[Surgical Stabilization of Traumatic Multiple Rib Fractures Using Absorbable Osteosynthesis Agent(u-HA/PLLA Composite Material)].

In case that met several indication criteria with 4 or more rib fractures, we performed surgical stabilization of multiple fractured ribs using a plate and screw system( Super FIXORB MX) that was made of uncalcined hydroxyapatite (u-HA)/poly-L-lactic acid (PLLA) composite material with excellent bioactivity and absorbability. We report our clinical experience of 7 cases in which this device was used. Although there is still room for further consideration of the technique and the strength of the device itself, computed tomography( CT) images taken 9 months after surgery showed that the fixative device was almost assimilated with the bone at the fracture repair site in cases where fixation was successful.

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.

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.

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.

Do Implant Coatings Affect Healing of Placed Implants? An Umbrella Review.

PURPOSE: To analyze the available evidence and assess the effect of different implant coatings on healing outcomes. MATERIALS AND METHODS: Using the PICOS strategy, a structured question was formed. A protocol was agreed upon and registered with PROSPERO (no. CRD42022321926). The MEDLINE, Embase, Cochrane Database of Systematic Reviews, Scopus, Web of Science, Pubmed, and ScienceDirect databases were searched using a structured strategy. Study selection was independently carried out in duplicate, first by title and abstract, then by full-text assessment. Quality and risk of bias were independently assessed in duplicate using AMSTAR 2 and ROBIS. Data extraction was independently undertaken in duplicate using a predefined extraction form. RESULTS: The search yielded 11 systematic reviews for inclusion. The most commonly assessed coatings were based on calcium phosphate-including hydroxyapatite (HA), brushite, and bioabsorbable nano-HA-followed by bisphosphonate, then bioactive glass coatings. Included reviews most frequently assessed marginal bone loss (MBL), bone-to-implant contact (BIC), and survival/success rates. There was considerable heterogeneity and small sample sizes. The quality assessment suggested low confidence in the reviews and high risk of bias. CONCLUSIONS: The included reviews provide weak evidence that implant coatings improve osseointegration and reduce MBL following implant placement. There was weak evidence for progressive complications for calcium phosphate coatings. Further research and long-term multicenter controlled clinical trials with improved standardization and control of bias are required to better understand the effects of coating implants.

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.

Penicillium oxalicum induced phosphate precipitation enhanced cadmium (Cd) immobilization by simultaneously accelerating Cd biosorption and biomineralization.

Soil cadmium (Cd) is immobilized by the progressing biomineralization process as microbial induced phosphate precipitation (MIPP), which is regulated by phosphate (P) solubilizing microorganisms and P sources. However, little attention has been paid to the implications of Cd biosorption during MIPP. In this study, the newly isolated Penicillium oxalicum could immobilize 5.4-12.6 % of Cd2+, while the presence of hydroxyapatite (HAP) considerably enhanced Cd2+ immobilization in P. oxalicum and reached over 99 % Cd2+ immobilization efficiency within 7 days. Compared to P. oxalicum mono inoculation, MIPP dramatically boosted Cd biosorption and biomineralization efficiency by 71 % and 16 % after 96 h cultivation, respectively. P. oxalicum preferred to absorbing Cd2+ and reaching maximum Cd2+ biosorption efficiency of 87.8 % in the presence of HAP. More surface groups in P. oxalicum and HAP mineral involved adsorption which resulted in the formation of Cd-apatite [Ca8Cd2(PO4)6(OH)2] via ion exchange. Intracellular S2-, secreted organic acids and soluble P via HAP solubilization complexed with Cd2+, progressively mineralized into Cd5(PO4)3OH, Cd(H2PO4)2, C4H6CdO4 and CdS. These results suggested that Cd2+ immobilization was enhanced simultaneously by the accelerated biosorption and biomineralization during P. oxalicum induced P precipitation. Our findings revealed new mechanisms of Cd immobilization in MIPP process and offered clues for remediation practices at metal contaminated sites.

