Synthetic Hydroxyapatite Research Articles

Evaluation of materials for developing a new individual dosemeter using electron spin resonance spectroscopy.

Alanine dosemeters are widely used as solid dosemeters; however, evaluating doses in the mGy order of radiation is difficult because of their lower sensitivity for low doses. We applied the electron spin resonance dosimetry technique to investigate whether hydroxyapatite, the main component of teeth, is a suitable material for a new dosemeter to detect radiation from mGy to Gy. Commercially available synthetic hydroxyapatite possesses the essential characteristics required for a dosemeter material and has been demonstrated to accurately measure doses in the mGy to Gy range.

Adsorption and dersorption of lead using synthetic hydroxyapatite material

The adsorption of Pb2+ ions in solution by synthetic hydroxyapatite material has been researched. Investigations were conducted into the effects of adsorption time, adsorbent mass, solution pH, and Pb2+ ion concentration. The material's adsorption efficiency to Pb2+ can reach 98.7%. Two adsorption isotherm models, Freunlich and Langmuir, were used to evaluate adsorption isotherms. The pseudo-first-order and pseudo-second-order adsorption kinetic models were used to assess the adsorption process's kinetics. Using the electrolysis approach, Pb2+ ions were successfully desorbed from the adsorbed HAp material while recovering metallic Pb on the cathode surface. Pb recovery efficiency can be as high as 93.84%. After desorption, the HAp material retains its original characteristics and still can adsorb Pb2+ ions with a high efficiency of 95.96%.

A novel process approach of a circular economy practice in the production of hydroxyapatite from phosphogypsum

Phosphogypsum (PG), a by-product of phosphate fertilizer industry, is chemically impure gypsum (CaSO4 · 2 H2O) containing phosphate residues. Provided by the calcium and phosphorus content, PG can be considered as a precursor for synthetic hydroxyapatite (s-HAp) production. This study proposes a two-step alkali route for s-HAp production from PG. Resulting samples were characterized by ICP-OES, SEM, XRD and FT-IR analyses in comparison with bone ash (BA) sample. Ca/P ratio (wt%) was determined as 2.46 and 2.78 for s-HAp and BA samples, respectively. SEM analysis showed the uniform distribution of spherical shaped particles in BA samples; however s-HAp particles showed irregular distribution of nearly spherical-like particles agglomerated as platelets on the surface. XRD analysis indicated that s-HAp particles possessed low crystallinity and ICDD references showed the appearance of apatite-CaOH phases. FT-IR spectrum showed the vibration bands of PO4 3− bands in the range of 1018–601 cm−1. According to characterization analyses, s-HAp samples show lower Ca/P ratio, irregular morphology, and low crystallinity due to possible impurities. Thus, further downstream operations regarding to impurity removal should be employed to develop a promising route to synthetic HAp production and employ a CE approach on industrial scale to evaluate s-HAp samples as a commercial substitute to BA.

Chondroblastoma of the femoral head-surgical management, outcomes and clinical perspectives: a case report

Chondroblastoma is a rare benign tumor predominantly affecting the epiphyses of long bones, often presenting in the second decade of life. It is known for its potential to recur and cause joint complications despite its benign histology. This report details the case of a 12-year-old boy diagnosed with chondroblastoma of the femoral head, who underwent surgical treatment involving curettage and the use of synthetic hydroxyapatite (HA) bone substitutes. The patient presented with groin pain and limping, with imaging studies revealing an osteolytic lesion in the femoral head. A core needle biopsy confirmed the diagnosis. To manage the lesion, an anterolateral approach was used to perform extensive curettage, and the defect was filled with HA blocks. Postoperatively, the patient was managed with gradual weight-bearing and regular follow-ups. At five years, the patient exhibited normal hip function with no evidence of tumor recurrence, collapse of the femoral head, or osteoarthritis. This case demonstrates that the use of synthetic HA as a bone substitute in the treatment of chondroblastoma can effectively preserve joint integrity and function, providing a viable alternative to traditional grafting methods. The approach was successful in maintaining articular congruence and preventing complications, highlighting the potential benefits of synthetic materials in managing subchondral bone lesions.

