that, in some cases, the byproducts of HA inhibition can contribute to disease progression more than HA itself.

Melt Electrowriting Combined with Fused Deposition Modeling Printing for the Fabrication of Three-Dimensional Biomimetic Scaffolds for Osteotendinous Junction Regeneration.

Purpose: This study aims to explore a novel scaffold for osteotendinous junction regeneration and to preliminarily verify its osteogenic and tenogenic abilities in vitro. Methods: A polycaprolactone (PCL) scaffold with aligned and orthogonal fibers was created using melt electrowriting (MEW) and fused deposition modeling (FDM). The scaffold was coated with Type I collagen, and hydroxyapatite was carefully added to separate the regions intended for bone and tendon regeneration, before being rolled into a cylindrical shape. Human adipose-derived stem cells (hADSCs) were seeded to evaluate viability and differentiation. Scaffold characterization was performed with Scanning Electron Microscope (SEM). Osteogenesis was assessed by alkaline phosphatase (ALP) and Alizarin red staining, while immunostaining and transcription-quantitative polymerase chain reaction (RT-qPCR) evaluated osteogenic and tendogenic markers. Results: Scaffolds were developed in four variations: aligned (A), collagen-coated aligned (A+C), orthogonal (O), and mineral-coated orthogonal (O+M). SEM analysis confirmed surface morphology and energy-dispersive X-ray spectroscopy (EDS) verified mineral coating on O+M types. Hydrophilicity and mechanical properties were optimized in modified scaffolds, with A+C showing increased tensile strength and O+M improved in compression. hADSCs demonstrated good viability and morphology across scaffolds, withO+M scaffolds showing higher cell proliferation and osteogenic potential, and A and A+C scaffolds supporting tenogenic differentiation. Conclusion: This study confirms the potential of a novel PCL scaffold with distinct regions for osteogenic and tenogenic differentiation, supporting the regeneration of osteotendinous junctions in vitro.

Enhancing Bone Implants: Magnesium-Doped Hydroxyapatite for Stronger, Bioactive, and Biocompatible Applications.

Hydroxyapatite (HAp) with the chemical formula Ca10(PO4)6(OH)2 is an inorganic material that exhibits morphology and composition similar to those of human bone tissues, making it highly desirable for bone regeneration applications. As one of the most biocompatible materials currently in use, HAp has undergone numerous attempts to enhance its mechanical strength. This research focuses on investigating the influence of magnesium (Mg) incorporation on the structural and mechanical properties of synthesized magnesium-doped hydroxyapatite (MgHAp) samples. Apart from its biocompatibility, Mg possesses a density and elasticity comparable to those of human bone. Therefore, incorporating Mg into HAp can be pivotal for improving bone formation. Previous studies have not extensively explored the structural changes induced by Mg substitution in HAp, which motivated us to revisit this issue. Hydrothermal synthesis technique was used to synthesize MgHAp samples with varying molar concentrations (x = 0, 0.5, 1.0, and 1.5). Theoretical simulation of HAp and MgHAp for obtaining 3D structures has been done, and theoretical X-ray diffraction (XRD) data have been compared with the experimental XRD data. Rietveld analysis revealed the alteration and deviation of lattice parameters with an increase in the Mg content, which ultimately affect the structure as well the mechanical properties of prepared samples. The findings revealed an increase in compressive stress and fracture toughness as the Mg concentration in the composition increased. Furthermore, using a finite-element analysis technique and modeling of the mechanical testing data, the von Mises stress distribution and Young's modulus values were calculated, demonstrating the similarity of the prepared samples to human cortical bone. Biocompatibility assessments using NIH-3T3 fibroblast cells confirmed the biocompatible and bioactive nature of the synthesized samples. MgHAp exhibits great potential for biomedical applications in the dental, orthopedic, and tissue engineering research fields.

Bioactive Moldable Click Chemistry Polymer Cement with Nano-Hydroxyapatite and Growth Factor-Enhanced Posterolateral Spinal Fusion in a Rabbit Model.

