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The conventional approaches for treating bone defects such as autografts donor tissue shortages and allografts transmission of diseases pose many shortcomings. The objective of this study was to design a nano strontium/magnesium doped hydroxyapatite (Sr/Mg-HA) with chitosan (CTS) and multi-walled carbon nanotubes (MWCNT) (Sr/Mg-HA/MWCNT/CTS) biocomposite was created to support the growth of osteoblasts using a solvent evaporation method. To help the growth of osteoblasts, a solvent evaporation technique was used to design a nano strontium/magnesium doped hydroxyapatite with chitosan and multi-walled carbon nanotubes biocomposite. We studied the biocompatibility and efficiency in vitro of biocomposite following physicochemical analyzes. Tests of biocompatibility, cell proliferation, mineralization, and osteogenic differentiation have shown that in-vitro safety and effectiveness of biocomposite are good. The performance of biocomposite was more efficient in in-vitro as well as in vivo experiments than in Sr/Mg-HA nanoparticles. Briefly, the Sr/Mg-HA/MWCNT/CTS biocomposite is an ideal candidate for effective bone repair in clinics with excellent mechanical properties with durable multi-biofunctional antibacterial properties and osteoinductivity.

Type I collagen and nanocrystalline-substituted hydroxyapatite are the major components of a natural composite—bone tissue. Both of these materials also play a significant role in orthopedic surgery and implantology; however, their separate uses are limited; apatite is quite fragile, while collagen’s mechanical strength is very poor. Therefore, in biomaterial engineering, a combination of collagen and hydroxyapatite is used, which provides good mechanical properties with high biocompatibility and osteoinduction. In addition, the porous structure of the composites enables their use not only as bone defect fillers, but also as a drug release system providing controlled release of drugs directly to the bone. This feature makes biomimetic collagen–apatite composites a subject of research in many scientific centers. The review focuses on summarizing studies on biological activity, tested in vitro and in vivo.

There is an increased interest in developing biocomposite implants with high biocompatibility in order to be used as grafts or prostheses in orthopedic surgery. The purpose of the study was to determine the biocompatibility of titanium implants coated with synthesized hydroxyapatite-alendronate composites. The implants were obtained using Matrix Assisted Pulsed Laser Evaporation technique (MAPLE). The hydroxyapatite-alendronate composites were synthesized using the wet precipitation method. Immunofluorescence microscopy showed that composites support mesenchymal stem cells (MSCs) adhesion. Bone cells as well as human MSCs adhere to hydroxyapatite (HA)-based thin films obtained by matrix assisted laser deposition onto titanium. Alendronate doping into the films increased the number of cell-biomaterial focal points as compared to HA only. Thus, the synthesis of hydroxyapatite-alendronate composite (HA-AL) may be considered a viable solution for including the bisphosphonate on the surface of metallic prosthetic components used in orthopedics.

