Hydroxyapatite Microparticles Research Articles

Poly(dl-lactide) Polymer Blended with Mineral Phases for Extrusion 3D Printing-Studies on Degradation and Biocompatibility.

A promising therapeutic option for the treatment of critical-size mandibular defects is the implantation of biodegradable, porous structures that are produced patient-specifically by using additive manufacturing techniques. In this work, degradable poly(DL-lactide) polymer (PDLLA) was blended with different mineral phases with the aim of buffering its acidic degradation products, which can cause inflammation and stimulate bone regeneration. Microparticles of CaCO3, SrCO3, tricalcium phosphates (α-TCP, β-TCP), or strontium-modified hydroxyapatite (SrHAp) were mixed with the polymer powder following processing the blends into scaffolds with the Arburg Plastic Freeforming 3D-printing method. An in vitro degradation study over 24 weeks revealed a buffer effect for all mineral phases, with the buffering capacity of CaCO3 and SrCO3 being the highest. Analysis of conductivity, swelling, microstructure, viscosity, and glass transition temperature evidenced that the mineral phases influence the degradation behavior of the scaffolds. Cytocompatibility of all polymer blends was proven in cell experiments with SaOS-2 cells. Patient-specific implants consisting of PDLLA + CaCO3, which were tested in a pilot in vivo study in a segmental mandibular defect in minipigs, exhibited strong swelling. Based on these results, an in vitro swelling prediction model was developed that simulates the conditions of anisotropic swelling after implantation.

3D stem cell spheroids with urchin-like hydroxyapatite microparticles enhance osteogenesis of stem cells.

Cell therapy (also known as cell transplantation) has been considered promising as a next-generation living-cell therapy strategy to surpass the effects of traditional drugs. However, their practical clinical uses and product conversion are hampered by the unsatisfied viability and efficacy of the transplanted cells. Herein, we propose a synergistic enhancement strategy to address these issues by constructing 3D stem cell spheroids integrated with urchin-like hydroxyapatite microparticles (uHA). Specifically, cell-sized uHA microparticles were synthesized via a simple hydrothermal method using glutamic acid (Glu, E) as the co-template with good biocompatibility and structural antimicrobial performance (denoted as E-uHA). Combining with a hanging drop method, stem cell spheroids integrated with E-uHA were successfully obtained by culturing bone marrow mesenchymal stem cells (BMSCs) with a low concentration of the E-uHA suspensions (10 μg mL-1). The resulting composite spheroids of BMSCs/E-uHA deliver a high cellular viability, migration activity, and a superior osteogenic property compared to the 2D cultured counterpart or other BMSC spheroids. This work provides an effective strategy for integrating a secondary bio-functional component into stem cell spheroids for designing more cell therapy options with boosted cellular viability and therapeutic effect.

Chitosan/PVA reinforced boron/strontium multi-substituted hydroxyapatite-based biocomposites: Effects of synthesis pH and coating on the physicochemical, mechanical, and in vitro biological properties of scaffolds

Bioceramics are used in hard tissue applications to repair and replace damaged parts inside the human body. Hydroxyapatite (HAp) is the most widely used bioceramic due to its ability to bind to hard tissues. Furthermore, enhancing the bioactivity of HAp in hard tissue applications through co-substituted particles is of great interest. In this study, different types of HAp microparticles, including unsubstituted, boron-substituted (B-HAp), strontium-substituted (Sr-HAp), boron and strontium co-substituted HAp (B–Sr-HAp) were synthesized at pH 9 and 11 using the wet precipitation method. The impact of synthesis pH on the chemical composition and crystalline structure of the microparticles was investigated. Sintered porous three-dimensional ceramic scaffolds were prepared, polyvinyl alcohol (PVA) and chitosan (Chi) were chosen to improve the mechanical properties of the ceramic scaffolds owing to their biocompatibility and functional groups. In vitro cytotoxicity and in vitro hemocompatibility studies were conducted to evaluate the biocompatibility of the constructs. The results revealed that synthesis pH of 11 yielded the highest substitution without altering the crystalline phase. Also, the PVA/Chi coating improved the compressive strength of all scaffolds, with the most significant improvement observed in Br-HAp due to borate-diol complexation at the ceramic-polymer interface. Preliminary in vitro studies revealed that scaffolds were non-cytotoxic and hemocompatible.