Efficient Hydroxyapatite Extraction from Salmon Bone Waste: An Improved Lab-Scaled Physico-Chemico-Biological Process.

The demand for novel tissue grafting and regenerative wound care biomaterials is growing as traditional options often fall short in biocompatibility, functional integration with human tissue, associated cost(s), and sustainability. Salmon aquaculture generates significant volumes of waste, offering a sustainable opportunity for biomaterial production, particularly in osteo-conduction/-induction, and de novo clinical/surgical bone regeneration. Henceforth, this study explores re-purposing salmon waste through a standardized pre-treatment process that minimizes the biological waste content, followed by a treatment stage to remove proteins, lipids, and other compounds, resulting in a mineral-rich substrate. Herein, we examined various methods-alkaline hydrolysis, calcination, and NaOH hydrolysis-to better identify and determine the most efficient and effective process for producing bio-functional nano-sized hydroxyapatite. Through comprehensive chemical, physical, and biological assessments, including Raman spectroscopy and X-ray diffraction, we also optimized the extraction process. Our modified and innovative alkaline hydrolysis-calcination method yielded salmon-derived hydroxyapatite with a highly crystalline structure, an optimal Ca/P ratio, and excellent biocompatibility. The attractive nano-scale cellular/tissular properties and favorable molecular characteristics, particularly well-suited for bone repair, are comparable to or even surpass those of synthetic, human, bovine, and porcine hydroxyapatite, positioning it as a promising candidate for use in tissue engineering, wound healing, and regenerative medicine indications.

Synthetic or Natural (Bio-Based) Hydroxyapatite? A Systematic Comparison between Biomimetic Nanostructured Coatings Produced by Ionized Jet Deposition.

Calcium phosphate (CaP)-based materials are largely explored in orthopedics, to increase osseointegration of the prostheses and specifically in spine surgery, to permit better fusion. To address these aims, nanostructured biogenic apatite coatings are emerging, since they better mimic the characteristics of the host tissue, thus potentially being better candidates compared to their synthetic counterpart. Here, we compare hydroxyapatite (HA) nanostructured coatings, obtained by ionized jet deposition, starting from synthetic and natural sources. The starting materials and the corresponding films are characterized and compared from a compositional and morphological point of view, then their stability is studied after post-treatment annealing. Although all the films are formed by globular aggregates and show morphological features at different scales (from nano to micro), significant differences are found in composition between the synthetic and naturally derived HA in terms of magnesium and sodium content, carbonate substitution and Ca/P ratio, while differences between the coatings obtained by the different natural HA sources are minor. In addition, the shape of the aggregates is also target-dependent. All coatings have a good stability after over 14 days of immersion in medium, with natural apatite coatings showing a better behavior, as no cracking and detachments are observed during immersion. Based on these results, both synthetic and naturally derived apatitic materials appear promising for applications in spine surgery, with coatings from natural sources possessing physiochemical properties more similar to the mineral phase of the human bone tissue.

Sinus Floor Augmentation with Synthetic Hydroxyapatite (NanoBone®) in Combination with Platelet-Rich Fibrin: A Case Series.