Enhanced multi-metals stabilization: Synergistic insights from hydroxyapatite and peroxide dosing strategies.

Sediment contamination by heavy metals is a pressing environmental concern. While in situ metal stabilization techniques have shown promise, a great challenge remains in the simultaneous immobilization of multi-metals co-existing in contaminated sediments. This study aims to address this challenge by developing a practical method for stabilizing multi-metals by hydroxyapatite and calcium peroxide (HAP/CaO2) dosing strategies. Results showed that dosing 15.12 g of HAP/CaO2 at a ratio of 3:1 effectively transformed labile metals into stable fractions, reaching reaction kinetic equilibrium within one month with a pseudo-second-order kinetic (R2 > 0.98). The stable fractions of Nickel (Ni), Chromium (Cr), and lead (Pb) increased by approximately 16.9 %, 26.7 %, and 21.9 %, respectively, reducing heavy metal mobility and ensuring leachable concentrations complied with the stringent environmental Class I standard. Mechanistic analysis indicated that HAP played a crucial role in Pb stabilization, exhibiting a high rate of 0.0176 d-1, while Cr and Ni stabilization primarily occurred through the formation of hydroxide precipitates, as well as the slowly elevated pH (>8.5). Importantly, the proposed strategy poses a minimal environmental risk to benthic organisms exhibits almost negligible toxicity towards Vibrio fischeri and the Chironomus riparius, and saves about 71 % of costs compared to kaolinite. These advantages suggest the feasibility of HAP/CaO2 dosing strategies in multi-metal stabilization in contaminated sediments.

Deterioration phenomenon of Pb-contaminated aqueous solution remediation and enhancement mechanism of nano-hydroxyapatite-assisted biomineralization.

Modern metallurgical and smelting activities discharge the lead-containing wastewater, causing serious threats to human health. Bacteria and urease applied to microbial-induced carbonate precipitation (MICP) and enzyme-induced carbonate precipitation (EICP) are denatured under high Pb2+ concentration. The nano-hydroxyapatite (nHAP)-assisted biomineralization technology was applied in this study for Pb immobilization. Results showed that the extracellular polymers and cell membranes failed to secure the urease activity when subjected to 60 mM Pb2+. The immobilization efficiency dropped to below 50% under MICP, whereas it due to a lack of extracellular polymers and cell membranes dropped to below 30% under EICP. nHAP prevented the attachment of Pb2+ either through competing with bacteria and urease or promoting Ca2+/Pb2+ ion exchange. Furthermore, CO32- from ureolysis replaced the hydroxyl (-OH) in hydroxylpyromorphite to encourage the formation of carbonate-bearing hydroxylpyromorphite of higher stability (Pb10(PO4)6CO3). Moreover, nHAP application overcame an inability to provide nucleation sites by urease. As a result, the immobilization efficiency, when subjected to 60 mM Pb2+, elevated to above 80% under MICP-nHAP and to some 70% under EICP-nHAP. The findings highlight the potential of applying the nHAP-assisted biomineralization technology to Pb-containing water bodies remediation.

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.

Reparative osteogenesis in mandible in cases of filling a bone defect with hydroxyapatite-containing osteotropic material and injecting the surrounding soft tissues with thymalin: experimental and morphological study.

