Construction of a stereocomplex between poly(D-lactide) grafted hydroxyapatite and poly(L-lactide): toward a bioactive composite scaffold with enhanced interfacial bonding.

The poly(L-lactide) (PLLA)/hydroxyapatite (HAP) composite scaffold is expected to combine the favorable compatibility and processability of PLLA with the excellent bioactivity and osteoconductivity of HAP. Unfortunately, the poor interfacial bonding between PLLA and HAP leads to a deterioration in mechanical properties. In this study, poly(D-lactide) (PDLA) was grafted onto the surface of HAP nanoparticles (g-HAP), and then g-HAP was incorporated into PLLA to improve interfacial bonding by stereocomplexation in a scaffold fabricated via selective laser sintering (SLS). The results showed that HAP nanoparticles were grafted with PDLA at a grafting rate of 8.72% by ring-opening polymerization through chemical bonding in the presence of the hydroxyl groups of HAP. The grafted PDLA formed an interfacial stereocomplex with PLLA via an intertwined spiral structure ascribed to their antiparallel and complementary configuration under the action of hydrogen bonding. Consequently, the tensile strength and modulus of the PLLA/g-HAP scaffold increased by 86% and 69%, respectively, compared to those of the PLLA/HAP scaffold. In addition, the scaffold displayed good bioactivity by inducing apatite nucleation and deposition and possessed good cytocompatibility for cell adhesion, growth and proliferation.

Apatite matrix substituted with biologically essential rare earth elements as an artificial hard tissue substitute: Systematic physicochemical and biological evaluation.

Hydroxyapatite (HAP) forms the main inorganic component of natural bone and hence has been widely use in implant applications. Ionic substitutions in apatite also gains enormous interest during the recent years due to the crucial role played by these elements in the biological process. In this context, the least investigated elements namely lanthanum (La3+ ) and praseodymium (Pr3+ ) have been selected as a potential substitutions in apatite. The results from the analytical techniques confirm the phase purity of the HAP and its ability holds the substitutions at its lattice. Morphological analysis unveils the presence of agglomerated spheroids notwithstanding the ion concentration of substituents. EDX spectra affirm the presence of La and Pr alongside the determined Ca/P atomic ratio of 1.67. La3+ and Pr3+ presence envisaged the good antibacterial efficiency against the tested microbes and further demonstrated the biocompatibility nature from the cytotoxicity analysis.

Seaweed Porphyra yezoensis polysaccharides with different molecular weights inhibit hydroxyapatite damage and osteoblast differentiation of A7R5 cells.

Vascular calcification (VC) is a common pathological manifestation in patients with cardiovascular diseases, leading to high mortality in patients with chronic kidney diseases. The deposition of hydroxyapatite (HAP) crystals on vascular smooth muscle cells leads to cell damage, which promotes osteogenic transformation. In this study, four different molecular weights (MWs ) of Porphyra yezoensis polysaccharides (PYP1, PYP2, PYP3, and PYP4 with MWs of 576, 49.5, 12.6, and 4.02 kDa, respectively) were used to coat HAP, and the differences in toxicity and calcification of HAP on A7R5 cells before and after coating were studied. The results showed that PYPs could effectively reduce HAP damage to the A7R5 cells. Under the protection of PYPs, cell viability increased and lactate dehydrogenase release, active oxygen level, and cell necrosis rate decreased; also, the amount of the HAP crystals adhering to cell surfaces and entering cells decreased. PYPs with low molecular weights presented better protective effects than high-molecular-weight PYPs. PYPs also inhibited the osteogenic transformation of the A7R5 cells induced by HAP and decreased alkaline phosphatase (ALP) activity and expressions of bone/chondrocyte phenotype genes (runt-related factor 2, ALP, osteopontin, and osteocalcin). In the adenine-induced chronic renal failure (CRF) mouse VC model, PYP4 was found to obviously inhibit the aortic calcium level, and it also inhibited the serum creatinine, serum phosphorus and serum BUN levels. PYP4 (least molecular weight) showed the best inhibitory effect on calcification and may be considered as a candidate drug with therapeutic potential for inhibiting cellular damage and osteoblast differentiation induced by the HAP crystals.