Spinal injuries or diseases necessitate effective fusion solutions, and common clinical approaches involve autografts, allografts, and various bone matrix products, each with limitations. To address these challenges, we developed an innovative moldable click chemistry polymer cement that can be shaped by hand and self-cross-linked in situ for spinal fusion. This self-cross-linking cement, enabled by the bioorthogonal click reaction, excludes the need for toxic initiators or external energy sources. The bioactivity of the cement was promoted by incorporating nanohydroxyapatite and microspheres loaded with recombinant human bone morphogenetic protein-2 and vascular endothelial growth factor, fostering vascular induction and osteointegration. The release kinetics of growth factors, mechanical properties of the cement, and the ability of the scaffold to support in vitro cell proliferation and differentiation were evaluated. In a rabbit posterolateral spinal fusion model, the moldable cement exhibited remarkable induction of bone regeneration and effective bridging of spine vertebral bodies. This bioactive moldable click polymer cement therefore presents a promising biomaterial for spinal fusion augmentation, offering advantages in safety, ease of application, and enhanced bone regrowth.

Steric and energetic studies on the influence of cellulose on the adsorption effectiveness of Mg trapped hydroxyapatite for enhanced remediation of chlorpyrifos and omethoate pesticides.

Magnesium-trapped hydroxyapatite (Mg.HP) was hybridized with cellulose fiber to produce a bio-composite (CLF/HP) with enhanced adsorption affinities for two types of toxic pesticides (chlorpyrifos (CF) and omethoate (OM)). The enhancement influence of the hybridized cellulose on the adsorption performances of Mg.HP was illustrated based on the determined steric and energetic factors. The computed CF and OM adsorption performances of CLF/HP during the saturation phases are 279.8 mg/g and 317.9 mg/g, respectively, which are significantly higher than the determined values using Mg/HP (143.4 mg/g (CF) and 145.3 mg/g (OM)). The steric analysis demonstrates a strong impact of the hybridization process on the reactivity of the surface of the composite. While CLF/HP reflects effective uptake site densities (Nm) of 93.3 mg/g (CF) and 135.3 mg/g (OM), the estimated values for Mg.HP are 51.2 mg/g (CF) and 46.11 mg/g (OM), which explain the reported enhancement in the adsorption performances of the composite. The capacity of each uptake site to be occupied with more than one molecule (n (CF) = 3-3.74 and n (OM) = 2.35-3.54) suggests multimolecular uptake. The energetic factors suggested physical mechanistic processes of spontaneous and exothermic behaviors either during the uptake of CF or OM.

Electrophoretic Deposition of Calcium Phosphates on Carbon-Carbon Composite Implants: Morphology, Phase/Chemical Composition and Biological Reactions.

Despite a long period of application of metal implants, carbon-carbon medical composites are also widely used for bone defect prosthesis in surgery, dentistry, and oncology. Such implants might demonstrate excellent mechanical properties, but their biocompatibility and integration efficiency into the host should be improved. As a method of enhancing, the electrophoretic deposition of fine-dispersed hydroxyapatite (HAp) on porous carbon substrates might be recommended. With electron microscopy, energy dispersion X-ray and Raman spectroscopy, and X-ray diffraction, we found that the deposition and subsequent heat post-treatment (up to the temperature of 400 °C for 1 h) did not lead to any significant phase and chemical transformations of raw non-stoichometric HAp. The Ca/P ratio was ≈1.51 in the coatings. Their non-toxicity, cyto- and biocompatibility were confirmed by in vitro and in vivo studies and no adverse reactions and side effects had been detected in the test. The proposed coating and subsequent heat treatment procedures provided improved biological responses in terms of resorption and biocompatibility had been confirmed by histological, magnetic resonance and X-ray tomographic ex vivo studies on the resected implant-containing biopsy samples from the BDF1 mouse model. The obtained results are expected to be useful for modern medical material science and clinical applications.

In vivo research on 3D-printed composite PLGA and PDLLA-HA absorbable scaffolds for repairing radius defects in rabbits.

