Fluorinated hydroxyapatite conditions a favorable osteo-immune microenvironment via triggering metabolic shift from glycolysis to oxidative phosphorylation.

BACKGROUND: Biological-derived hydroxyapatite is widely used as a bone substitute for addressing bone defects, but its limited osteoconductive properties necessitate further improvement. The osteo-immunomodulatory properties hold crucial promise in maintaining bone homeostasis, and precise modulation of macrophage polarization is essential in this process. Metabolism serves as a guiding force for immunity, and fluoride modification represents a promising strategy for modulating the osteoimmunological environment by regulating immunometabolism. In this context, we synthesized fluorinated porcine hydroxyapatite (FPHA), and has demonstrated its enhanced biological properties and osteogenic capacity. However, it remains unknown whether and how FPHA affects the immune microenvironment of the bone defects. METHODS: FPHA was synthesized and its composition and structural properties were confirmed. Macrophages were cultured with FPHA extract to investigate the effects of FPHA on their polarization and the related osteo-immune microenvironment. Furthermore, total RNA of these macrophages was extracted, and RNA-seq analysis was performed to explore the underlying mechanisms associated with the observed changes in macrophages. The metabolic states were evaluated with a Seahorse analyzer. Additionally, immunohistochemical staining was performed to evaluate the macrophages response after implantation of the novel bone substitutes in critical size calvarial defects in SD rats. RESULTS: The incorporation of fluoride ions in FPHA was validated. FPHA promoted macrophage proliferation and enhanced the expression of M2 markers while suppressing the expression of M1 markers. Additionally, FPHA inhibited the expression of inflammatory factors and upregulated the expression of osteogenic factors, thereby enhancing the osteogenic differentiation capacity of the rBMSCs. RNA-seq analysis suggested that the polarization-regulating function of FPHA may be related to changes in cellular metabolism. Further experiments confirmed that FPHA enhanced mitochondrial function and promoted the metabolic shift of macrophages from glycolysis to oxidative phosphorylation. Moreover, in vivo experiments validated the above results in the calvarial defect model in SD rats. CONCLUSION: In summary, our study reveals that FPHA induces a metabolic shift in macrophages from glycolysis to oxidative phosphorylation. This shift leads to an increased tendency toward M2 polarization in macrophages, consequently creating a favorable osteo-immune microenvironment. These findings provide valuable insights into the impact of incorporating an appropriate concentration of fluoride on immunometabolism and macrophage mitochondrial function, which have important implications for the development of fluoride-modified immunometabolism-based bone regenerative biomaterials and the clinical application of FPHA or other fluoride-containing materials.

Reconstruction of Segmental Bone Defect in Canine Tibia Model Utilizing Bi-Phasic Scaffold: Pilot Study.

The reunion and restoration of large segmental bone defects pose significant clinical challenges. Conventional strategies primarily involve the combination of bone scaffolds with seeded cells and/or growth factors to regulate osteogenesis and angiogenesis. However, these therapies face inherent issues related to immunogenicity, tumorigenesis, bioactivity, and off-the-shelf transplantation. The biogenic micro-environment created by implanted bone grafts plays a crucial role in initiating the bone regeneration cascade. To address this, a highly porous bi-phasic ceramic synthetic bone graft, composed of hydroxyapatite (HA) and alumina (Al), was developed. This graft was employed to repair critical segmental defects, involving the creation of a 2 cm segmental defect in a canine tibia. The assessment of bone regeneration within the synthetic bone graft post-healing was conducted using scintigraphy, micro-CT, histology, and dynamic histomorphometry. The technique yielded pore sizes in the range of 230-430 µm as primary pores, 40-70 µm as secondary inner microchannels, and 200-400 nm as tertiary submicron surface holes. These three components are designed to mimic trabecular bone networks and to provide body fluid adsorption, diffusion, a nutritional supply, communication around the cells, and cell anchorage. The overall porosity was measured at 82.61 ± 1.28%. Both micro-CT imaging and histological analysis provided substantial evidence of robust bone formation and the successful reunion of the critical defect. Furthermore, an histology revealed the presence of vascularization within the newly formed bone area, clearly demonstrating trabecular and cortical bone formation at the 8-week mark post-implantation.