Several techniques have been described for maxillary sinus graft augmentation, including the lateral window technique and crestal approach with osteotomes or osseodensification. Platelet-rich fibrin has been used in maxillary sinus lift procedures due to its ability to accelerate soft and hard tissue healing. The aim of this study was to evaluate the potential of PRF in combination with the synthetic hydroxyapatite NanoBone® to enhance bone regeneration in sinus floor elevation with the lateral window technique. Out of the 50 individuals screened in a preoperative assessment visit from the CESPU-Famalicão clinical unit and intervened upon between January 2023 and December 2023, only 6 patients who met the study's inclusion criteria consented to participate. In a split-mouth study, twelve sinus graft surgeries were carried out. Our observations reveal that for the test group (NanoBone®/PRF), there is a 27.5 ± 4.9% increase new vital bone, 23.0 ± 3.7% increase in inert bone particles, and 49.4 ± 2.8% increase in connective tissue. Meanwhile, for the control group (NanoBone®), there is a 19.5 ± 3.0% increase in new vital bone, 23.4 ± 5.7% increase in inert bone particles, and 57.0 ± 3.5% increase in connective tissue. The results strongly indicate that mixing liquid PRF with NanoBone® does not have a negative influence on the amount of viable bone formation, and it seems to slightly increase the amount of new bone formation and revascularization in sinus bone graft procedures with the lateral window technique compared to the single use of NanoBone®.

Development of a composite using calcined bone powder and silane cross-linked alginate as bone substitute material.

Calcined bone is an attractive natural material for use as a bone substitute because of its cost-effectiveness and high biocompatibility, which are comparable to that of synthetic hydroxyapatite. However, the calcination process has significantly weakened the mechanical properties. In this study, a composite of calcined bovine bone powder reinforced with silane cross-linked alginate was prepared to assess its biocompatibility, osteoconductivity, and mechanical compatibility as a bone substitute material. Culture studies with osteoblast-like cells (MC3T3-E1) showed no cytotoxicity toward the composite and exhibited general cell proliferative properties in its presence. In contrast, the composite reduced the alkaline phosphatase activity of osteoblasts but led to significant noncellular apatite deposition on the surface. In addition, quasi-static compression tests of the composite revealed mechanical properties comparable to those of human cancellous bone. The mechanical properties remained stable under wet conditions and did not deteriorate significantly even after 2 weeks of immersion in simulated body fluid at 37°C. The results show that this composite, composed of calcined bone powder and silane cross-linked alginate, is a promising bone substitute material with biocompatibility, osteoconductivity, and mechanical compatibility.

3D printed hetero-layered composite scaffold with engineered superficial zone promotes osteogenic differentiation of pre-osteoblast MC3T3-E1 cells

In bone tissue engineering, a new design of composite scaffold with various compositions by incorporating both natural and synthetic cues via dual nozzle 3D printing technique could efficiently accelerate the cell differentiation to osteogenic lineage. Based on the hypothesis that a biomimetic scaffold per se can supply the vital cues to provoke bone formation, 3D printed poly(ε-caprolactone) (PCL) scaffold loaded with synthetic hydroxyapatite (HAs) decorated on graphene oxide (GO) sheets (GO@HAs), was developed. To further improve its osteogenic potential, the upper and lower layer/s of scaffolds were 3D printed using another ink containing PCL and naturally allograft HA (HAa). The FE-SEM images of the 3D printed scaffolds revealed a highly regular architecture, demonstrating the successful printability of the developed materials. The compressive mechanical test confirmed the drastic role of GO@HAs on the enhancement of Young's modulus and mechanical strength of the PCL scaffold. Moreover, existence of HAa on the upper and lower sections of scaffold interestingly improved the cellular behavior of the 3D printed scaffold without having an adverse effect on mechanical features. The experimental results indicated that such engineered scaffold significantly facilitated the cell attachment and evoked higher levels of pre-osteoblast MC3T3-E1 differentiation than PCL/GO@HAs scaffold as demonstrated by alizarin red staining, ALP activity and osteo-related gene expression. Taken together, these results indicate that such fascinating scaffold comprising both mechanical and biological cues has a high potency for inducing bone repair and also open new avenues for future advancements in the realm of bone tissue engineering exploration.