OBJECTIVES: Despite being an important research topic in oral biomaterials, few studies have demonstrated the differences between poly(d,l-lactide-co-glycolide)/hydroxyapatite (PLGA/HA) and poly(d,l-lactic acid)/hydroxyapatite (PDLLA/HA). In this study, PLGA/HA and PDLLA/HA scaffolds were prepared using three-dimensional (3D) printing technology and implanted into radius defects in rabbits to assess their effects on bone regeneration. METHODS: In this study, 6 mm × 4 mm bone defects were generated in the bilateral radii of rabbits. 3D-printed PLGA/HA and PDLLA/HA scaffolds were implanted into the defects. X-ray imaging, micro-computed tomography, and hematoxylin-eosin staining were performed to observe the degradation of the materials, the presence of new bone, and bone remodeling in the bone defect area. RESULTS: The PLGA/HA scaffolds displayed complete degradation at 20 weeks, whereas PDLLA/HA scaffolds exhibited incomplete degradation. Active osteoblasts were detected in both groups. The formation of new bone, bone marrow cavity reconstruction, and cortical bone remodeling were better in the PLGA/HA group than in the PDLLA/HA group. CONCLUSIONS: PLGA/HA scaffolds performed better than PDLLA/HA scaffolds in repairing bone defects, making the former scaffolds more suitable as bone substitutes at the same high molecular weight.

Synthesis of pure and doped nano-calcium phosphates using different conventional methods for biomedical applications: a review.

The applications of calcium phosphates (hydroxyapatite, tetracalcium phosphate, tricalcium phosphate (alpha and beta), fluorapatite, di-calcium phosphate anhydrous, and amorphous calcium-phosphate) are increasing day by day. Calcium hydroxyapatite, commonly known as hydroxyapatite (HAp), represents a mineral form of calcium apatite. Owing to its close molecular resemblance to the mineral constituents of bones, teeth, and hard tissues, HAp is often employed in the biomedical domain. In addition, it is extensively employed in various sectors such as the remediation of water, air, and soil pollution. The key advantage of HAp lies in its potential to accommodate a wide variety of anionic and cationic substitutions. Nevertheless, HAp and tricalcium phosphate (TCP) syntheses typically involve the use of chemical precursors containing calcium and phosphorus sources and employ diverse techniques, such as solid-state, wet, and thermal methods or a combination of these processes. Researchers are increasingly favoring natural sources such as bio-waste (eggshells, oyster shells, animal bones, fish scales, etc.) as viable options for synthesizing HAp. Interestingly, the synthesis route significantly influences the morphology, size, and crystalline phase of calcium phosphates. In this review paper, we highlight both dry and wet methods, which include six commonly used synthesis methods (i.e. solid-state, mechano-chemical, wet-chemical precipitation, hydrolysis, sol-gel, and hydrothermal methods) coupled with the variation in source materials and their influence in modifying the structural morphology from a bulky state to nanoscale to explore the applications of multifunctional calcium phosphates in different formats.

An innovative 3D hydroxyapatite patient-specific implant for maxillofacial bone reconstruction: A case series of 13 patients.

The study aimed to evaluate and discuss the use of an innovative PSI made of porous hydroxyapatite, with interconnected porosity promoting osteointegration, called MyBone Custom® implant (MBCI), for maxillofacial bone reconstruction. A multicentric cohort of 13 patients underwent maxillofacial bone reconstruction surgery using MBCIs for various applications, from genioplasty to orbital floor reconstruction, including zygomatic and mandibular bone reconstruction, both for segmental defects and bone augmentation. The mean follow-up period was 9 months (1-22 months). No infections, displacements, or postoperative fractures were reported. Perioperative modifications of the MBCIs were possible when necessary. Additionally, surgeons reported significant time saved during surgery. For patients with postoperative CT scans, osteointegration signs were visible at the 6-month postoperative follow-up control, and continuous osteointegration was observed after 1 year. The advantages and disadvantages compared with current techniques used are discussed. MBCIs offer new bone reconstruction possibilities with long-term perspectives, while precluding the drawbacks of titanium and PEEK. The low level of postoperative complications associated with the high osteointegration potential of MBCIs paves the way to more extensive use of this new hydroxyapatite PSI in maxillofacial bone reconstruction.