Kalça veya diz protezi gibi yük taşıma uygulamalarında kullanılacak malzemelerin, uygun mekanik özelliklere (kemiğe en yakın) ve yüksek biyokorozyon direncine sahip olması beklenir. Ayrıca, implantın vücuttan reddedilmesinin önlenmesi ve uzun ömürlü kullanım için biyomalzemenin, insan vücudunda herhangi bir alerjik veya iltihabik reaksiyona neden olmaması gerekir, ilave olarak, osseointegrasyon için implantın bitişik kemik ile entegre edilmesi istenir. Bu özellikleri sağlayan en uygun metalik implant malzemeleri Ti ve alaşımlarıdır. Kalsiyum fosfat bazlı biyoseramikler, özellikle HA, restoratif diş ve ortopedik implantlarda, benzersiz kimyasal kompozisyonları ve insan iskelet apatit sistemine benzer kristal yapıları nedeniyle, kemik replasman materyali olarak yaygın şekilde kullanılmaktadır. Ek olarak, HA benzersiz biyoaktif ve osseokondüktif özelliklere sahiptir. Ancak kırılganlığının ve zayıf mekanik özelliklerinin yük taşıma uygulamaları için engellerden biri olduğu iyi bilinmektedir. Buna karşılık, bazı metalik malzemenin, özellikle de titanyumun iyi mekanik özellikleri, yük taşıma uygulamalarına dayanabilmektedir. Öte yandan, biyouyumluluk kalsiyum fosfat esaslı biyoseramiklerle karşılaştırıldığında daha kötüdür. Ek olarak düşük yapışma kuvveti nedeniyle metal implantlar gevşeyebilir veya çevresindeki dokudan ayrılabilir. Biyoaktivite ve uygun mekanik özelliklerin iyi bir kombinasyonu yük taşıma uygulamaları için iyi tıbbi implantların üretilmesinde ümit verici bir yaklaşım olarak görülmektedir. Ti ve HA'nın yüksek mukavemet ve biyoaktif özellikler sağladığı Ti-HA biyokompoziti iyi bir örnektir. Bu çalışmada Ti'a %5-10-15 oranlarında HA ilave ederek toz metalurjisi yöntemiyle kompozit üretilmesi amaçlanmıştır.Anahtar kelimeler: Titanyum, Hidroksiapatit, Biyokompozit, Biyoseramik, Biyouyumluluk, Toz Metalurjisi. Materials to be used in load bearing applications, such as hip or knee prostheses, are expected to have appropriate mechanical properties (closest to the bone) and high biocorrosion resistance. Furthermore, for prevention of rejection of the implant from the body and for prolonged use, the biomaterial should not cause any allergic or inflammatory reaction in the human body. In addition, it is desirable that the implant be integrated with the adjacent bone for osseointegration. The most suitable metallic implant materials providing these properties are Ti and its alloys.Calcium phosphate based bioceramics, especially HA, have been widely used as bone replacement material in restorative dental and orthopedic implants, due to their unique chemical composition and crystal structure that is similar to the human skeletal apatite system. In addition, HA possesses unique bioactive and osseoconductive properties. However, it is well known that its brittleness and weak mechanical properties is one of the obstacles for load-bearing applications. On the other hand, its biocompatibility is worse when compared to that of calcium phosphate based bioceramics. İn addition, metal implants may become loose or even separated from the surrounding tissue due to its low bonding strength.A good combination of the bioactivity and favorable mechanical properties are considered as a promising approach to fabricating good medical implants for load-bearing applications. A good example is the titanium-hydroxyapatite (Ti-HA) biocomposite, where Ti and HA provide the high strength and bioactive properties. In this study, it is aimed to produce composites using powder metallurgy method by adding hydroxyapatite to titanium.Keywords: Titanium, Hydroxyapatite, Biocomposite, Bioceramic, Biocompatibility, Powder Metallurgy. 56

Hydroxyapatite (HAp) has been used extensively in medical applications for repair or replacement of bone tissues in human body system. It is chemically similar to the mineral component of bone and teeth and will form an artificial bone-like structure with the surrounding bone tissue when implanted. However, sintered hydroxyapatite material exhibits relatively poor mechanical properties than natural bone and as such, improvement of mechanical properties are necessary. One of the candidate materials for the reinforcing phase to HAp is zirconia, ZrO 2 . Medical applications of ZrO 2 implants confirmed their satisfactory biocompatibility, although it cannot bond well to bone tissue. In this study, ZrO 2 /HApbiocomposites were fabricated with the objective to improve the strength and toughness of the biomaterial. Commercial CaO-ZrO 2 (CZ) was selected as the reinforced material to the HAp matrix. Small amounts of CaF 2 were added to improve sinterability and the phase stability of these biocomposites. Conventional ceramic processing route was used to prepare ZrO 2 /HAp samples, which involved milling and mixing, compaction and sintering. X-ray diffraction (XRD), linear shrinkages, density and porosity, flexural strength, Vickers microhardness, toughness, and scanning electron microscopy (SEM) were used to characterize the (ZrO 2 /HAp) biocomposites. XRD results indicate phase stability of biocomposites to a temperature of 1200 °C. Shrinkage of fired samples were very uniform with increasing temperature, with slightly lower shrinkage in thickness direction. In general, strength of the reinforced ZrO 2 /HAp was successfully increased from 35.70 MPa to 52.88 MPa and the toughness was increased from 0.65 MPa.m 1/2 to 1.33 MPa.m 1/2 as well.

