In Vitro and In Vivo Bone Regeneration Assessment of Titanium-Doped Waste Eggshell-Derived Hydroxyapatite in the Animal Model.

In this work, a titanium-doped hydroxyapatite (HAp) scaffold was produced from two different sources (natural eggshell and laboratory-grade reagents) to compare the efficacy of natural and synthetic resources of HAp materials on new bone regeneration. This comparative study also reports the effect of Ti doping on the physical, mechanical, and in vitro as well as in vivo biological properties of the HAp scaffold. Pellets were prepared in the conventional powder metallurgy route, compacted, and sintered at 900 °C, showing sufficient porosity for bony ingrowth. The physical-mechanical characterizations were performed by density, porosity evaluation, XRD, FTIR, SEM analysis, and hardness measurement. In vitro interactions were evaluated by bactericidal assay, hemolysis, MTT assay, and interaction with simulated body fluid. All categories of pellets showed absolute nonhemolytic and nontoxic character. Furthermore, significant apatite formation was observed on the Ti-doped HAp samples in the simulated body fluid immersion study. The developed porous pellets were implanted to assess the bone defect healing in the femoral condyle of healthy rabbits. A 2 month study after implantation showed no marked inflammatory reaction for any samples. Radiological analysis, histological analysis, SEM analysis, and oxytetracycline labeling studies depicted better invasion of mature osseous tissue in the pores of doped eggshell-derived HAp scaffolds as compared to the undoped HAp, and laboratory-made samples. Quantification using oxytetracycline labeling depicted 59.31 ± 1.89% new bone formation for Ti-doped eggshell HAp as compared to Ti-doped pure HAp (54.41 ± 1.93) and other undoped samples. Histological studies showed the presence of abundant osteoblastic and osteoclastic cells in Ti-doped eggshell HAp in contrast to other samples. Radiological and SEM data also showed similar results. The results indicated that Ti-doped biosourced HAp samples have good biocompatibility, new bone-forming ability, and could be used as a bone grafting material in orthopedic surgery.

A practical assessment of nano-phosphate on soybean (Glycine max) growth and microbiome establishment.

The efficacy of needle-shaped nano-hydroxyapatite (nHA; Ca10(PO4)6(OH)2) as a phosphate (Pi) fertilizer was evaluated as well as its impact on soil and soybean (Glycine max) bacterial and fungal communities. Microbial communities were evaluated in soy fertilized with nHA using ITS (internal transcribed spacer) and 16S rRNA high-throughput gene sequencing. Separate greenhouse growth experiments using agriculturally relevant nHA concentrations and application methods were used to assess plant growth and yield compared with no Pi (-P), soluble Pi (+P), and bulk HA controls. Overall, nHA treatments did not show significantly increased growth, biomass, total plant phosphorus concentrations, or yield compared with no Pi controls. Soil and rhizosphere community structures in controls and nHA treatment groups were similar, with minor shifts in the nHA-containing pots comparable to bulk HA controls at equal concentrations. The implementation of nHA in an agriculturally realistic manner and the resulting poor soy growth advises that contrary to some reports under specialized conditions, this nano-fertilizer may not be a viable alternative to traditional Pi fertilizers. If nano-phosphate fertilizers are to achieve their conjectured agricultural potential, alternative nHAs, with differing morphologies, physicochemical properties, and interactions with the soil matrix could be investigated using the evaluative procedures described.

Sinus Floor Augmentation Using Recombinant Human Bone Morphogenetic Protein-2 With Hydroxyapatite: Volume Assessment.