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.

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.

[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.

Reconstructing Critical-Sized Mandibular Defects in a Rabbit Model: Enhancing Angiogenesis and Facilitating Bone Regeneration via a Cell-Loaded 3D-Printed Hydrogel-Ceramic Scaffold Application.

In this study, we propose a spatially patterned 3D-printed nanohydroxyapatite (nHA)/beta-tricalcium phosphate (ß-TCP)/collagen composite scaffold incorporating human dental pulp-derived mesenchymal stem cells (hDP-MSCs) for bone regeneration in critical-sized defects. We investigated angiogenesis and osteogenesis in a rabbit critical-sized mandibular defect model treated with this engineered construct. The critical and synergistic role of collagen coating and incorporation of stem cells in the regeneration process was confirmed by including a cell-free uncoated 3D-printed nHA/ß-TCP scaffold, a stem cell-loaded 3D-printed nHA/ß-TCP scaffold, and a cell-free collagen-coated 3D-printed nHA/ß-TCP scaffold in the experimental design, in addition to an empty defect. Posteuthanasia evaluations through X-ray analysis, histological assessments, immunohistochemistry staining, histomorphometry, and reverse transcription-polymerase chain reaction (RT-PCR) suggest the formation of substantial woven and lamellar bone in the cell-loaded collagen-coated 3D-printed nHA/ß-TCP scaffolds. Histomorphometric analysis demonstrated a significant increase in osteoblasts, osteocytes, osteoclasts, bone area, and vascularization compared to that observed in the control group. Conversely, a significant decrease in fibroblasts/fibrocytes and connective tissue was observed in this group compared to that in the control group. RT-PCR indicated a significant upregulation in the expression of osteogenesis-related genes, including BMP2, ALPL, SOX9, Runx2, and SPP1. The findings suggest that the hDP-MSC-loaded 3D-printed nHA/ß-TCP/collagen composite scaffold is promising for bone regeneration in critical-sized defects.

Unprecedented Approach of Fabrication and Analysis of a Bioactive PDMS/Hydroxyapatite/Graphene Nanocomposite Scaffold with a Vascular Channel to Combat Carcinogenesis.

In the present investigation, natural bone-derived hydroxyapatite (HA, 2 wt %) and/or exfoliated graphene (Gr, 0.1 wt %)-embedded polydimethylsiloxane (PDMS) elastomeric films were prepared using a vascular method. The morphology, mechanical properties, crystallinity, and chemical structure of the composite films were evaluated. The in vitro biodegradation kinetics of the films indicates their adequate physiological stability. Most of the results favored PDMS/HA/Gr as a best composite scaffold having more than 703% elongation. A simulation study of the microfluidic vascular channel of the PDMS/HA/Gr scaffold suggests that the pressure drop at the outlet became greater (from 1.19 to 0.067 Pa) unlike velocity output (from 0.071 to 0.089 m/s), suggesting a turbulence-free laminar flow. Our bioactive scaffold material, PDMS/HA/Gr, showed highest cytotoxicity toward the lung cancer and breast cancer cells through Runx3 protein-mediated cytotoxic T lymphocyte (CTL) generation. Our data and predicted mechanism also suggested that the PDMS/HA/Gr-supported peripheral blood mononuclear cells (PBMCs) not only increased the generation of CTL but also upregulated the expression of RUNX3. Since the PDMS/HA/Gr scaffold-supported Runx3 induced CTL generation caused maximum cell cytotoxicity of breast cancer (MCF-7) and lung cancer (A549) cells, PDMS/HA/Gr can be treated as an excellent potential candidate for CTL-mediated cancer therapy.

Excellent survival of two anatomically adapted hydroxyapatite coated cementless Total Hip Arthroplasties. A mean follow-up of 11.3 years.