This paper proposes the development of a biomimetic composite based on naturally derived biomaterials. This freeze-dried scaffold contains a microwave-synthesized form of biomimetic hydroxyapatite (HAp), using the interwoven hierarchical structure of eggshell membrane (ESM) as bio-template. The bone regeneration capacity of the scaffold is enhanced with the help of added tricalcium phosphate from bovine Bone ash (BA). With the addition of Gelatin (Gel) and Chitosan (CS) as organic matrix, the obtained composite is characterized by the ability to stimulate the cellular response and might accelerate the bone healing process. Structural characterization of the synthesized HAp (ESM) confirms the presence of both hydroxyapatite and monetite phases, in accordance with the spectroscopy results on the ESM before and after the microwave thermal treatment (the presence of phosphate group). Morphology studies on all individual components and final scaffold, highlight their morphology and porous structure, characteristics that influence the biocompatibility of the scaffold. Porosity, swelling rate and the in vitro cytotoxicity assays performed on amniotic fluid stem cells (AFSC), demonstrate the effective biocompatibility of the obtained materials. The experimental results presented in this paper highlight an original biocomposite scaffold obtained from naturally derived materials, in a nontoxic manner.

Background Polyetheretherketone (PEEK) exhibits stable chemical properties, excellent biocompatibility, and rational mechanical properties that are similar to those of human cortical bone, but the lack of bioactivity impedes its clinical application. Methods In this study, hydroxyapatite (HA) was incorporated into PEEK to fabricate HA/PEEK biocomposite using a compounding and injection-molding technique. The tensile properties of the prepared HA/PEEK composites (HA content from 0 to 40 wt%) were tested to choose an optimal HA content. To evaluate the bioactivity of the composite, the cell attachment, proliferation, spreading and alkaline phosphatase (ALP) activity of MC3T3-E1 cells, and apatite formation after immersion in simulated body fluid (SBF), and osseointegration in a rabbit cranial defect model were investigated. The results were compared to those from ultra-high molecular weight polyethylene (UHMWPE) and pure PEEK. Results By evaluating the tensile properties and elastic moduli of PEEK composite samples/PEEK composites with different HA contents, the 30 wt% HA/PEEK composite was chosen for use in the subsequent tests. The results of the cell tests demonstrated that PEEK composite samples/PEEK composite exhibited better cell attachment, proliferation, spreading, and higher ALP activity than those of UHMWPE and pure PEEK. Apatite islands formed on the HA/PEEK composite after immersion in SBF for 7 days and grew continuously with longer time periods. Animal tests indicated that bone contact and new bone formation around the HA/PEEK composite were more obvious than those around UHMWPE and pure PEEK. Conclusions The HA/PEEK biocomposite created by a compounding and injection-molding technique exhibited enhanced osteogenesis and could be used as a candidate of orthopedic implants.

Nano-carbon reinforced titanium matrix/hydroxyapatite (HA) biocomposites were successfully prepared by spark plasma sintering (SPS). The microstructure, mechanical properties, biocompatibility, and the relationship between microstructure and properties of biocomposites were systematically investigated. Results showed there are some new phases in sintered composites, such as &beta, Ti, TiO3, ZrO2, etc. Moreover, a small amount of Ti17P10, CaTiO3, Ca3(PO4)2 were also detected. The reaction that may occur during the preparation process is suppressed to some extent, which is because that the addition of second phases can prevent the direct contact of titanium with HA and reduce the contact areas. Transmission electron microscope (TEM) analysis proved the existence of elemental diffusion and chemical reactions in sintered composites. Compared with results of composites prepared by hot-pressed sintering before, mechanical properties (microhardness, compressive strength, and shear strength) of 0.5-GNFs composites prepared by SPS were increased by about 2.8, 4.8, and 4.1 times, respectively. The better mechanical properties of 0.5-GNFs composite in nano-carbon reinforced composites are mainly due to the lower degree of agglomeration of tubular carbon nanotubes (CNTs) compared to lamellar graphene nanoflakes (GNFs). Moreover, the strengthening and toughening mechanisms of nano-carbon reinforced titanium alloy/HA biocomposite prepared by spark plasma sintering (SPS) mainly included second phase strengthening, grain refinement strengthening, solution strengthening, graphene extraction, carbon nanotubes bridging, crack tail stripping, etc. In addition, in vitro bioactivity test revealed that the addition of nano-carbon was beneficial to promote the adhesion and proliferation of cells on the surface of titanium alloy/HA composite, because nano-carbon can enhance the formation of mineralized necks in the composites after transplantation, stimulate biomineralization and promote bone regeneration.