INTRODUCTION: The aim of this study was to assess the efficacy of using bone morphogenetic protein-2 with hydroxyapatite granules (BMP-2/hydroxyapatite) during augmentation of maxillary sinus floor, with respect to changes in volume, relative to conventional bone graft materials. METHOD AND MATERIALS: Twenty of 25 patients in the BMP-2/hydroxyapatite group, and 16 of 33 patients in the conventional materials group met the criteria for inclusion in this study. Computed tomography scans were performed preoperatively, immediately postoperatively, and at follow-up, approximately 6 months postoperatively. Changes in volume and height of both grafted materials were measured using 3-dimensional reconstruction software; these changes were compared between groups. RESULTS: The mean (standard deviation) volumetric changes were 0.25 (0.11) cc and -0.07 (0.35) cc, and the mean rates of volumetric changes were 26.44% (7.78%) and -2.92% (30.92%) in BMP-2/hydroxyapatite and conventional materials groups, respectively. The mean height changes were 0.34 (0.73) mm and -0.63 (1.07) mm, and the mean rates of height changes were 3.67% (7.57%) and -5.95% (9.98%) in BMP-2/hydroxyapatite and conventional materials groups, respectively. CONCLUSION: Compared with the conventional materials group, the BMP-2/hydroxyapatite group showed better maxillary sinus floor augmentation results in terms of volumetric changes and grafted material densities, and can provide predictably reliable outcomes.

In-vivo assessment of minerals substituted hydroxyapatite / poly sorbitol sebacate glutamate (PSSG) composite coating on titanium metal implant for orthopedic implantation.

Currently, bio-mimetic material synthetic processes are involved in bone implant design which is closely related to natural bone. In this work, Zinc, Cerium and Selenium substituted hydroxyapatite/ Poly (sorbitol sebacate glutamate) (Zn, Ce, Se-HAP/PSSG, M-HAP/PSSG) composite was prepared by sol-gel method as a bio-mimetic materials for bone implantation. The physiochemical characterizations of M-HAP/PSSG was analyzed by Fourier transform infra red (FT-IR), X-ray diffraction (XRD), Scanning electron microscopy (SEM) equipped with energy dispersive X-ray analysis (EDX) and High resolution transmission electron microscopy (HRTEM). Then, the prepared M-HAP/PSSG composite was compared with HAP/PSSG, Zn-HAP/PSSG, Ce-HAP/PSSG and Se-HAP/PSSG composites in order to evaluate the influence of single minerals on HAP matrix. Then the coating ability of the final better M-HAP/PSSG composite on surface treated titanium (Ti) was investigated to evaluate the perfection of implant material. The higher micro-hardness was observed on M-HAP/PSSG composite coated Ti (305.92 ±â€¯20.42) due to the presence of multi-minerals as well as the co-polymer PSSG when compared with M-HAP coated Ti plate (273.0 ±â€¯15.75). The bio-compatibility and osteogenic activity evaluation of all prepared composite on human osteoblasts MG-63 cells shows that the better cell attachment, proliferation and differentiation was observed by M-HAP/PSSG bio-composites when compared with other composites. Histological staining and X-ray photographs of in-vivo rat model confirms that the formation of new tibial bone when the defected rat was treated with M-HAP/PSSG composite coated Ti implant. In conclusion, the bio-composite M-HAP/PSSG is better scaffold for coating on the surface of Ti implant for orthopedic implantation.

Engineering a multifunctional 3D-printed PLA-collagen-minocycline-nanoHydroxyapatite scaffold with combined antimicrobial and osteogenic effects for bone regeneration.