There are many different types of cementless anatomically adapted Total Hip Arthroplasties (THAs) on the market, the Anatomic Benoist Gerard (ABG) I and II are such types of cementless THAs. In this retrospective single-centre study we evaluated the overall survival with revision for any reason and aseptic loosening as endpoint at more than 11 years follow-up. Between 2000 and 2004, 244 cementless THAs were performed in 230 patients in a primary care hospital. At a mean of 11.3 years follow-up (range 9.8 - 12.8 years) clinical examination, plain radiography and Patient Reported Outcome Measures (PROMs) were obtained and analysed. The PROMs consisted of the Oxford Hip Score (OHS) and the Western Ontario and McMaster University Index (WOMAC). At a mean of 11.3 years follow-up 32 patients (13.1%) had died of unrelated causes. Of the remaining cohort all 198 patients (212 THAs) have been reached for evaluation. There were no patients considered as lost to follow-up. At a mean of 11.3 years 11 patients (11 THAs) have had a revision of either the femoral implant or acetabular component resulting in an overall survival of 95.5%. There was no statistically significant difference (p=0.564) in survival between the ABG I and II THAs. Radiographic there were no changes between the ABG I and II last follow up. The ABG II performed statistically significant better in PROMs. We concluded that both anatomically adapted hydroxyapatite coated cementless THAs show excellent survival at more than 11 years follow-up.

Challenging applicability of ISO 10993-5 for calcium phosphate biomaterials evaluation: Towards more accurate in vitro cytotoxicity assessment.

Research on biomaterials typically starts with cytocompatibility evaluation, using the ISO 10993-5 standard as a reference that relies on extract tests to determine whether the material is safe (cell metabolic activity should exceed 70 %). However, the generalized approach within the standard may not accurately reflect the material's behavior in direct contact with cells, raising concerns about its effectiveness. Calcium phosphates (CaPs) are a group of materials that, despite being highly biocompatible and promoting bone formation, still exhibit inconsistencies in basic cytotoxicity evaluations. Hence, in order to test the cytocompatibility dependence on different experimental setups and material-cell interactions, we used amorphous calcium phosphate, α-tricalcium phosphate, hydroxyapatite, and octacalcium phosphate (0.1 mg/mL to 5 mg/mL) with core cell lines of bone microenvironment: mesenchymal stem cells, osteoblast-like and endothelial cells. All materials have been characterized for their physicochemical properties before and after cellular contact and once in vitro assays were finalized, groups identified as 'cytotoxic' were further analyzed using a modified Annexin V apoptosis assay to accurately determine cell death. The obtained results showed that indirect contact following ISO standards had no sensitivity of tested cells to the materials, but direct contact tests at physiological concentrations revealed decreased metabolic activity and viability. In summary, our findings offer valuable guidelines for handling biomaterials, especially in powder form, to better evaluate their biological properties and avoid false negatives commonly associated with the traditional standard approach.

Synthesis and Evaluation of Radiogallium Labeled Bone-Imaging Probes Using Oligo-γ-Carboxy Glutamic Acid Peptides as Carriers to Bone.

We investigated the importance of the carboxy group density in bone affinity during the development of peptide-based bone-seeking radiopharmaceuticals and carriers. Oligo-γ-carboxy glutamic acid peptides [(Gla)n] with higher carboxy group density than oligo-glutamic acid peptides [(Glu)n] and oligo-aspartic acid peptides [(Asp)n] were chosen. Using the radiogallium chelator N,N'-bis-[2-hydroxy-5-(carboxyethyl)benzyl]ethylenediamine-N,N'-diacetic acid (HBED-CC), we synthesized [67Ga]Ga-HBED-CC-(Gla)n (n = 1, 2, 5, 8, 11, or 14) with high yields. Hydroxyapatite-binding assays, biodistribution, and SPECT imaging showed higher affinity and bone accumulation for [67Ga]Ga-HBED-CC-(Gla)n compared to [67Ga]Ga-HBED-CC-(Glu)n. Notably, [67Ga]Ga-HBED-CC-(Gla)8 and [67Ga]Ga-HBED-CC-(Gla)11 exhibited superior bone accumulation and rapid blood clearance. SPECT/CT imaging with [67Ga]Ga-HBED-CC-(Gla)8 exclusively visualized the bone tissue. These findings support the potential use of [67Ga]Ga-HBED-CC-(Gla)n as excellent bone-imaging PET probes, suggesting (Gla)n peptides are superior bone-seeking carriers.