Guoqiang Zhou,1–3 Sudan Liu,1 Yanyan Ma,1 Wenshi Xu,1 Wei Meng,1 Xue Lin,1 Wenying Wang,1,3 Shuxiang Wang,1–3 Jinchao Zhang1–3 1College of Chemistry and Environmental Science, 2Key Laboratory of Medicinal Chemistry and Molecular Diagnosis of Ministry of Education, 3Key Laboratory of Chemical Biology of Hebei Province, Hebei University, Baoding, Hebei, People’s Republic of China Abstract: The development of an artificial bone graft which can promote the regeneration of fractures or diseased bones is currently the most challenging aspect in bone tissue engineering. To achieve the purpose of promoting bone proliferation and differentiation, the artificial graft needs have a similar structure and composition of extracellular matrix. One-step electrospinning method of biocomposite nanofibers containing hydroxyapatite (HA) nanoparticles and collagen (Coll) were developed for potential application in bone tissue engineering. Nanocomposite scaffolds of poly(L-lactide) (PLLA), PLLA/HA, PLLA/Coll, and PLLA/Coll/HA were fabricated by electrospinning. The morphology, diameter, elements, hydrophilicity, and biodegradability of the composite scaffolds have been investigated. The biocompatibility of different nanocomposite scaffolds was assessed using mouse osteoblasts MC3T3-E1 in vitro, and the proliferation, differentiation, and mineralization of cells on different nanofibrous scaffolds were investigated. The results showed that PLLA/Coll/HA nanofiber scaffolds enhanced cell adhesion, spreading, proliferation, differentiation, mineralization, and gene expression of osteogenic markers compared to other scaffolds. In addition, the nanofibrous scaffolds maintained a stable composition at the beginning of the degradation period and morphology wastage and weight loss were observed when incubated for up to 80 days in physiological simulated conditions. The PLLA/Coll/HA composite nanofibrous scaffolds could be a potential material for guided bone regeneration. Keywords: nanofibrous scaffolds, hydroxyapatite, electrospinning, tissue engineering, degradation, differentiation

Since the 1970s, various types of ceramic, glass and glass-ceramic materials have been proposed and used to replace damaged bone in many clinical applications. Among them, hydroxyapatite (HA) has been successfully employed thanks to its excellent biocompatibility. On the other hand, the bioactivity of HA and its reactivity with bone can be improved through the addition of proper amounts of bioactive glasses, thus obtaining HA-based composites. Unfortunately, high temperature treatments (1200°C÷1300°C) are usually required in order to sinter these systems, causing the bioactive glass to crystallize into a glass-ceramic and hence inhibiting the bioactivity of the resulting composite. In the present study novel HA-based composites are realized and discussed. The samples can be sintered at a relatively low temperature (800 °C), thanks to the employment of a new glass (BG_Ca) with a reduced tendency to crystallize compared to the widely used 45S5 Bioglass®. The rich glassy phase, which can be preserved during the thermal treatment, has excellent effects in terms of in vitro bioactivity; moreover, compared to composites based on 45S5 Bioglass® having the same HA/glass proportions, the samples based on BG_Ca displayed an earlier response in terms of cell proliferation.