OBJECTIVE: Aim of the study was to identify the morphological features of reparative osteogenesis in the lower jaw bone of rats in cases of filling a bone defect with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT") and injecting the surrounding soft tissues with thymalin. PATIENTS AND METHODS: Materials and Methods: An experiment was conducted on 48 mature rats of the WAG population weighing 160-180 grams which were divided into four groups. 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. Histological, morphometric and statistical research methods were used. RESULTS: Results: In this study, it was shown by the authors an activation of reparative osteogenesis in the lower jaw under conditions of simultaneous filling the bone defect with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT") and injection the surrounding bone defect soft tissue with thymalin. Stimulation of reparative osteogenesis in the lower jaw of rats occurred due to rapid cleaning of the bone defect cavity from necrotic tissues and hematoma fragments; a decrease in the number of neutrophil leukocytes, an increase in the number and morphofunctional state of monocytes, macrophages, lymphocytes, cells of fibroblastic differon; balanced change (increase or decrease) in the number and morphofunctional state of bone forming osteoblasts and bone resorbing osteoclasts depending on the stage of reparative osteogenesis; activation of hematopoietic processes in lamellar bone tissue from the regenerate; activation of bone tissue mineralization processes. CONCLUSION: Conclusions: Thymalin injection in the soft tissues surrounding the bone defect in the lower jaw, filled with hydroxyapatite-containing osteotropic material (bone graft "Biomin GT"), significantly stimulates the process of reparative osteogenesis, which makes it possible to recommend this technique in dentistry for treatment the patients with mandible bone tissue defects.

Zinc-doped hydroxyapatite as a pH responsive drug delivery system for anticancer drug 6-mercaptopurine.

6-Mercaptopurine (6MP) is commonly used in the treatment of acute lymphoblastic leukemia as an important agent in maintenance therapy. Despite its therapeutic benefits, 6MP has some limitations during therapy. Taking into account the disadvantages during 6MP therapy, there is a great need to create an appropriate delivery system for this drug. 6MP contains in its structure nitrogen and sulfur atoms capable of forming coordination compounds with metal ions, for example zinc. Therefore, in this work, we prepared biocompatible hydroxyapatite (HAp) doped with zinc ions, and used it as a carrier for 6MP. Doped HAp has not been used as a carrier for this drug before. The work proved that the prepared carrier-drug system has a particle size of about 130 nm, which indicates its potential for intravenous delivery. In addition, in an acidic environment (imitating cancer cells), the carrier agglomerates allow targeted release of the drug. The drug is evenly distributed, which indicates that the doses released from it will always be comparable. The release of the drug in a neutral environment is long-lasting in controlled doses, whereas in an acidic environment it is immediate. The obtained results indicate the high potential of the material in both slow-release and cancer-targeted release of 6MP.

3D-printed PCL framework assembling ECM-inspired multi-layer mineralized GO-Col-HAp microscaffold for in situ mandibular bone regeneration.

BACKGROUND: In recent years, natural bone extracellular matrix (ECM)-inspired materials have found widespread application as scaffolds for bone tissue engineering. However, the challenge of creating scaffolds that mimic natural bone ECM's mechanical strength and hierarchical nano-micro-macro structures remains. The purposes of this study were to introduce an innovative bone ECM-inspired scaffold that integrates a 3D-printed framework with hydroxyapatite (HAp) mineralized graphene oxide-collagen (GO-Col) microscaffolds and find its application in the repair of mandibular bone defects. METHODS: Initially, a 3D-printed polycaprolactone (PCL) scaffold was designed with cubic disks and square pores to mimic the macrostructure of bone ECM. Subsequently, we developed multi-layer mineralized GO-Col-HAp microscaffolds (MLM GCH) to simulate natural bone ECM's nano- and microstructural features. Systematic in vitro and in vivo experiments were introduced to evaluate the ECM-inspired structure of the scaffold and to explore its effect on cell proliferation and its ability to repair rat bone defects. RESULTS: The resultant MLM GCH/PCL composite scaffolds exhibited robust mechanical strength and ample assembly space. Moreover, the ECM-inspired MLM GCH microscaffolds displayed favorable attributes such as water absorption and retention and demonstrated promising cell adsorption, proliferation, and osteogenic differentiation in vitro. The MLM GCH/PCL composite scaffolds exhibited successful bone regeneration within mandibular bone defects in vivo. CONCLUSIONS: This study presents a well-conceived strategy for fabricating ECM-inspired scaffolds by integrating 3D-printed PCL frameworks with multilayer mineralized porous microscaffolds, enhancing cell proliferation, osteogenic differentiation, and bone regeneration. This construction approach holds the potential for extension to various other biomaterial types.