Effects of Anti-Sclerostin Antibody Release from Porous Microparticles on Bone Resorption Inhibition of Osteoblasts

Background: Anti-sclerostin antibodies are among the most efficient drugs for the treatment of osteoporosis, and have been also expected for the treatment of local bone disorders. We have previously developed porous microparticles of hydroxyapatite and chondroitin sulfate loading anti-sclerostin antibodies formulated with zinc cations. However, the biological behavior and con-centration dependence of anti-sclerostin antibodies in vitro released from the microparticles remain unclear. Objective: Bolus administration and the subsequent release of anti-sclerostin antibodies from the microparticles formulated with or without zinc cations were investigated; bone-resorptive inhibitory effects on mouse MC3T3-E1 osteoblast function were revealed by cell culture using a cell culture insert plate. Methods: Differentiation induction culture of osteoblasts was performed after maintaining the concentrations of anti-sclerostin antibodies and sclerostin at previously reported concentrations of 5.0 and 1.0 µg/mL for the first 3 days. Subsequently, the medium was replaced with fresh medium that did not contain anti-sclerostin antibodies but microparticles loading anti-sclerostin antibodies (20 or 80 µg/mg) with or without zinc cations in the cell culture insert. After 11 days of incubation, the bioactivity of the osteoblasts was evaluated using the polymerase chain reaction method. Results: The formulation using zinc cations showed an increase of anti-sclerostin antibodies re-leased from the microparticles, which increased the expression of receptor activator of the nuclear factor kappa-B ligand in the osteoblasts on day 14. This result indicates the inhibition of sclerostin-mediated bone resorption. However, the increase of loading amounts of anti-sclerostin antibodies extremely enhanced the subsequent release of anti-sclerostin antibodies, which decreased the inhibition of bone resorption contrary to expectations. Conclusion: The moderately sustained release of anti-sclerostin antibodies from the microparticles can promote the inhibition of bone resorption in osteoblasts, supporting the potential of this formulation for the treatment of localized bone disorders.

Atmospheric plasma spray coating of antibacterial nano silver-hydroxyapatite on titanium surface for biomedical applications

ABSTRACT In this paper, the nanosilver particles were deposited onto the hydroxyapatite (HAP) microparticles and the obtained nanoAg-HAP particles were coated onto the Ti metal surface using the atmospheric plasma spray method. Then, the obtained nanoAg-HAP coating on Ti substrate was annealed at 700°C. The antibacterial activities of the nanoAg-HAP coatings on Ti were also tested against the microorganisms. The prepared nanoAg-HAP particles were examined using the optic microscopy, FE-SEM, HR-TEM, XRD and the UV-vis. absorption spectroscopy methods. The nanoAg particles exhibited crystalline spherical morphologies with the particle sizes below 30 nm. In the FE-SEM-EDS measurements, well distribution of nanoAg particles on the HAP microparticles were observed with Ag concentrations of 0.153% and 0.313%. The HR-TEM measurements showed that the nanoAg particles have hexagonal close packing (hcp) crystal structure with the d-spacing values of 0.23 nm (111), 0.21 nm (002) and 0.14 nm (022). After 700°C heat treatment, the prepared nanoAg-HAP coating on Ti metal showed 100% antibacterial activity against E. coli and S. epidermidis bacteria. As a result, the obtained nanoAg-HAP coated Ti metal can be utilized effectively as a self-disinfecting biomedical implant material in the orthopedic bone repairing of the body parts.

339 Mineral Coated Micropaarticles Delivering Chondroitinase ABC mRNA Improves Motor Function After Spinal Cord Injury in Rats