Radiological properties of nano-hydroxyapatite compared to natural equine hydroxyapatite quantified using dual-energy CT and high-field MR

In equine medicine, assisted bone regeneration, including use of biomaterial substitutes like hydroxyapatite (HAP), is crucial for addressing bone defects. To follow-up on the outcome of HAP-based bone defect treatment, the advancement in quantified diagnostic imaging protocols is needed. This study aimed to quantify and compare the radiological properties of the HAP graft and natural equine bone using Magnetic Resonance (MR) and Computed Tomography (CT), both Single (SECT) and Dual Energy (DECT). SECT and DECT, allow for the differentiation of three HAP grain sizes, by progressive increase in relative density (RD). SECT, DECT, and MR enable the differentiation between natural cortical bone and synthetic HAP graft by augmentation in Effective Z and material density (MD) in HAP/Water, Calcium/Water, and Water/Calcium reconstructions, alongside the reduction in T2 relaxation time. The proposed quantification provided valuable radiological insights into the composition of HAP grafts, which may be useful in follow-up bone defect treatment.

Effect of Physicochemical Surface Properties of Silicon-Substituted Hydroxyapatite on Angiogenesis.

Synthetic hydroxyapatite (HA) is a widely studied bioceramic for bone tissue engineering (BTE) due to its similarity to the mineral component of bone. As bone mineral contains various ionic substitutions that play a crucial role in bone metabolism, the bioactivity of HA can be improved by adding small amounts of physiologically relevant ions into its crystal structure, with silicate-substituted HA (Si-HA) showing particularly promising results. Nevertheless, it remains unclear how distinct material characteristics influence the bioactivity due to the intertwined nature of surface properties. A coculture methodology was optimized and applied for in vitro quantification of the biological response. Initially, HA and Si-HA samples were produced and characterized. To compare the bioactivity of the samples, a method was developed to measure interactions in an increasingly complex environment, first including fibronectin (FN) adsorption and subsequently cell adhesion in mono and coculture using primary human osteoblasts (hOBs) and human dermal microvascular endothelial cells (HDMECs), with and without FN precoating. An experimental set-up was designed to assess to what extent different surface features of the samples contribute to the induced biological response. An 8-nm gold sputter coating was applied to eradicate the electrochemical differences and polishing and abrading was used to reduce the differences in surface topographies. Overall, 1.25 wt% Si-HA exhibited most nanoscale variations in surface potential. In terms of bioactivity, 1.25 wt% Si-HA samples induced the highest osteoblast attachment and vessel formation. Additionally, in vitro vessel formation was established on Si-HA surfaces using a hOB:HDMEC cell ratio of 70:30 and a methodology was established that enabled the assessment of the relative effect of topographical and electrochemical features induced by silicon substitution in the HA lattice on their bioactivity. It was found that the difference in the amount of protein attached to HA and 1.25 wt% Si-HA after 2 h was affected by topographical differences. Conversely, electrochemical differences induced different vessel-like structure formation in coculture with a FN precoating. Without an FN precoating, both topographical and electrochemical differences dictated the differences in angiogenic response. Overall, 1.25 wt% Si-HA surface features appear to induce the most favorable protein adsorption and cell adhesion in mono and coculture with and without FN precoating.

A comparative study of 3D-printed scaffolds fabricated from different hydroxyapatite sources for bone tissue engineering applications

As a naturally occurring mineral component of bone, hydroxyapatite (HA) is a preferred bone-repair material in clinical medicine. This adaptable biomaterial is developed from synthetic or biological sources. The goal of this study was to investigate the physicochemical and biological properties of scaffolds made from diverse hydroxyapatite sources. We prepared hydroxyapatite powders either from naturally occurring sources, using decellularized bone extracellular matrix (DBECM) and deproteinized bovine bone (DBB), or in the laboratory using the co-precipitation method. Although XRD analysis confirmed the pure phase of HA in all three powders, XRF data found some other trace elements in bone-derived biomaterials, such as magnesium and strontium. Further, FTIR spectra showed DBECM-associated macromolecule peaks. In the second phase of this study, the particles were mixed with sodium alginate to produce bioink for 3D printing via extrusion. SEM photographs of the printed scaffolds showed a grid-like porous structure with large, interconnected pores. Although all of the scaffolds retained their structural integrity after 28 days submerged in the culture medium, DBECM-based scaffolds degraded the most. The test of Young’s modulus and compressive strength of scaffolds revealed that all scaffolds are strong enough to be employed in non-weight-bearing applications. The biological characteristics of the scaffolds were then evaluated via cytotoxicity analysis, SEM examination of cell attachment, MTT assay, ALP activity assessment, immunofluorescence staining, and Alizarin red staining. The results indicated that all three scaffolds provided a surface that promoted adhesion and proliferation of rat bone marrow mesenchymal stem cells (rMSCs), as well as stimulated the production of mineralized extracellular matrices. Additionally, our findings showed that scaffolds made from DBECM powders offer the best environment for cell activity. This is most likely due to the presence of trace elements and protein macromolecules in DBECM powders that are not found in DBB and synthetic HA. In conclusion, our comparative study revealed that while all three scaffolds are suitable for bone tissue engineering, DBECM-based scaffolds outperform DBB and synthetic HA.