3D-printing and additive manufacturing can be powerful techniques to design customized structures and produce synthetic bone grafts with multifunctional effects suitable for bone repair. In our work we aimed the development of novel multifunctionalized 3D printed poly(lactic acid) (PLA) scaffolds with bioinspired surface coatings able to reduce bacterial biofilm formation while favoring human bone marrow-derived mesenchymal stem cells (hMSCs) activity. For that purpose, 3D printing was used to prepare PLA scaffolds that were further multifunctionalized with collagen (Col), minocycline (MH) and bioinspired citrate- hydroxyapatite nanoparticles (cHA). PLA-Col-MH-cHA scaffolds provide a closer structural support approximation to native bone architecture with uniform macroporous, adequate wettability and an excellent compressive strength. The addition of MH resulted in an adequate antibiotic release profile that by being compatible with local drug delivery therapy was translated into antibacterial activities against Staphylococcus aureus, a main pathogen associated to bone-related infections. Subsequently, the hMSCs response to these scaffolds revealed that the incorporation of cHA significantly stimulated the adhesion, proliferation and osteogenesis-related gene expression (RUNX2, OCN and OPN) of hMSCs. Furthermore, the association of a bioinspired material (cHA) with the antibiotic MH resulted in a combined effect of an enhanced osteogenic activity. These findings, together with the antibiofilm activity depicted strengthen the appropriateness of this 3D-printed PLA-Col-MH-cHA scaffold for future use in bone repair. By targeting bone repair while mitigating the typical infections associated to bone implants, our 3D scaffolds deliver an integrated strategy with the combined effects further envisaging an increase in the success rate of bone-implanted devices.

Assessment of bacterial communities in Cu-contaminated soil immobilized by a one-time application of micro-/nano-hydroxyapatite and phytoremediation for 3 years.

Heavy metals contamination of soil has been considered as a global environmental problem, and consequently various soil amendments have been widely used in immobilization. Previous studies have reported that micro-/nano-hydroxyapatite (MHA/NHA) as a novel chemical material could alleviate soil acidity and reduce the bioavailability of heavy metals. However, the mechanism of soil microorganism responding to the application of MHA/NHA is little studied. Presently, an in-situ field experiment was conducted to determine the effects of MHA/NHA and the other three traditional amendments including alkali slag (AS), lime (L) and apatite (AP) on soil copper (Cu) bioavailability and dominate bacterial population. The results showed that the application of MHA/NHA effectively increased soil pH and decreased soil available Cu content, and showed the highest increasing effects on the activities of urease, catalase and acid phosphatase. Compared with the control, MHA/NHA significantly changed the soil bacterial community structure and increased the bacterial abundance and diversity. Besides, analysis of the dominate population showed that the application of MHA/NHA decreased the relative abundance of acidophiles and the indicator of soil degradation. Additionally, the relative abundance of potential plant growth promoting bacteria increased with the addition of MHA/NHA, which was confirmed by the characteristics (the ability of producing indole acetic acid and siderophore) of bacterial strains. These results suggested that these dominate bacterial populations with significant changes may be regarded as the biomarkers for the recovery of soil ecological environment, which provides a theoretical basis for the ecological evaluation of MHA/NHA.

Biocompatibility assessment of graphene oxide-hydroxyapatite coating applied on TiO2 nanotubes by ultrasound-assisted pulse electrodeposition.

In this study, the ultrasound-assisted pulse electrodeposition was introduced to fabricate the graphene oxide (GO)-hydroxyapatite (HA) coating on TiO2 nanotubes. The results of the X-ray diffraction (XRD), Fourier Transform Infrared spectroscope (FTIR), Transmission Electron Microscope (TEM) and micro-Raman spectroscopy showed the successful synthesis of GO. The Scanning Electron Microscope (SEM) images revealed that in the presence of ultrasonic waves and GO sheets a more compact HA-based coating with refined microstructure could be formed on the pretreated titanium. The results of micro-Raman analysis confirmed the successful incorporation of the reinforcement filler of GO into the coating electrodeposited by the ultrasound-assisted method. The FTIR analysis showed that the GO-HA coating was consisted predominantly of the B-type carbonated HA (CHA) phase. The pretreatment of the substrate and incorporation of the GO sheets into the HA coating had a significant effect on improving the bonding strength at the coating-substrate interface. Moreover, the results of the fibroblast cell culture and 3­(4,5­dimethylthiazolyl­2)­2, 5­diphenyltetrazolium bromide (MTT) assay after 2 days demonstrated a higher percentage of cell activity for the GO-HA coated sample. Finally, the 7-day exposure to simulated body fluid (SBF) showed a faster rate of apatite precipitation on the GO-HA coating, as compared to the HA coating and pretreated titanium.