INTRODUCTION: Currently, there are no treatments to help regain a significant amount of the function that is lost after spinal cord injury (SCI). A primary reason for the lack in functional recovery is the glial scar, which forms after SCI and inhibits axonal regeneration. Chondroitinase ABC (ChABC), a bacterial enzyme, digests one of the main axonal inhibitors in the glial scar, chondroitin sulfate proteoglycans (CSPGs), and results in axonal regeneration and functional recovery. However, ChABC is not thermally stable and quickly becomes inactive at body temperature. Recently, messenger RNA (mRNA) delivery has emerged as an attractive strategy for non-virally producing proteins in vivo with higher activity than recombinant proteins and a more desirable safety profile than viral gene delivery. METHODS: ChABC mRNA synthesis was designed in Benchling Molecular Biology Suite and ordered as-synthesized plasmid (Genscript). Mineral coatings were grown on hydroxyapatite microparticles and lipoplexes with mRNA were bound to the coatings. Rat spinal cords were contused at the T10 level and the glial scar was allowed to form. Seven days post-injury MCMs with ChABC mRNA were injected into the epicenter of the injury. Rat Hindlimb function was assessed for seven weeks before the rats were harvested. Lastly, immunohistochemistry was used to assess CSPG digestion and axonal sprouting. RESULTS: MCMs delivering ChABC mRNA forced local overexpression of ChABC and significantly digested CSPGs after SCI, resulting in axonal sprouting and a significant improvement in hindlimb function. CONCLUSIONS: MCMs efficiently delivered ChABC mRNA to digest CSPGs in the glial scar after SCI.

Effect of Different Biomimetic Materials on White Spot Lesions in Enamel (A split-mouth clinical trial)

Purpose: To assess the remineralizing effect and clinical effectiveness of different biomimetic materials (Zinc carbonate hydroxyapatite microparticles (Zn CHA), bioactive glass nanoparticles (BAG) and Poly-amido amine (PAMAM)) on white spot lesions in enamel (WSLs). Materials and Methods: A number of 84 teeth (21 patients) were assigned into 3 groups of 28 teeth (7 patients) in accordance to the time of assessment (immediately B1, after one-month B2 and after two months B3). According to the tested material; every patient had a split mouth (four quadrants). Zn CHA was used in the first group A1, BAG was used in the second group A2, PAMAM was used for the third groupA3, whereas in the fourth group A4; no treatment was carried out (control). Standardized periapical radiographs were obtained for assessment of re-mineralization using measurements of radiodensity (%). Standardized digital photography was obtained for colour change assessment. Results: The change between the study groups has statistical significance (pvalue=0.00) at all times grouping (for Radiodensity % and the colour changes). Moreover; results revealed nonsignificant change between BAG and PAMAM groups (at all time groups). Also; difference between Zn CHA and BAG was not statistically significant at two months only (Radiodensity %). Conclusions: All the tested materials have a remineralizing effect and improved the appearance of the WSLs. Zn-CHA needs longer time (2 months) as a biomimetic remineralizing agent. Time is an important issue for biomimetic re-mineralization. Biomimetic re-mineralization can be achieved by regular use of biomimetic toothpaste.

Comparative Study of Injectable Implants Based on Microparticles of Various Biodegradable Materials in a Murine Model of Subcutaneous Implantation

A comparative study of two commercially available injectable implants based on microparticles of various biodegradable materials (calcium hydroxyapatite and cross-linked collagen) was carried out using a murine model of subcutaneous implantation. The developed experimental model showed that both implants effectively replace the volume of soft tissues. Implant resorption was accompanied by a moderate chronic inflammatory response. The implant based on calcium hydroxyapatite microparticles caused pronounced post-injection swelling at 1 day after administration and demonstrated a more pronounced migration from the injection point. For this implant, an earlier onset of the process of replacing microparticles with autologous collagen fibers, accompanying its biodegradation, was observed. The implant based on cross-linked collagen microparticles had a greater lifting effect at the injection site and retained a longer effect of skin augmentation lasting for 12 months.

THE USE OF BIOMIMETIC NANOCRYSTALS ZN-CARBONATE HYDROXYAPATITE IN THE TREATMENT OF LOCALIZED HYPERSENSITIVITY OF HARD TISSUES OF TEETH

Abstract: The problem of hypersensitivity of hard tissues of teeth remains relevant in modern dentistry to this day. Despite the fact that the market of dental products is saturated with ultramodern means to reduce the sensitivity of hard tissues of teeth, the issue associated with the relief of pain remains open. To develop a new approach to solving this problem, localized hypersensitivity of the 2nd degree of hard dental tissues was treated in 40 patients aged 20 to 45 years of both sexes. According to the concept of biomimetic/bioemulation, which became the scientific basis for the study, a toothpaste containing a mixture of bioactive microparticles of carbonate hydroxyapatite with zinc-substituted, similar to the structure of human teeth (biomimetic nanocrystals microRepair®) was used. There was a statistically significant prolonged decrease in the sensitivity of hard tooth tissues when using professional toothpaste with bioactive microparticles, provided its combined use in clinical conditions and at home, with daily use in the form of brushing teeth, compared with its single-component application at a specialist's appointment.