Study on the performance and mechanism of cobaltous ion removal from water by a high-efficiency strontium-doped hydroxyapatite adsorbent.

In this study, a high-efficiency strontium-doped hydroxyapatite (Sr-HAP) adsorbent was synthesized by a sol-gel method for removing cobaltous ions (Co(II)) from water. The effects of adsorbent dose, initial solution pH, initial Co(II) concentration and temperature on the removal performance of Co(II) were investigated. Experimental results indicated that the optimum Sr-HAP dose was 0.30 g/50 mL solution, the Sr-HAP adsorbent could effectively remove Co(II) in a wide pH range of 3-8. Increasing temperature was conducive to the adsorption, and the maximum Co(II) adsorption capacity by Sr-HAP reached 48.467 mg/g at 45 °C. The adsorption of Co(II) followed the pseudo-second-order kinetic model, indicating that the Co(II) adsorption by Sr-HAP was attributed mainly to chemisorption. The isothermal adsorption results showed that at lower Co(II) equilibrium concentration, the Langmuir model fitted the data better than the Freundlich model but opposite at higher Co(II) equilibrium concentration. Therefore, the adsorption of Co(II) was a process from monolayer adsorption to multilayer adsorption with the increase of the Co(II) equilibrium concentration. The diffusion analysis of Co(II) to Sr-HAP indicated that the internal diffusion and surface adsorption were the rate-controlled steps of Co(II) adsorption. Thermodynamic study demonstrated that the Co(II) adsorption process was spontaneous and endothermic. The mechanism study revealed that in addition to chemisorption, Sr-HAP also removed Co(II) ions from water via ion exchange and surface complexation.

3D printing of customized bioceramics for promoting bone tissue regeneration by regulating sympathetic nerve behavior.

Numerous studies have shown that there are multiple neural activities involved in the process of bone resorption and bone regeneration, and promoting osteogenesis by promoting neural network reconstruction is an effective strategy for repairing critical size bone defects. However, traumatic bone defects often cause activation of the sympathetic nervous system (SNS) in the damaged area, releasing excess catecholamines (CAs), resulting in a decrease in the rate of bone formation. Herein, a 3D-printed scaffold loaded with propranolol (PRN) is proposed to reduce CA concentrations in bone defect areas and promote bone regeneration through drug release. For this purpose, PRN-loaded methacrylated gelatin (GelMA) microspheres were mixed with low-concentration GelMA and perfused into a 3D-printed porous hydroxyapatite (HAp) scaffold. By releasing PRN, which can block ß-adrenergic receptors, it hinders the activation of sympathetic nerves and inhibits the release of excess CA by the SNS. At the same time, the composite scaffold recruits bone marrow mesenchymal stem cells (BMSCs) and promotes the differentiation of BMSCs in the direction of osteoblasts, which effectively promotes bone regeneration in the rabbit femoral condyle defect model. The results of the study showed that the release of PRN from the composite scaffold could effectively hinder the activation of sympathetic nerves and promote bone regeneration, providing a new strategy for the treatment of bone defects.

The interplay between crystallinity and the levels of Zn and carbonate in synthetic microcalcifications directs thyroid cell malignancy.

One of the key challenges in diagnosing thyroid cancer lies in the substantial percentage of indeterminate diagnoses of thyroid nodules that have undergone ultrasound-guided fine-needle aspiration (FNA) biopsy for cytological evaluation. This delays the definitive diagnosis and treatment plans. We recently demonstrated that hydroxyapatite microcalcifications (MCs) aspirated from thyroid nodules may aid nodule diagnosis based on their composition. In particular, Zn-enriched MCs have emerged as potential cancer biomarkers. However, a pertinent question remains: is the elevated Zn content within MCs a consequence of cancer, or do the Zn-enriched MCs encourage tumorigenesis? To address this, we treated the human thyroid cancer cell line MDA-T32 with synthetic MC analogs comprising hydroxyapatite crystals with varied pathologically relevant Zn fractions and assessed the cellular response. The MC analogs exhibited an irregular surface morphology similar to FNA MCs observed in cancerous thyroid nodules. These MC analogs displayed an inverse relationship between Zn fraction and crystallinity, as shown by X-ray diffractometry. The zeta potential of the non-Zn-bearing hydroxyapatite crystals was negative, which decreased once Zn was incorporated into the crystal. The MC analogs were not cytotoxic. The cellular response to exposure to these crystals was evaluated in terms of cell migration, proliferation, the tendency of the cells to form multicellular spheroids, and the expression of cancer markers. Our findings suggest that, if thyroid MCs play a role in promoting cancerous behavior in vivo, it is likely a result of the interplay of crystallinity with Zn and carbonate fractions in MCs.