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.

Systemically administered zoledronic acid activates locally implanted synthetic hydroxyapatite particles enhancing peri-implant bone formation: A regenerative medicine approach to improve fracture fixation.

Fracture fixation in an ageing population is challenging and fixation failure increases mortality and societal costs. We report a novel fracture fixation treatment by applying a hydroxyapatite (HA) based biomaterial at the bone-implant interface and biologically activating the biomaterial by systemic administration of a bisphosphonate (zoledronic acid, ZA). We first used an animal model of implant integration and applied a calcium sulphate (CaS)/HA biomaterial around a metallic screw in the tibia of osteoporotic rats. Using systemic ZA administration at 2-weeks post-surgery, we demonstrated that the implant surrounded by HA particles showed significantly higher peri­implant bone formation compared to the unaugmented implants at 6-weeks. We then evaluated the optimal timing (day 1, 3, 7 and 14) of ZA administration to achieve a robust effect on peri­implant bone formation. Using fluorescent ZA, we demonstrated that the uptake of ZA in the CaS/HA material was the highest at 3- and 7-days post-implantation and the uptake kinetics had a profound effect on the eventual peri­implant bone formation. We furthered our concept in a feasibility study on trochanteric fracture patients randomized to either CaS/HA augmentation or no augmentation followed by systemic ZA treatment. Radiographically, the CaS/HA group showed signs of increased peri­implant bone formation compared with the controls. Finally, apart from HA, we demonstrated that the concept of biologically activating a ceramic material by ZA could also be applied to ß-tricalcium phosphate. This novel approach for fracture treatment that enhances immediate and long-term fracture fixation in osteoporotic bone could potentially reduce reoperations, morbidity and mortality. STATEMENT OF SIGNIFICANCE: • Fracture fixation in an ageing population is challenging. Biomaterial-based augmentation of fracture fixation devices has been attempted but lack of satisfactory biological response limits their widespread use. • We report the biological activation of locally implanted microparticulate hydroxyapatite (HA) particles placed around an implant by systemic administration of the bisphosphonate zoledronic acid (ZA). The biological activation of HA by ZA enhances peri­implant bone formation. •Timing of ZA administration after HA implantation is critical for optimal ZA uptake and consequently determines the extent of peri­implant bone formation. • We translate the developed concept from small animal models of implant integration to a proof-of-concept clinical study on osteoporotic trochanteric fracture patients. • ZA based biological activation can also be applied to other calcium phosphate biomaterials.

Mechanoregulation analysis of bone formation in tissue engineered constructs requires a volumetric method using time-lapsed micro-computed tomography.