Fabrication of novel kaolin-reinforced hydroxyapatite scaffolds with robust compressive strengths for bone regeneration

In this study, hydroxyapatite (HAp) microparticles obtained from animal bones were synthesized, and for the first time, HAp was reinforced with beneficiated kaolin using the sol-gel route to improve the mechano-biological properties of the bioceramic materials. The non-reinforced HAp as well as the reinforced samples (K-HAp) were sintered at 900, 1000 and 1100 °C to consolidate the mixture and detailed physico-chemical and mechanical characterizations was conducted. In-vitro experiments in phosphate buffer saline and simulated body fluid were used to confirm the degradability and compatibility of the HAp-derived bioceramic materials, respectively. XRD signatures showed that a dominant phase of hydroxyapatite was formed at all sintering temperatures (900, 1000, 1100 °C). The calcium to phosphate ratio (Ca/P) of the K-HAp-900 sample was approximately 1.67, which is the Ca/P ratio for stoichiometric hydroxyapatite prepared from synthetic sources. The active surface areas of the produced kaolin reinforced bioceramic materials: K-HAp 900–1100,were 0.9770, 0.2159 and 0.8659 m2/g, respectively, while the obtained micropore volumes were 0.000397, 0.001287, and 0.000334 cm3/g, respectively. At 900, 1000 and 1100 °C, compressive strengths (after applying the compaction pressure) with a value of 5.67, 6.33 and 7.66 MPa were obtained for the kaolin reinforced bioceramic materials, respectively. The mechanical measurement data further confirms that the reinforced bioceramic materials are suitable for human trabecular bone as the proposed scaffolds were endowed with an improved mechanical strength matching the bearable range of trabecular bone (2–12 MPa). In-vitro experiments showed the degradability and compatibility of the scaffolds. A relative neutral pH was maintained for sample K-HAp 900, and this sample also showed inhibitory potentials for bacterial strain (E. Coli).

Compressive Strength of Conventional Glass Ionomer Cement Modified with TiO2 Nano-Powder and Marine-Derived HAp Micro-Powder.

The aim of this research was to investigate the compressive strength (CS), breaking strength (BS), and compressive modulus (CM) of conventional glass ionomer cement (GIC) modified with TiO2 nano particles, marine-derived hydroxyapatite (md-HAp) microparticles (<45 µm), and a combination of TiO2 NP and md-HAp particles. The materials used in the study were conventional GIC Fuji IX GP Extra (GC Corporation, Tokyo, Japan), TiO2 powder P25 (Degussa, Essen, Germany), and HAp synthesized from cuttlefish bone and ground in a mortar to obtain md-HAp powder. md-HAp was characterized using FTIR and SEM analysis. There were four groups of GIC samples: (i) Fuji IX control group, (ii) powder modified with 3 wt% TiO2, (iii) powder modified with 3 wt% HAp, and (iv) powder modified with 1.5 wt% TiO2 + 1.5 wt% HAp. Measurements were performed in a universal testing machine, and CS, BS, and CM were calculated. Statistical analysis was performed using ANOVA and Tukey’s tests. CS, BS, and CM differed significantly between the Fuji IX control group and all experimental groups while differences between the experimental groups were not statistically significant. The addition of TiO2 NP, md-HAp micro-sized particles, and a combination of TiO2 and md-HAp reduced the CS, BS, and CM of conventional GICs when mixed at the powder/liquid (p/l) ratio recommended by the manufacturer.

Whitlockite-Enabled Hydrogel for Craniofacial Bone Regeneration.

Growth-factor-free bone regeneration remains a challenge in craniofacial engineering. Here, we engineered an osteogenic niche composed of a commercially modified alginate hydrogel and whitlockite microparticles (WHMPs), which impart tunable physicochemical properties that can direct osteogenesis of human gingival mesenchymal stem cells (GMSCs). Our in vitro studies demonstrate that WHMPs induce osteogenesis of GMSCs more effectively than previously demonstrated hydroxyapatite microparticles (HApMPs). Alginate-WHMP hydrogels showed higher elasticity without any adverse effects on the viability of the encapsulated GMSCs. Moreover, the alginate-WHMP hydrogels upregulate the mitogen-activated protein kinase (MAPK) pathway, which in turn orchestrates several osteogenic markers, such as RUNX2 and OCN, in the encapsulated GMSCs. Concurrent coculture studies with human osteoclasts demonstrate that GMSCs encapsulated in alginate-WHMP hydrogels downregulate osteoclastic activity, potentially due to release of Mg2+ ions from the WHMPs along with secretion of osteoprotegerin from the GMSCs. In vivo studies demonstrated that the GMSCs encapsulated in our osteogenic niche were able to promote bone repair in calvarial defects in murine models. Altogether, our results confirmed the development of a promising treatment modality for craniofacial bone regeneration based on an injectable growth-factor-free hydrogel delivery system.