Preparation of an injectable and photocurable carboxymethyl cellulose/hydroxyapatite composite and its application in cranial regeneration.

Limited bone regeneration, uncontrollable degradation rate, mismatched defect zone and poor operability have plagued the reconstruction of irregular bone defect by tissue-engineered materials. A combination of biomimetic scaffolds with hydroxyapatite has gained great popularity in promoting bone regeneration. Therefore, we designed an injectable, photocurable and in-situ curing hydrogel by methacrylic anhydride -modified carboxymethyl cellulose (CMC-MA) loading with spherical hydroxyapatite (HA) to highly simulate the natural bony matrix and match any shape of damaged tissue. The prepared carboxymethyl cellulose-methacrylate/ hydroxyapatite(CMC-MA/HA) composite presented good rheological behavior, swelling ratio and mechanical property under light illumination. Meanwhile, this composite hydrogel promoted effectively proliferation, supported adhesion and upregulated the osteogenic-related genes expression of MC3T3-E1 cells in vitro, as well as the activity of the osteogenic critical protein, Integrin α1, ß1, Myosin 9, Myosin 10, BMP-2 and Smad 1 in Integrin/BMP-2 signal pathway. Together, the composite hydrogels realized promotion of bone regeneration, deformity improvement, and the enhanced new bone strength in skull defect. It also displayed a good histocompatibility and stability of subcutaneous implantation in vivo. Overall, this study laid the groundwork for future research into developing a novel biomaterial and a minimally invasive therapeutic strategies for reconstructing bone defects and contour deficiencies.

Magnetic Hydroxyapatite Nanoparticles in Regenerative Medicine and Nanomedicine.

This review focuses on the latest advancements in magnetic hydroxyapatite (mHA) nanoparticles and their potential applications in nanomedicine and regenerative medicine. mHA nanoparticles have gained significant interest over the last few years for their great potential, offering advanced multi-therapeutic strategies because of their biocompatibility, bioactivity, and unique physicochemical features, enabling on-demand activation and control. The most relevant synthetic methods to obtain magnetic apatite-based materials, either in the form of iron-doped HA nanoparticles showing intrinsic magnetic properties or composite/hybrid compounds between HA and superparamagnetic metal oxide nanoparticles, are described as highlighting structure-property correlations. Following this, this review discusses the application of various magnetic hydroxyapatite nanomaterials in bone regeneration and nanomedicine. Finally, novel perspectives are investigated with respect to the ability of mHA nanoparticles to improve nanocarriers with homogeneous structures to promote multifunctional biological applications, such as cell stimulation and instruction, antimicrobial activity, and drug release with on-demand triggering.

Evaluation of in vitro corrosion behavior and biocompatibility of poly[xylitol-(1,12-dodecanedioate)](PXDD)-HA coated porous iron for bone scaffolds applications.

The present study evaluates the corrosion behavior of poly[xylitol-(1,12-dodecanedioate)](PXDD)-HA coated porous iron (PXDD140/HA-Fe) and its cell-material interaction aimed for temporary bone scaffold applications. The physicochemical analyses show that the addition of 20 wt.% HA into the PXDD polymers leads to a higher crystallinity and lower surface roughness. The corrosion assessments of the PXDD140/HA-Fe evaluated by electrochemical methods and surface chemistry analysis indicate that HA decelerates Fe corrosion due to a lower hydrolysis rate following lower PXDD content and being more crystalline. The cell viability and cell death mode evaluations of the PXDD140/HA-Fe exhibit favorable biocompatibility as compared to bare Fe and PXDD-Fe scaffolds owing to HA's bioactive properties. Thus, the PXDD140/HA-Fe scaffolds possess the potential to be used as a biodegradable bone implant.

Lysophosphatidic Acid/Polydopamine-Modified nHA Composite Scaffolds for Enhanced Osteogenesis via Upregulating the Wnt/Beta-Catenin Pathway.