Bone can adapt its microstructure to mechanical loads through mechanoregulation of the (re)modeling process. This process has been investigated in vivo using time-lapsed micro-computed tomography (micro-CT) and micro-finite element (FE) analysis using surface-based methods, which are highly influenced by surface curvature. Consequently, when trying to investigate mechanoregulation in tissue engineered bone constructs, their concave surfaces make the detection of mechanoregulation impossible when using surface-based methods. In this study, we aimed at developing and applying a volumetric method to non-invasively quantify mechanoregulation of bone formation in tissue engineered bone constructs using micro-CT images and FE analysis. We first investigated hydroxyapatite scaffolds seeded with human mesenchymal stem cells that were incubated over 8 weeks with one mechanically loaded and one control group. Higher mechanoregulation of bone formation was measured in loaded samples with an area under the curve for the receiver operating curve (AUCformation) of 0.633-0.637 compared to non-loaded controls (AUCformation: 0.592-0.604) during culture in osteogenic medium (p < 0.05). Furthermore, we applied the method to an in vivo mouse study investigating the effect of loading frequencies on bone adaptation. The volumetric method detected differences in mechanoregulation of bone formation between loading conditions (p < 0.05). Mechanoregulation in bone formation was more pronounced (AUCformation: 0.609-0.642) compared to the surface-based method (AUCformation: 0.565-0.569, p < 0.05). Our results show that mechanoregulation of formation in bone tissue engineered constructs takes place and its extent can be quantified with a volumetric mechanoregulation method using time-lapsed micro-CT and FE analysis. STATEMENT OF SIGNIFICANCE: Many efforts have been directed towards optimizing bone scaffolds for tissue growth. However, the impact of the scaffolds mechanical environment on bone growth is still poorly understood, requiring accurate assessment of its mechanoregulation. Existing surface-based methods were unable to detect mechanoregulation in tissue engineered constructs, due to predominantly concave surfaces in scaffolds. We present a volumetric approach to enable the precise and non-invasive quantification and analysis of mechanoregulation in bone tissue engineered constructs by leveraging time-lapsed micro-CT imaging, image registration, and finite element analysis. The implications of this research extend to diverse experimental setups, encompassing culture conditions, and material optimization, and investigations into bone diseases, enabling a significant stride towards comprehensive advancements in bone tissue engineering and regenerative medicine.

Pirarucu hydroxyapatite applied to ternary competitive adsorption of synthetic basic dyes as contaminants of emerging concern: kinetic, equilibrium, and ANN studies.

This study investigated the single and multicomponent adsorption of three emerging pollutants, the basic dyes Rhodamine 6G (R6G), Auramine-O (AO), and Brilliant Green (BG) by using hydroxyapatite synthesized from Pirarucu scales as adsorbent (HAP). The adsorption process was studied using seven different systems: AO-single, R6G-single, BG-single, R6G + AO, BG + AO, BG + R6G, and R6G + AO + BG. For kinetics, the initial concentration of each adsorbate per system was 50 mg/L, the results showed that the singular adsorption of these dyes was best-represented by the pseudo-second-order model (qAO = 62.54 mg/g, qR6G = 7.91 mg/g, qBG = 62.40 mg/g), however, the multicomponent adsorption was well-fitted by a pseudo-first-order model (ternary system: qAO = 56.21 mg/g, qR6G = 14.95 mg/g, qBG = 60.62 mg/g). For equilibrium, the initial concentration of each adsorbate per system was 10-300 mg/L, and the single adsorption systems were best represented by the Langmuir model. Nonetheless, the results displayed in the multicomponent mixture showed the presence of inflection points of AO and R6G whenever BG was present in solution with C0 > 150 mg/L, thus indicating that BG has greater affinity with HAP. The presence of inflection points in the curves represented a limitation for applying traditional equilibrium models, thus, an artificial neural network (ANN) was applied to non-linear curve fit this process and satisfactorily predicted the kinetics and equilibrium data. Finally, the analysis of thermodynamics for the ternary mixture revealed that the adsorption process is spontaneous (ΔG < 0), endothermic (ΔH > 0), and increases to a disorganized state as the temperature rises (ΔS > 0).

Development and application of hydroxyapatite-based scaffolds for bone tissue regeneration: A systematic literature review.

Hydroxyapatite [HA, Ca10(PO4)6(OH)2], with its robust biocompatibility and bioactivity, has found extensive utility in bone grafting, replacement therapies, and supplemental medical materials. HA is highly regarded for its osteoconductive properties because it boasts hydrophilicity, nontoxicity, non-allergenicity, and non-mutagenicity. Nevertheless, HA's intrinsic mechanical weakness has spurred efforts to enhance its properties. This enhancement is achieved through ion incorporation, with elements such as magnesium, zinc, lithium, strontium, boron, and others being integrated into the HA structure. In the domain of orthopedics, HA-based scaffolds have emerged as a solution for addressing prevalent issues like bone deformities and defects stemming from congenital anomalies, injuries, trauma, infections, or tumors. The fabrication of three-dimensional scaffolds (3D scaffolds) has enabled advancements in bone regeneration and replacement, with a focus on practical applications such as repairing calvarial, skull, and femoral defects. In vitro and in vivo assessments have substantiated the effectiveness of 3D scaffolds for bone defect repair, regeneration, and tissue engineering. Beyond bone-related applications, scaffolds demonstrate versatility in enhancing cartilage healing and serving as bioimplants. The wide array of scaffold applications underscores their ongoing potential for further development in the realm of medical science.