In situ printing of scaffolds for reconstruction of bone defects

Bone defects are commonly caused by traumatic injuries and tumor removal and critically sized defects overwhelm the regenerative capacity of the native tissue. Reparative strategies such as auto, xeno, and allografts have proven to be insufficient to reconstruct and regenerate these defects. For the first time, we introduce the use of handheld melt spun three dimensional printers that can deposit materials directly within the defect site to properly fill the cavity and form free-standing scaffolds. Engineered composite filaments were generated from poly(caprolactone) (PCL) doped with zinc oxide nanoparticles and hydroxyapatite microparticles. The use of PCL-based materials allowed low-temperature printing to avoid overheating of the surrounding tissues. The in situ printed scaffolds showed moderate adhesion to wet bone tissue, which can prevent scaffold dislocation. The printed scaffolds showed to be osteoconductive and supported the osteodifferentiation of mesenchymal stem cells. Biocompatibility of the scaffolds upon in vivo printing subcutaneously in mice showed promising results. Statement of significance•Bone defects are frequent and, in many cases, benefit from an immediate intervention.•A portable and handheld printer is introduced that allows the printing of hard polymeric materials directly into the defect site that allow reconstruction of the geometrical features of the defected tissue.•The ease-of-use of the investigated device was demonstrated both in vitro and in vivo.•The in situ printed scaffolds adhered to the tissue and supported the growth and differentiation of cultured stem cells. They also prevented bacterial growth without inducing excessive inflammation.

Preparation and biodegradable properties of hydroxyapatite nanoparticle composite coated with poly lactic-co-glycolic acid/polyvinyl alcohol for bone regeneration.

Bone loss rapidly increases 6 months post tooth extraction, which causes the atrophy of the alveolar bone. Two kinds of biomaterials which can stimulate bone regeneration are bioceramics and polymers. Making a composite of biomaterials results in better physical and biomolecular characteristics in comparison with a bioceramic or a polymer alone. Hydroxyapatite nanoparticles (HANPs) are one of the bioceramics commonly used for bone regeneration; they can degrade faster than hydroxyapatite (HA) microparticles, but have an insufficient pore size. Polyvinyl alcohol (PVA) and poly lactic-co-glycolic acid (PLGA) are polymers which have been used for biomedical applications. However, PLGA alone has insufficient cell attachment and PVA alone slowly degrades in the bone tissue. The aim of the present study was to analyze the biodegradation properties of the HANP/PLGA/PVA composites and investigate the pore size. The HANP/PLGA/PVA composites were prepared using the freeze-drying method, with 20% (w/w) of HANP and 20% (w/w) of PLGA. Morphology and the pore size were determined by means of the field emission scanning electron microscopy (FE-SEM) analysis. Biodegradation properties were determined by calculating water uptake and water loss for 1, 3 and 6 weeks. Statistical analysis was performed based on the one-way analysis of variance (ANOVA) at p < 0.05. The HANP/PLGA/PVA composites had the greatest mean pore size and a rougher surface than others (176.00 ±61.93 μm; p < 0.05). Moreover, the HANP/PLGA/PVA composites had the greatest water uptake, significantly in the 3rd (730.46%; p < 0.05) and 6th weeks (731.07%; p < 0.05), and water loss in the 6th week (67.69%; p < 0.05). The HANP/PLGA/PVA composites have optimal pore size, morphology and degradability, which shows their high potential as an effective bone scaffold to repair the alveolar defect post tooth extraction.

Sustained delivery of vascular endothelial growth factor from mesoporous calcium-deficient hydroxyapatite microparticles promotes in vitro angiogenesis and osteogenesis.