Guided bone regeneration (GBR) technology has been widely used for the regeneration of periodontal bone defects. However, the limited mechanical properties and bone regeneration potential of the currently available GBR membranes often limit their repair effectiveness. In this paper, serum-derived growth factor lysophosphatidic acid (LPA) nanoparticles and dopamine-decorative nanohydroxyapatite (pDA/nHA) particles were double-loaded into polylactic-glycolic acid/polycaprolactone (PLGA/PCL) scaffolds as an organic/inorganic biphase delivery system, namely, PP-pDA/nHA-LPA scaffolds. Physicochemical properties and osteogenic ability in vitro and in vivo were performed. Scanning electron microscopy and mechanical tests showed that the PP-pDA/nHA-LPA scaffolds had a 3D bionic scaffold structure with improved mechanical properties. In vitro cell experiments demonstrated that the PP-pDA/nHA-LPA scaffolds could significantly enhance the attachment, proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. In vivo, the PP-pDA/nHA-LPA scaffolds exhibited great cytocompatibility and cell recruitment ability in 2- and 4-week subcutaneous implantation experiments and significantly promoted bone regeneration in the periodontal defect scaffold implantation experiment. Moreover, LPA-loaded scaffolds were confirmed to enhance osteogenic activities by upregulating the expression of ß-catenin and further activating the Wnt/ß-catenin pathway. These results demonstrate that the biphase PP-pDA/nHA-LPA delivery system is a promising material for the GBR.

Degradable Nanohydroxyapatite-Reinforced Superglue for Rapid Bone Fixation and Promoted Osteogenesis.

Bone glue with robust adhesion is crucial for treating complicated bone fractures, but it remains a formidable challenge to develop a "true" bone glue with high adhesion strength, degradability, bioactivity, and satisfactory operation time in clinical scenarios. Herein, inspired by the hydroxyapatite and collagen matrix composition of natural bone, we constructed a nanohydroxyapatite (nHAP) reinforced osteogenic backbone-degradable superglue (O-BDSG) by in situ radical ring-opening polymerization. nHAP significantly enhances adhesive cohesion by synergistically acting as noncovalent connectors between polymer chains and increasing the molecular weight of the polymer matrix. Moreover, nHAP endows the glue with bioactivity to promote osteogenesis. The as-prepared glue presented a 9.79 MPa flexural adhesion strength for bone, 4.7 times that without nHAP, and significantly surpassed commercial cyanoacrylate (0.64 MPa). O-BDSG exhibited degradability with 51% mass loss after 6 months of implantation. In vivo critical defect and tibia fracture models demonstrated the promoted osteogenesis of the O-BDSG, with a regenerated bone volume of 75% and mechanical function restoration to 94% of the native tibia after 8 weeks. The glue can be flexibly adapted to clinical scenarios with a curing time window of about 3 min. This work shows promising prospects for clinical application in orthopedic surgery and may inspire the design and development of bone adhesives.

Cross Talk Between Cells and the Current Bioceramics in Bone Regeneration: A Comprehensive Review.

The conventional approach for addressing bone defects and stubborn non-unions typically involves the use of autogenous bone grafts. Nevertheless, obtaining these grafts can be challenging, and the procedure can lead to significant morbidity. Three primary treatment strategies for managing bone defects and non-unions prove resistant to conventional treatments: synthetic bone graft substitutes (BGS), a combination of BGS with bioactive molecules, and the use of BGS in conjunction with stem cells. In the realm of synthetic BGS, a multitude of biomaterials have emerged for creating scaffolds in bone tissue engineering (TE). These materials encompass biometals like titanium, iron, magnesium, and zinc, as well as bioceramics such as hydroxyapatite (HA) and tricalcium phosphate (TCP). Bone TE scaffolds serve as temporary implants, fostering tissue ingrowth and the regeneration of new bone. They are meticulously designed to enhance bone healing by optimizing geometric, mechanical, and biological properties. These scaffolds undergo continual remodeling facilitated by bone cells like osteoblasts and osteoclasts. Through various signaling pathways, stem cells and bone cells work together to regulate bone regeneration when a portion of bone is damaged or deformed. By targeting signaling pathways, bone TE can improve bone defects through effective therapies. This review provided insights into the interplay between cells and the current state of bioceramics in the context of bone regeneration.