Assessment of tricalcium phosphate/collagen (TCP/collagene)nanocomposite scaffold compared with hydroxyapatite (HA) on healing of segmental femur bone defect in rabbits.

Bone regeneration is an important objective in clinical practice and has been used for different applications. The aim of this study was to evaluate the effectiveness of nanocomposite tricalcium phosphate (TCP)/collagen scaffolds combined with hydroxyapatite scaffold for bone healing in surgery of femoral defects in rabbits. In this study, 45 mature male New Zealand white rabbits between 6 and 8 months old and weighting between 3 and 3.5 kg were examined. Rabbits were divided into three groups. Surgical procedures were performed after intramuscular injection of Ketamine 10% (ketamine hydrochloride, 50 mg/kg) and Rompun 5% (xylazine, 5 mg/kg). Then an approximately 6 mm diameter-5 mm cylinder bone defect was created in the femur of one of the hind limbs. After inducing the surgical wound, all rabbits were coloured and randomly divided into three experimental groups of 15 animals each. Group 1 received pure medical nanocomposite TCP/collagen granules, group 2 received hydroxyapatite, and third group was a control group which received no treatment. Histopathological evaluation was performed on days 15, 30, and 45 after surgery. On days 15, 30, and 45 after surgery, the quantity and the velocity of stages of bone formation at the healing site in nanocomposite TCP/collagen group were better than HA and control groups and the quantity of newly formed lamellar bone at the healing site in nanocomposite TCP/collagen group were better than onward compared with HA and control groups. In conclusion, it seems that TCP/collagen nanocomposite has a significant role in the reconstruction of bone defects and can be used as scaffold in bone fractures.

Why Biphasic? Assessment of the Effect on Cell Proliferation and Expression.

INTRODUCTION: Tricalcium silicate (TCS)-based materials are used in endodontics because they are hydraulic and interact with blood, tissue fluids, and phosphate-based root canal irrigants, resulting in biomineralization. Newer-generation materials are biphasic; calcium phosphate is added to the TCS; thus, the material has 2 cementitious phases. The effect of this addition is not known; thus, the aim of this study was to characterize biphasic cements and assess cellular proliferation and expression. METHODS: TCS cement mixed with calcium phosphate monobasic or hydroxyapatite in 1:1 proportion was prepared. The powders and the mixed cements soaked in Hank's balanced salt solution for 28 days were characterized by scanning electron microscopy (SEM), energy-dispersive spectroscopy, and X-ray diffraction analysis. Ion leaching was investigated using inductively coupled plasma mass spectroscopy. Cellular interaction with material leachate was investigated by exposing human primary osteoblasts to the leachate from the cements. Cell growth and proliferation were determined using methyltetrazolium assay and SEM. RESULTS: The addition of a calcium phosphate phase to tricalcium silicate changed the material hydration with a reduction in pH and calcium ion release in the leachate when calcium phosphate monobasic was added. No crystalline calcium hydroxide was formed for both biphasic materials. The biphasic cements exhibited a reduction in cell growth and proliferation. SEM of the materials showed heavy carbonation of the material surface caused by processing for microscopy. CONCLUSIONS: The addition of a second cementitious phase results in modification of the hydration characteristics of TCS cement with deterioration of material and biocompatibility properties.

Assessment of polycaprolacton (PCL) nanocomposite scaffold compared with hydroxyapatite (HA) on healing of segmental femur bone defect in rabbits.