© 2016 Trans Tech Publications, Switzerland. Drug delivery systems were developed from coralline hydroxyapatite (HAp) and biodegradable polylactic acid (PLA). Gentamicin (GM) was loaded in either directly to PLA (PLAGM) or in HAp microspheres. Drug loaded HAp was used to make thin film composites (PLAHApGM). Dissolution studies were carried out in phosphate buffered saline (PBS). The release profiles suggested that HAp particles improved drug stabilization and availability as well controlled the release rate. The release also displays a steady state release. In vitro studies in human Adipose Derived Stem Cells (hADSCs) showed substantial quantities of cells adhering to hydroxyapatite containing composites. The results suggested that the systems could be tailored to release different clinical active substances for a wide range of biomedical applications.

Silk fibroin has attracted great interest in tissue engineering because of its outstanding biocompatibility, biodegradability and minimal inflammatory reaction. In this study, two kinds of biocomposites based on regenerated silk fibroin are fabricated by electrospinning and post-treatment processes, respectively. Firstly, regenerated silk fibroin/tetramethoxysilane (TMOS) hybrid nanofibers with high hydrophilicity are prepared, which is superior for fibroblast attachment. The electrospinning process causes adjacent fibers to 'weld' at contact points, which can be proved by scanning electron microscope (SEM). The water contact angle of silk/tetramethoxysilane (TMOS) composites shows a sharper decrease than pure regenerated silk fibroin nanofiber, which has a great effect on the early stage of cell attachment behavior. Secondly, a novel tissue engineering scaffold material based on electrospun silk fibroin/nano-hydroxyapatite (nHA) biocomposites is prepared by means of an effective calcium and phosphate (Ca-P) alternate soaking method. nHA is successfully produced on regenerated silk fibroin nanofiber within several min without any pre-treatments. The osteoblastic activities of this novel nanofibrous biocomposites are also investigated by employing osteoblastic-like MC3T3-E1 cell line. The cell functionality such as alkaline phosphatase (ALP) activity is ameliorated on mineralized silk nanofibers. All these results indicate that this silk/nHA biocomposite scaffold material may be a promising biomaterial for bone tissue engineering., Article, Membranes. 1:275-298 (2011)

Risk assessment of cosmetic ingredients represents a regulatory standard requirement in Europe and other regions. An integrated approach was designed to assess the safety of HPC, a particulate composite of hydroxyapatite and protein (gelatin) for use in oral care products, employing a weight-of-evidence assessment and considering specific physico-chemical properties and exposure conditions. An initial evaluation of the constituents suggested that their chemical nature does not represent a particular health hazard per se. Hydroxyapatite is the main component of teeth and bones in mammals; gelatin is used in food and assumed to be safe once a BSE/TSE risk has been excluded. In vitro screening tests were chosen to further evaluate the biocompatibility: Hen’s egg test-chorioallantoic membrane (HET-CAM) to assess irritating effects towards mucous membranes; MTT cytotoxicity test with 3T3 fibroblasts; human corneal epithelial models to investigate inflammatory mediators and cytotoxicity; macrophage assays to measure cytotoxicity, inflammatory mediators and oxidative stress. Together with results from clinical studies, exposure estimates and analyses of kinetic properties, the presented information provides sound evidence to support the safe use of HPC. This is an example of a risk assessment for cosmetic use of small particles without the need for additional animal studies.

In this study, we develop binary polypropylene (PP) composites with hexagonal boron nitride (hBN) nanoplatelets and ternary hybrids reinforced with hBN and nanohydroxyapatite (nHA). Filler hybridization is a sound approach to make novel nanocomposites with useful biological and mechanical properties. Tensile test, osteoblastic cell culture and dimethyl thiazolyl diphenyl tetrazolium (MTT) assay were employed to investigate the mechanical performance, bioactivity and biocompatibility of binary PP/hBN and ternary PP/hBN-nHA composites. The purpose is to prepare biocomposite nanomaterials with good mechanical properties and biocompatibility for replacing conventional polymer composites reinforced with large hydroxyapatite microparticles at a high loading of 40 vol%. Tensile test reveals that the elastic modulus of PP composites increases, while tensile elongation decreases with increasing hBN content. Hybridization of hBN with nHA further enhances elastic modulus of PP. The cell culture and MTT assay show that osteoblastic cells attach and proliferate on binary PP/hBN and ternary PP/hBN-20%nHA nanocomposites.