Dynamic Hybrid Module-Driven NK Cell Stimulation and Release for Tumor Immunotherapy.

Natural killer (NK) cells have become a powerful candidate for adoptive tumor immunotherapy, while their therapeutic efficacy in solid tumors remains unsatisfactory. Here, we developed a hybrid module with an injectable hydrogel and hydroxyapatite (HAp) nanobelts for the controlled delivery of NK cells to enhance the therapy of solid tumors. Surface-functionalized HAp nanobelts modified with agonistic antibodies against NKG2D and 4-1BB and cytokines IL-2 and IL-21 support survival and dynamic activation. Thus, the HAp-modified chitosan (CS) thermos-sensitive hydrogel not only improved the retention of NK cells for more than 20 days in vivo but also increased NK cell function by more than one-fold. The unique architecture of this biomaterial complex protects NK cells from the hostile tumor environment and improves antitumor efficacy. The generation of a transient inflammatory niche for NK cells through a biocompatible hydrogel reservoir may be a conversion pathway to prevent cancer recurrence of resectable tumors.

The impact of hydroxyapatite crystal structures and protein interactions on bone's mechanical properties.

Hydroxyapatite (HAP) constitutes the primary mineral component of bones, and its crystal structure, along with the surface interaction with proteins, significantly influences the outstanding mechanical properties of bone. This study focuses on natural hydroxyapatite, constructing a surface model with calcium vacancy defects. Employing a representative model of aspartic acid residues, we delve into the adsorption mechanism on the crystal surface and scrutinize the adsorption forms of amino acid residues on HAP and calcium-deficient hydroxyapatite (CDHA) surfaces. The research also explores the impact of different environments on adsorption energy. Furthermore, a simplified sandwich structure of crystal-polypeptide-crystal is presented, analyzing the distribution of amino acid residue adsorption sites on the crystal surface of the polypeptide fragment. This investigation aims to elucidate how the stick-slip mechanism of polypeptide molecules on the crystal surface influences the mechanical properties of the system. By uncovering the interface mechanical behavior between HAP and osteopontin peptides, this article offers valuable theoretical insights for the construction and biomimetic design of biocomposites.

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.

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.

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.

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.

Is bone remodelling around fully hydroxyapatite-coated and tapered-wedge stems related to the stem fixation pattern?

PURPOSE: This study aimed to compare bone mineral density (BMD) changes around the femoral component after total hip arthroplasty (THA) in a fully hydroxyapatite-coated stem (CORAIL) and in a tapered-wedge stem (Taperloc complete) and identify predictors of BMD changes. METHODS: This retrospective study compared 43 hips in the CORAIL group and 40 hips in the Taperloc group. The relative changes in BMD at 2 years after THA measured using dual-energy X-ray absorptiometry and the three-dimensional quantified contact states of the stem with the femoral cortical bone were assessed. Predictors of the relative change in the BMD around the proximal part of the stem were examined using multiple regression analysis. RESULTS: The decrease in BMD in Gruen zone 7 was significantly less in the CORAIL group than in the Taperloc group (P = 0.02). In the CORAIL group, the contact area in any zone was not a significant predictor of the relative changes in BMD. The contact area between the Taperloc stem and the femoral cortical bone in zones 2 and 6 was a positive predictor of the relative changes in BMD in zones 1 (P = 0.02 and P = 0.04, respectively) and 2 (P = 0.008 and P = 0.004, respectively). CONCLUSION: The CORAIL stem suppressed the postoperative BMD loss around the stem, irrespective of the contact state. The Taperloc complete stem required contact with the proximal femoral metaphysis to suppress the postoperative BMD loss around the stem.