Segmental bone loss due to trauma, infection, and tumor resection and even non-union results in the vast demand for replacement and restoration of the function of the lost bone. The objective of this study is to utilize novel inorganic-organic nanocomposites for biomedical applications. Biodegradable implants have shown great promise for the repair of bone defects and have been commonly used as bone substitutes, which traditionally would be treated using metallic implants. In this study, 45 mature male New Zealand white rabbits 6-8 months and weighting 3-3.5 kg were examined. Rabbits were divided into three groups. Surgical procedures were done after an intramuscular injection of Ketamine 10% (ketamine hydrochloride, 50 mg/kg), Rompun 5% (xylazine, 5 mg/kg). Then an approximately 6 mm diameter - 5 mm cylinder bone defect was created in the femur of one of the hind limbs. After inducing the surgical wound, all rabbits were colored and randomly divided into three experimental groups of nine animals each: Group 1 received medical pure nanocomposite polycaprolactone (PCL) granules, Group 2 received hydroxyapatite and Group 3 was a control group with no treatment. Histopathological evaluation was performed on days 15, 30 and 45 after surgery. On day 45 after surgery, the quantity of newly formed lamellar bone in the healing site in PCL group was better than onward compared with HA and control groups. Finally, nanocomposite PCL granules exhibited a reproducible bone-healing potential.

A novel one-pot process for near-net-shape fabrication of open-porous resorbable hydroxyapatite/protein composites and in vivo assessment.

We present a mild one-pot freeze gelation process for fabricating near-net, complex-shaped hydroxyapatite scaffolds and to directly incorporate active proteins during scaffold processing. In particular, the direct protein incorporation enables a simultaneous adjustment and control of scaffold microstructure, porosity, resorbability and enhancement of initial mechanical and handling stability. Two proteins, serum albumin and lysozyme, are selected and their effect on scaffold stability and microstructure investigated by biaxial strength tests, electron microscopy, and mercury intrusion porosimetry. The resulting hydroxyapatite/protein composites feature adjustable porosities from 50% to 70% and a mechanical strength ranging from 2 to 6 MPa comparable to that of human spongiosa without any sintering step. Scaffold degradation behaviour and protein release are assessed by in vitro studies. A preliminary in vivo assessment of scaffold biocompatibility and resorption behaviour in adult domestic pigs is discussed. After implantation, composites were resorbed up to 50% after only 4 weeks and up to 65% after 8 weeks. In addition, 14% new bone formation after 4 weeks and 37% after 8 weeks were detected. All these investigations demonstrate the outstanding suitability of the one-pot-process to create, in a customisable and reliable way, biocompatible scaffolds with sufficient mechanical strength for handling and surgical insertion, and for potential use as biodegradable bone substitutes and versatile platform for local drug delivery.

Assessment of the use of LED phototherapy on bone defects grafted with hydroxyapatite on rats with iron-deficiency anemia and nonanemic: a Raman spectroscopy analysis.

This study aimed to assess bone repair in defects grafted or not with hydroxyapatite (HA) on healthy and iron-deficiency anemia (IDA) rats submitted or not to LED phototherapy (LED-PT) by Raman spectroscopy. The animals were divided in eight groups with five rats each: Clot; Clot + LED; IDA + Clot; IDA + LED; Graft; Graft + LED; IDA + Graft; and IDA + Graft + LED. When appropriated, irradiation with IR LED (λ850 ± 10 nm, 150 mW, CW, Φ = 0.5 cm(2), 16 J/cm(2), 15 days) was carried out. Raman shifts: ∼ 960 [symmetric PO4 stretching (phosphate apatite)], ∼ 1,070 [symmetric CO3 stretching (B-type carbonate apatite)], and ∼ 1,454 cm(-1) [CH2/CH3 bending in organics (protein)] were analyzed. The mean peak values for ∼ 960, ∼ 1,070, and ∼ 1,454 cm(-1) were nonsignificantly different on healthy or anemic rats. The group IDA + Graft + LED showed the lowest mean values for the peak ∼ 960 cm(-1) when compared with the irradiated IDA group or not (p ≤ 0.001; p ≤ 0.001). The association of LED-PT and HA-graft showed lowest mean peak at ∼ 1,454 cm(-1) for the IDA rats. The results of this study indicated higher HA peaks as well as a decrease in the level of organic components on healthy animals when graft and LED phototherapy are associated. In the other hand, IDA condition interfered in the graft incorporation to the bone as LED phototherapy only improved bone repair when graft was not used.