Doxorubicin loaded cerium substituted hydroxyapatite nanoparticles: A promising new therapeutic approach for bone regeneration, doxorubicin delivery, and cancer treatment.

The current study used the precipitation method to prepare pure calcium hydroxyapatite (HA) and cerium-substituted hydroxyapatite (Ce-HA) nanoparticles, where cerium ions were exchanged into the HA structure at different concentrations ranging from 3 to 7 wt%. X-ray powder diffraction (XRD), field emission scanning electron microscopy (FE-SEM), high resolution transmission electron microscopy (HR-TEM), Fourier transform infrared (FTIR) spectroscopy, Brunauer-Emmett-Teller (BET) surface area measurements, and zeta potential were used to examine the structural characteristics of the nanoparticles. Additionally, the antibacterial and antifungal effects of the produced materials on Gram-positive, Gram-negative, and fungal bacterial species were studied. Nanoparticles with cerium doping showed effective antibacterial and antifungal properties. All samples were tested for bioactivity in simulated body fluid (SBF), and the formation of an apatite layer on their surfaces was highlighted using SEM in conjunction with energy-dispersive X-rays (EDX).Doxorubicin (DOX) release from Ce-HA nanoparticles and pure HA was tested in phosphate-buffered saline (PBS) for up to 28 days. Both nanoparticles were able to release the drug while still being semi-fully loaded. Similarly, the cytotoxic effect of all produced samples on the MG-63 cell line was evaluated, and all samples showed good cytocompatibility. The cytotoxic effect of doxorubicin-loaded nanoparticles showed promising anticancer activity against bone cancer cells, especially samples with high cerium content. The resulting nanoparticles show excellent promising ability for the delivery of doxorubicin to bone cancer with the capacity for bone regeneration.

Fabrication of Novel 3-D Nanocomposites of HAp-TiC-h-BN-ZrO2: Enhanced Mechanical Performances and In Vivo Toxicity Study for Biomedical Applications.

Due to excellent biocompatibility, bioactivities, and osteoconductivity, hydroxyapatite (HAp) is considered as one of the most suitable biomaterials for numerous biomedical applications. Herein, HAp was fabricated using a bottom-up approach, i.e., a wet chemical method, and its composites with TiC, h-BN, and ZrO2 were fabricated by a solid-state reaction method with enhanced mechanical and biological performances. Structural, surface morphology, and mechanical behavior of the fabricated composites were characterized using various characterization techniques. Furthermore, transmission electron microscopy study revealed a randomly oriented rod-like morphology, with the length and width of these nanorods ranging from 78 to 122 and from 9 to 13 nm. Moreover, the mechanical characterizations of the composite HZBT4 (80HAp-10TiC-5h-BN-5ZrO2) reveal a very high compressive strength (246 MPa), which is comparable to that of the steel (250 MPa), fracture toughness (14.78 MPa m1/2), and Young's modulus (1.02 GPa). In order to check the biocompatibility of the composites, numerous biological tests were also performed on different body organs of healthy adult Sprague-Dawley rats. This study suggests that the composite HZBT4 could not reveal any significant influence on the hematological, serum biochemical, and histopathological parameters. Hence, the fabricated composite can be used for several biological applications, such as bone implants, bone grafting, and bone regeneration.