Dynamics of Dental Enamel Surface Remineralization under the Action of Toothpastes with Substituted Hydroxyapatite and Birch Extract.

To address tooth enamel demineralization resulting from factors such as acid erosion, abrasion, and chronic illness treatments, it is important to develop effective daily dental care products promoting enamel preservation and surface remineralization. This study focused on formulating four toothpastes, each containing calcined synthetic hydroxyapatite (HAP) in distinct compositions, each at 4%, along with 1.3% birch extract. Substitution elements were introduced within the HAP structure to enhance enamel remineralization. The efficacy of each toothpaste formulation was evaluated for repairing enamel and for establishing the dynamic of the remineralization. This was performed by using an in vitro assessment of artificially demineralized enamel slices. The structural HAP features explored by XRD and enamel surface quality by AFM revealed notable restorative properties of these toothpastes. Topographic images and the self-assembly of HAP nanoparticles into thin films on enamel surfaces showcased the formulations' effectiveness. Surface roughness was evaluated through statistical analysis using one-way ANOVA followed by post-test Bonferroni's multiple comparison test with a p value < 0.05 significance setting. Remarkably, enamel nanostructure normalization was observed within a short 10-day period of toothpaste treatment. Optimal remineralization for all toothpastes was reached after about 30 days of treatment. These toothpastes containing birch extract also have a dual function of mineralizing enamel while simultaneously promoting enamel health and restoration.

Nanocomposite Methacrylated Silk Fibroin-Based Scaffolds for Bone Tissue Engineering.

The treatment of bone defects is a clinical challenge. Bone tissue engineering is gaining interest as an alternative to current treatments, with the development of 3D porous structures (scaffolds) helpful in promoting bone regeneration by ensuring temporary functional support. In this work, methacrylated silk fibroin (SilMA) sponges were investigated as scaffolds for bone tissue engineering by exploiting the combination of physical (induced by NaCl salt during particulate leaching) and chemical crosslinking (induced by UV-light exposure) techniques. A biomimetic approach was adopted to better simulate the extracellular matrix of the bone by introducing either natural (mussel shell-derived) or synthetic-origin hydroxyapatite nanoparticles into the SilMA sponges. The obtained materials were characterized in terms of pore size, water absorption capability and mechanical properties to understand both the effect of the inclusion of the two different types of nanoparticles and the effect of the photocrosslinking. Moreover, the SilMA sponges were tested for their bioactivity and suitability for bone tissue engineering purposes by using osteosarcoma cells, studying their metabolism by an AlamarBlue assay and their morphology by scanning electron microscopy. Results indicate that photocrosslinking helps in obtaining more regular structures with bimodal pore size distributions and in enhancing the stability of the constructs in water. Moreover, the addition of naturally derived hydroxyapatite was observed to be more effective at activating osteosarcoma cell metabolism than synthetic hydroxyapatite, showing a statistically significant difference in the AlamarBlue measurement on day 7 after seeding. The methacrylated silk fibroin/hydroxyapatite nanocomposite sponges developed in this work were found to be promising tools for targeting bone regeneration with a sustainable approach.