Relevance of the sterilization-induced effects on the properties of different hydroxyapatite nanoparticles and assessment of the osteoblastic cell response.

Hydroxyapatite (Hap) is a calcium phosphate with a chemical formula that closely resembles that of the mineral constituents found in hard tissues, thereby explaining its natural biocompatibility and wide biomedical use. Nanostructured Hap materials appear to present a good performance in bone tissue applications because of their ability to mimic the dimensions of bone components. However, bone cell response to individual nanoparticles and/or nanoparticle aggregates lost from these materials is largely unknown and shows great variability. This work addresses the preparation and characterization of two different Hap nanoparticles and their interaction with osteoblastic cells. Hap particles were produced by a wet chemical synthesis (WCS) at 37°C and by hydrothermal synthesis (HS) at 180°C. As the ultimate in vivo applications require a sterilization step, the synthesized particles were characterized 'as prepared' and after sterilization (autoclaving, 120°C, 20 min). WCS and HS particles differ in their morphological (size and shape) and physicochemical properties. The sterilization modified markedly the shape, size and aggregation state of WCS nanoparticles. Both particles were readily internalized by osteoblastic cells by endocytosis, and showed a low intracellular dissolution rate. Concentrations of WCS and HS particles less than 500 µg ml(-1) did not affect cell proliferation, F-actin cytoskeleton organization and apoptosis rate and increased the gene expression of alkaline phosphatase and BMP-2. The two particles presented some differences in the elicited cell response. In conclusion, WCS and HS particles might exhibit an interesting profile for bone tissue applications. Results suggest the relevance of a proper particle characterization, and the interest of an individual nanoparticle targeted research.

Human periodontal ligament fibroblasts stimulated by nanocrystalline hydroxyapatite paste or enamel matrix derivative. An in vitro assessment of PDL attachment, migration, and proliferation.

We determined the effects of soluble or coated nanocrystalline hydroxyapatite paste (nano-HA) and enamel matrix derivative (EMD) on proliferation, adhesion, and migration of periodontal ligament fibroblasts (PDLs). Cultured PDLs were stimulated with nano-HA paste or EMD in a soluble form or were coated to the surface of cell culture dishes. Proliferation of PDLs on coated nano-HA and EMD was quantified by various methods including bromodeoxyuridine (BrdU) incorporation and Western blot. Cell migration was investigated in a modified Boyden chamber. The surface integrin profile of PDLs was determined using an integrin-specific ELISA, and integrin-specific signaling was measured by immunoblotting of phosphorylated focal adhesion kinase (FAK). Coated nano-HA stimulated PDL proliferation to a larger extent as compared with coated EMD. PDL migration towards a nano-HA or EMD gradient was more efficiently mediated by soluble EMD as compared with nano-HA but vice versa, adhesion of PDLs to compound-coated dishes was more effectively mediated by nano-HA as compared with EMD. Mechanistically, majorly integrin α5ß1-mediated adhesion of PDL and both coated compounds mediated a significant increase in FAK activation though to a different extent. Current findings offer two different modes of action for EMD and nano-HA paste. EMD efficiently acts as a chemoattractant in its soluble form, while nano-HA paste effectively serves as a synthetic extracellular matrix component in its coated form. Our findings suggest that EMD and nano-HA paste display different molecular characteristics and apply alternative routes to mediate their beneficial effects on periodontal tissues.

Bactericidal activity and in vitro cytotoxicity assessment of hydroxyapatite containing gold nanoparticles.