Promoting the growth of blood vessels within engineered tissues remains one of the main challenge in bone tissue engineering. One way to improve angiogenesis is the use of vascular endothelial growth factor (VEGF) as it holds the ability to increase the formation of a vascular network. In the present study, collagen scaffolds with VEGF-releasing hydroxyapatite particles were fabricated, in order to engineer a material both capable of presenting an osteoconductive surface and delivering an angiogenic growth factor in a localized and sustained manner, in order to enhance osteogenesis as well as angiogenesis. To this end, we developed microparticles and characterize their size, chemical properties and Ca/P ratio to validate the formation of hydroxyapatite. We then evaluated the osteogenic potential of HAp when cultured with mesenchymal stem cells and compare it to commercially available hydroxyapatite (SBp). Finally, we characterized the encapsulation and release of VEGF in the HAp and assess the angiogenic potential of the VEGF-HAp when cultured with endothelial cells. We demonstrated the successful fabrication of calcium deficient hydroxyapatite microparticles (CDHAp), with biological properties closer to the bone than stoichiometric, commercially available hydroxyapatite. This CDHAp exhibited a well-defined 3D network of crystalline nanoplates forming mesoporous and hollow structures. The high specific area created by those structures enabled the loading of VEGF with high efficiency when compared to the loading efficiency of SBp. Furthermore, their biological performances were evaluated in vitro. Our results indicate that VEGF-CDHAp can be used to improve both osteogenesis and angiogenesis in vitro.

Mechanical measurements of pure and kaolin reinforced hydroxyapatite-derived scaffolds: A comparative study

This study describes the mechanical properties of pure hydroxyapatite (HAp) and kaolin reinforced hydroxyapatite (K-HAp) produced from non-separated animal bones using compression pressure under different sintering regimes. The HAp microparticles were synthesized separately using a facile heat treatment method and reinforced with 15 wt% of beneficiated kaolin (HAp/15 wt% BK) using the sol–gel method. The HAp and K-HAp derived scaffolds were fabricated by cold pressing with a compaction pressure of 500 Pa. Next, the scaffolds were sintered at 900 °C, 1000 °C and 1100 °C with a 2 h dwell time in air atmosphere. Subsequently, the mechanical properties of the scaffolds were examined. The effect of sintering temperature and compaction pressure on the hardness and the compressive strength of the pure and reinforced HAp showed that at all points of measurement (with and without compaction pressure), the mechanical properties increased with an increase in sintering temperature, and the most significant mechanical properties were obtained at 1100 °C. The values of hardness at the maximum sintering temperature (1100 °C) are 0.93 and 1.09 GPa with and without the application of compaction pressure, respectively, for pure HAp-derived scaffolds and 0.74 and 0.78 GPa with and without the application of compaction pressure, respectively, for K-HAp-derived scaffolds. The compressive strength for K-HAp had the value of 7.84 MPa as compared with 0.69 MPa for the non-reinforced HAp matrix with the application of compaction pressure (500 Pa). The findings show that the mechanical properties of the synthesized kaolin reinforced HAp in relation to the scaffolds produced with the low compaction pressure of 500 Pa is suitable for human trabecular bone.

Bio-based composites from plant based precursors and hydroxyapatite with shape-memory capability

A series of bio-based composites consisting of degradable thermoset poly[xylitol-(1,12-dodecanedioate)] (PXD) and hydroxyapatite microparticles (HA) was prepared. Equimolar amounts of xylitol and 1,12-dodecanedioic acid were reacted under catalyst-free polyesterification and the synthesized composites (PXDHCy) consist HA particles ranging between 0 wt% and 20 wt%. Crystallinity of the polymer matrix decreased at low content of HA (5 wt%) as the microparticles hindered crystallization of 1,12-dodecanedioate segment and then increased when the content of HA was raised (from 10 wt% to 20 wt%) as the polymer chains crystallized on surface of microparticles. All PXD and PXDHCy are able to hydrolytically degrade with around 7 wt% to 20 wt% mass loss after 16 weeks incubation in water (rate depends on HA content). The capability of PXD and PXDHCy composites to keep a temporary shape after a deformation process correlated with the polymer crystallinity whereas the shape recovery was 99%. The switching temperatures of PXD and PXDHCy composites ranged around 50 °C (and correlated to the melting-transition temperature) and did not vary with the loading of HA. A prototype of PXDHCy composite smart fixation plug was demonstrated and showed excellent potential to be used as bio-based fixation device for household appliances.