306 Intraoral Spectroscopy for the Identification and Study of Molar Hypomineralization

OBJECTIVES/GOALS: Molar hypomineralization (MH) is a highly prevalent dental disease that leads to rapid enamel decay even with preventative measures. While the harm is apparent, the etiology of the condition is not. Further, MH is difficult to study due to limited intact extracted teeth. Therefore, we need a method to study MH non-destructively and intraorally. METHODS/STUDY POPULATION: Recent work has shown excess proteins not commonly found in enamel are present in teeth with MH. This is theorized to be due to disruption and infiltration in the cells that form enamel leading to leftover protein and under mineralized enamel. We hypothesizethese proteins have specific spectroscopic signatures that can be detected using light. We further hypothesize that modern fiber optic probes can provide a method for non-destructive, pain-free, and rapid intraoral examination of MH. Initially, Micro Raman spectroscopy was used to detect specific vibrational bands associated with organics in teeth with MH followed by the collection of spectra of teeth with MH and heathy enamel using a spectrophotometer. These spectra were examined for any obvious differences. RESULTS/ANTICIPATED RESULTS: Currently 12 teeth were collected, and micro-computed tomography reconstructions confirmed location in 3D of MH lesions. Micro Raman of a MH-affected tooth revealed clear organic associated Amide I and III vibrational bands when compared to a synthetic hydroxyapatite (mineral in enamel) powder standard. We determined the wavelength of light that can be used to detect spectral differences between healthy enamel and teeth with MH. The next steps include optimization of the protocol of the intraoral spectrometer with the determined wavelength for implementation in clinic to allow for collection of spectra without the need for tooth extraction. DISCUSSION/SIGNIFICANCE: We hope that this work will lead to advancements in our understanding of the mechanism of MH as well as act as a proof of concept for a MH diagnostic tool. In the long term, the goal is to ideally lead to improvements in dental health care, decrease dental costs, and improve overall quality of life for the children with this condition.

Exploring the Possible Impact of Oral Nutritional Supplements on Children's Oral Health: An In Vitro Investigation.

Eight pediatric oral nutritional supplements (ONSs) and 0.5% fat bovine milk were examined in vitro regarding their effect on the adhesion of three caries-related bacteria, Streptococcus mutans (strain CCUG 11877T), Lactobacillus gasseri (strain CCUG 31451), and Scardovia wiggsiae (strain CCUG 58090), to saliva-coated hydroxyapatite, as well as their pH and capacity to withstand pH changes. Bacteria were cultivated and radiolabeled. The adhesion assays used synthetic hydroxyapatite coated with whole or parotid saliva. Measurements of pH and titration of the products with HCl and NaOH were conducted in triplicate. Three ONSs promoted the S. mutans adhesion to saliva-coated hydroxyapatite (increase from 35% to >200%), supporting caries risk enhancement. S. wigssiae and L. gasseri adhered only to one and no ONS, respectively. Most supplements had limited buffering capacity to counteract acidification changes, suggesting their low capacity to neutralize acids, and one ONS showed a significant capacity to counteract basic changes, suggesting a high erosive potential. S. mutans adhesion was influenced by the ONS pH and volume NaOH added to reach pH 10. L. gasseri and S. wiggsiae adhesion was influenced by the ONSs' carbohydrate and fat content. Interdisciplinary efforts are needed to increase awareness and prevent the possible negative impact of ONSs on children's oral health.

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 peri‑implant 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 peri‑implant 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 peri‑implant 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 peri‑implant 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 β-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 peri‑implant bone formation. •Timing of ZA administration after HA implantation is critical for optimal ZA uptake and consequently determines the extent of peri‑implant 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.