Hydroxyapatite (HA) containing gold (Au) nanoparticles was synthesized for the biomedical applications. The morphology, structure and thermal properties of the HA containing Au nanoparticles were characterized by field emission scanning electron microscopy (FE-SEM), transmission electron microscopy (TEM), energy dispersive X-ray (EDX) spectroscopy, X-ray diffraction (XRD), Fouriertransform infrared spectroscopy (FT-IR) and thermogravimetry (TGA). XRD patterns clearly revealed the formation of HA-Au composite nanoparticles. TEM observation showed that the Au nanoparticles had an average size of 5 nm and were incorporated into HA powder very well. Bactericidal activity of HA-Au with Au nanoparticles immobilized in HA was investigated. The adhesion, viability and proliferation properties of HA containing Au nanoparticles and the differentiation of osteoblast were studied for in vitro cell compatibility of the HA containing Au nanoparticles. Our results showed that HA containing Au nanoparticles were cytotoxic to the human osteoblastic cells.

Biological and physico-chemical assessment of hydroxyapatite (HA) with different porosity.

HA with specific internal porosities was loaded with different antibiotics (ATBs) and then tested on its microbiological effectiveness. The HA purity was controlled with X-ray diffraction, IR and Raman spectrometry. Varying the sintering temperature and/or adding graphite and PMMA as porogenous agents lead to obtained micro- and meso-porosities. The biological tests concerned cell viability, proliferation and morphology (SEM), and the cytochemical staining of actin and vinculin. The micro- and meso-porous HA samples had an internal pore size of 1-10 microm and 10-50 microm, respectively. X-ray diffraction and FTIR confirmed the high purity of the HA. The cell viability tests with L132 cells confirmed the excellent cytocompatibility of HA, the graphite powder and the ATB vancomycine. Proliferation rate was assessed with MC3T3-E1 osteoblasts. All HA samples produced a higher proliferation than the controls; the micro-porous HA inducing the highest cell growth. The ATB impregnated HA also stimulated cell proliferation but in lower extend. Cytochemical staining of osteoblasts revealed a well-developed cytoskeleton with strong stress fibres. Labelling of the focal adhesion contacts with anti-vinculin showed a less developed adhesion process in the cells on the different HA substrates. It was possible to realize a highly pure hydroxyapatite with different but controlled porosities by varying the sintering temperature and/or addition of a porogenous agents. This purity and the micro-porosity stimulate significantly cell growth.

Biological assessment of the bone-screw interface after insertion of uncoated and hydroxyapatite-coated pedicular screws in the osteopenic sheep.

The sheep seems to be a promising model of osteoporosis and biomaterial osteointegration in osteopenic bone. The long-term ovariectomized sheep model was used for the biological investigation of bone healing around uncoated and hydroxyapatite (HA)-coated pedicle screws in osteopenic bone. Four sheep were ovariectomized and four sheep were sham-operated. Twenty-four months after surgery, the animals were implanted with uncoated and HA-coated stainless steel screws in the lumbar vertebral pedicles. Four months later, bone-to-implant contact, bone ingrowth, and bone hardness were measured around screws. Uncoated stainless steel presented significantly (p < 0.0005) lower bone-to-implant contact in healthy and osteopenic bone compared with HA-coated stainless steel. HA significantly improved bone ingrowth in healthy bone (p < 0.05) compared with uncoated stainless steel. Osteopenia significantly (p < 0.05) reduced the area of bone ingrowth around the screw threads for both types of implants. In the inner thread area, bone microhardness significantly increased (p < 0.05) in HA-coated surface versus uncoated for healthy and osteopenic bone. HA coating significantly enhances bone-to-implant contact also in osteopenic bone in comparison with uncoated stainless steel surfaces. Bone ingrowth and mineralization are ameliorated by the osteoconductive HA coating. However, osteopenia seems to greatly influence bone ingrowth processes around the implanted screws regardless of the characteristics of the material surface.