[A polylactic acid/hydroxyapatite/scholzite composite scaffold for promoting healing of osteoporotic bone defects in rats].

OBJECTIVE: To investigate the release kinetics of Zn2+ from nZCP-loaded polylactic acid/hydroxyapatite (PLA/HA) composite scaffold (PHZ) and determine the optimal nZCP content in the scaffold. METHODS: The particle size of nZCP was measured by DLS measurement, and PXRD, FTIR, and SEM were used to characterize the scaffolds and nZCP distribution; EDS was used to analyze element composition of the scaffold. Compression strength of the scaffold was determined, and ion release profile was investigated using ICP-MS. The biocompatibility of the materials was evaluated by CCK-8 assay and dead/alive staining of rat bone marrow stem cells (BMSCs) incubated with their aqueous extracts. ALP staining, alizarin red staining, RT-qPCR, and Western blotting were used to assess the osteogenic potential of the treated cells. In a rat model of bilateral ovariectomy (OVX) with femoral condylar bone defect, PHZ-1, PHZ-2, PHZ-3 or PLA/HA scaffold was implanted into the bone defect, and bone repair was observed using a microCT scanner and histological staining at 6 and 12 weeks. RESULTS: DLS, PXRD, SEM, FTIR, and EDS confirmed successful synthesis of 10-nm ZCP and efficient nZCP loading in the scaffold. PHZ-2 and PHZ-3 had significantly greater compression strength than PLA/HA. ICP-MS showed that Zn2+ release from PHZ-1, PHZ-2 and PHZ-3 were all optimal for promoting osteogenesis. In rat BMSCs, all the 4 scaffolds showed good biocompatibility, and their extracts enhanced ALP activity and extracellular matrix mineralization and promoted expressions of ALP, RUNX2, and OCN in the cells. In the rat models, nZCP in the implants improved bone graft integration at 6 weeks, and PHZ-2 and PHZ-3 more effectively induced new bone formation at 12 weeks (P < 0.05). CONCLUSION: PHZ scaffold is capable of stable Zn2+ release to promote osteoporotic bone defect healing, and PHZ-2 and PHZ-3 scaffolds with nZCP mass fraction of 4.5%-7.5% have better osteogenic activity.

Pore graded borosilicate bioactive glass scaffolds: in vitro dissolution and cytocompatibility.

3D borosilicate bioactive glass (1393B20 and B12.5MgSr) scaffolds were prepared by robocasting, with and without a dense layer at the top. Pore graded scaffolds are promising as they allow for membrane deposition and could limit the risk of soft tissue infiltration. In vitro dissolution was studied in tris(hydroxymethyl)aminomethane (TRIS) and Simulated Body Fluid (SBF). 1393B20 scaffolds dissolved faster than B12.5MgSr in TRIS whereas they dissolved slower in SBF. The difference in dissolution profiles, as a function of the medium used, is assigned to the different rates of precipitation of hydroxyapatite (HA). While the precipitation of calcium phosphate (CaP) in the form of HA, first sign of bioactivity, was confirmed by ICP, FTIR-ATR and SEM-EDX analysis for both compositions, 1393B20 was found to precipitate HA at a faster rate. The presence of a dense top layer did not significantly impact the dissolution rate and CaP precipitation. In vitro cell culture was performed using human adipose-derived stem cells (hADSCs). Prior to cell plating, a preincubation of 3 days was found optimum to prevent burst ion release. In direct contact, cells proliferate and spread on the scaffolds while maintaining characteristic spindle morphology. Cell plated on 1393B20 scaffolds showed increased viability when compared to cell plated on B12.5MgSr. The lower cell viability, when testing B12.5MgSr, was assigned to the depletion of Ca2+ ions from culture medium and higher pH. Static cell culture leads to believe that the scaffold produced from the 1393B20 glass composition are promising in bone regeneration applications.