Synthesis and characterisations of clinoptilolite enriched hydroxyapatite nanoceramics by sol-gel route for bone regeneration

Hydroxyapatite (HA) has great bioactive potential in bone tissue engineering (BTE). However, the high crystalline stability of synthetic HA restricts its in-vivo bioresorbability which extends the healing time of bone defects. This study investigates doping HA with biocompatible Clinoptilolite (CLP) mineral rich in silicate and other biomimetic ions (Na+, K+, Ca+2, Mg+2 etc.). Sol-gel-based CLP doped HA nanoceramics are aimed to be exploited as bone filler substitutes with biomimetic morphology, composition, and improved biocompatibility and bioactivity. The pure and CLP (5%, 10% and 20%) doped HA ceramics were synthesised by sol-gel method to provide molecular level interactions of ions and sintered at different temperatures (800 °C, 950 °C, and 1100 °C). Morphological analyses by SEM and S-TEM showed biomimetic nano rod-like HA particles are attached to dispersed CLP sheets. Sintering of composite ceramics led to a cell-friendly interconnected porous microstructure even at 1100 °C, where the pure HA had a compact non-porous structure. The Ca/P ratio of CLP-doped HA samples was lower than the stoichiometric HA which indicates a partial reduction of stability that is supposed to induce bioresorption capacity. Cytotoxicity tests by WST-8 with Saos-2 cell lines showed that CLP addition into HA has significantly improved cell viability. The HA-CLP nanoceramics are expected to promote bone regeneration due to cell-friendly microstructure and biomimetic composition which can be supported by further in-vivo clinical studies.

Functionally graded triply periodic minimal surface scaffold of HA-Al2O3 via Vat photopolymerization 3D printing

Hydroxyapatite (HA) is widely used in scaffolds due to its high similarity in the composition to natural bone. However, the weak and fragile characteristics of synthetic HA limit its application. The strength of HA can be increased by the incorporation of alumina (Al2O3) to obtain composites with extraordinary compressive strength and biocompatibility. HA-Al2O3 composites with different ratios were prepared by Vat photopolymerization 3D printing, and their shrinkage, porosity, phase composition and biocompatibility were systematically investigated. In addition, the Diamond structure of the scaffold was chosen to achieve the trade-off relationship between compressive strength and porosity. The results suggest that the HA-Al2O3 composite with 20 vol% HA possesses the maximum compressive strength and 60 vol% HA has optimal biocompatibility. A compositional gradient scaffold from 60 vol% HA and 20 vol% HA was proposed to satisfy different needs of the different parts in scaffold for biocompatibility and compressive strength. The HA-Al2O3 gradient scaffold achieves a preferable compressive strength of 13.7 MPa while possessing gradient biocompatibility.

In vivo assessment of marine vs bovine origin collagen-based composite scaffolds promoting bone regeneration in a New Zealand rabbit model

The ability of human tissues to self-repair is limited, which motivates the scientific community to explore new and better therapeutic approaches to tissue regeneration. The present manuscript provides a comparative study between a marine-based composite biomaterial, and another composed of well-established counterparts for bone tissue regeneration. Blue shark skin collagen was combined with bioapatite obtained from blue shark's teeth (mColl:BAp), while bovine collagen was combined with synthetic hydroxyapatite (bColl:Ap) to produce 3D composite scaffolds by freeze-drying. Collagens showed similar profiles, while apatite particles differed in their composition, being the marine bioapatite a fluoride-enriched ceramic.The marine-sourced biomaterials presented higher porosities, improved mechanical properties, and slower degradation rates when compared to synthetic apatite-reinforced bovine collagen. The in vivo performance regarding bone tissue regeneration was evaluated in defects created in femoral condyles in New Zealand rabbits twelve weeks post-surgery. Micro-CT results showed that mColl:BAp implanted condyles had a slower degradation and an higher tissue formation (17.9 ± 6.9 %) when compared with bColl:Ap implanted ones (12.9 ± 7.6 %). The histomorphometry analysis provided supporting evidence, confirming the observed trend by quantifying 13.1 ± 7.9 % of new tissue formation for mColl:BAp composites and 10.4 ± 3.2 % for bColl:Ap composites, suggesting the potential use of marine biomaterials for bone regeneration.