An engineered cell-laden adhesive hydrogel promotes craniofacial bone tissue regeneration in rats.

Cell-laden hydrogels are widely used in tissue engineering and regenerative medicine. However, many of these hydrogels are not optimized for use in the oral environment, where they are exposed to blood and saliva. To address these challenges, we engineered an alginate-based adhesive, photocrosslinkable, and osteoconductive hydrogel biomaterial (AdhHG) with tunable mechanical properties. The engineered hydrogel was used as an injectable mesenchymal stem cell (MSC) delivery vehicle for craniofacial bone tissue engineering applications. Subcutaneous implantation in mice confirmed the biodegradability, biocompatibility, and osteoconductivity of the hydrogel. In a well-established rat peri-implantitis model, application of the adhesive hydrogel encapsulating gingival mesenchymal stem cells (GMSCs) resulted in complete bone regeneration around ailing dental implants with peri-implant bone loss. Together, we have developed a distinct bioinspired adhesive hydrogel with tunable mechanical properties and biodegradability that effectively delivers patient-derived dental-derived MSCs. The hydrogel is photocrosslinkable and, due to the presence of MSC aggregates and hydroxyapatite microparticles, promotes bone regeneration for craniofacial tissue engineering applications.

Rare-earth (Gd3+,Yb3+/Tm3+, Eu3+) co-doped hydroxyapatite as magnetic, up-conversion and down-conversion materials for multimodal imaging

Taking advantage of the flexibility of the apatite structure, nano- and micro-particles of hydroxyapatite (HAp) were doped with different combinations of rare earth ions (RE3+ = Gd, Eu, Yb, Tm) to achieve a synergy among their magnetic and optical properties and to enable their application in preventive medicine, particularly diagnostics based on multimodal imaging. All powders were synthesized through hydrothermal processing at T ≤ 200 °C. An X-ray powder diffraction analysis showed that all powders crystallized in P63/m space group of the hexagonal crystal structure. The refined unit-cell parameters reflected a decrease in the unit cell volume as a result of the partial substitution of Ca2+ with smaller RE3+ ions at both cation positions. The FTIR analysis additionally suggested that a synergy may exist solely in the triply doped system, where the lattice symmetry and vibration modes become more coherent than in the singly or doubly doped systems. HAp:RE3+ optical characterization revealed a change in the energy band gap and the appearance of a weak blue luminescence (λex = 370 nm) due to an increased concentration of defects. The “up”- and the “down”-conversion spectra of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders showed characteristic transitions of Tm3+ and Eu3+, respectively. Furthermore, in contrast to diamagnetic HAp, all HAp:RE3+ powders exhibited paramagnetic behavior. Cell viability tests of HAp:Gd/Yb/Tm and HAp:Gd/Eu powders in human dental pulp stem cell cultures indicated their good biocompatibility.

The biocompatibility of silver and nanohydroxyapatite coatings on titanium dental implants with human primary osteoblast cells.

Silver nanoparticles (Ag NPs) are antimicrobial, with potential uses in medical implants, but Ag NPs alone can also be toxic to mammalian cells. This study aimed to enhance the biocompatibility of Ag NP-coated titanium dental implants with hydroxyapatite (HA) applied to the surface. Ti6Al4V discs were coated with Ag NPs, Ag NPs plus HA nanoparticles (Ag + nHA), or Ag NPs plus HA microparticles (Ag + mHA). The stability of coatings was explored and the biocompatibility with primary human osteoblasts over 7 days. Results showed that Ti6Al4V discs were successfully coated with silver and HA. The primary particle size of nHA and mHA were 23.90 ± 1.49 nm and 4.72 ± 0.38 μm respectively. Metal analysis showed that underlying silver coatings remain stable in DMEM culture media, but the presence of FBS in the media caused some initial (clinically beneficial) release of dissolved silver. With additions of HA, osteoblasts were adherent, had normal morphology, negligible lactate dehydrogenase (LDH) leak, and showed alkaline phosphatase (ALP) activity. Cell viability was around 70% throughout the Ag + nHA treatment. Overall, the implants coated with Ag + nHA maintained a higher degree of biocompatibility compared to those coated with Ag + mHA, or Ag NPs alone, suggesting the former has a benefit for clinical use.