Demineralized bone matrix paste formulated with biomimetic PLGA microcarriers for the vancomycin hydrochloride controlled delivery: Release profile, citotoxicity and efficacy against S. aureus.

Infection and resulting bone defects caused by Staphylococcus aureus is one of the major issues in orthopaedic surgeries. Vancomycin hydrochloride (VaH) is largely used to manage these events. Here, a human derived bone paste supplemented with biopolymer microcarriers for VaH sustained delivery to merge osteoinductive and antimicrobial actions is described. In detail, different emulsion formulations were tested to fabricate micro-carriers of poly-lactic-co-glycolic acid (PLGA) and hydroxyapatite (HA) by a proprietary technology (named Supercritical Emulsion Extraction). These carriers (mean size 827 ± 68 µm; loading 47 mgVaH/gPLGA) were assembled with human demineralized bone matrix (DBM) to obtain an antimicrobial bone paste system (250 mg/0.5 cm3 w/v, carrier/DBM). Release profiles in PBS indicated a daily drug average release of about 4 µg/mL over two weeks. This concentration was close to the minimum inhibitory concentration and able to effectively inhibit the S. aureus growth in our experimental sets. Carriers cytotoxicity tests showed absence of adverse effects on cell viability at the concentrations used for paste assembly. This approach points toward the potential of the DBM-carrier-antibiotic system in hampering the bacterial growth with accurately controlled antibiotic release and opens perspectives on functional bone paste with PLGA carriers for the controlled release of bioactive molecules.

Utility and safety of commercially available injection laryngoplasty materials in a rabbit model.

OBJECTIVE: To demonstrate foreign body and chronic inflammatory reaction of commercially available injection materials using the rabbit vocal fold paralysis model. STUDY DESIGN: Animal study. METHODS: The left recurrent laryngeal nerve was identified and divided at the tracheoesophageal groove. Amounts (100 µL) of phosphate-buffered saline (PBS), polyacrylamide hydrogel (Aquamid; Ferrosan A/S, Søborg, Denmark), calcium hydroxyapatite (Radiesse; BioForm Medical Inc., San Mateo, CA), or hyaluronic acid derivative (Rofilan; Rofil Medical International, Breda, Netherlands) were injected into the left vocalis muscle. Six months later, the larynx was harvested. Hematoxylin/eosin and Masson trichrome staining were performed to compare inflammatory and foreign body reactions, granuloma development, and relative vocal fold areas among groups. RESULTS: Compared with the PBS (control) group, the Aquamid, Radiesse, and Rofilan groups exhibited only mild chronic inflammatory reactions that did not significantly differ among groups, or from controls (P > 0.05). However, the Aquamid and Radiesse groups exhibited moderate foreign body reactions that were significantly greater than those of controls (P < 0.05). No foreign body granuloma formed in any group. All test groups exhibited significant increases in vocal fold areas at 6 months (P < 0.05). CONCLUSIONS: Although commercially available injection materials induced more foreign body reactions than a control injection of PBS, no foreign body granuloma developed and the augmented vocal fold area was maintained until 6 months after injection.

Lowering the dose of sirolimus, released from a nonpolymeric hydroxyapatite coated coronary stent, reduces signs of delayed healing.

OBJECTIVES: The aim of this study was to compare efficacy of low- and high-dose sirolimus release (25, 40, or 100 microg) from hydroxyapatite (HAp) with Cypher (Cordis, Johnson & Johnson, Warren, New Jersey) (111 microg sirolimus) in porcine coronary arteries. BACKGROUND: Polymer-based sirolimus-eluting stents such as Cypher interfere with vascular healing, probably due to the permanent presence of the polymer coating and the high sirolimus dose. The use of low-dose sirolimus and inert nonpolymeric but biodegradable coatings such as HAp might be more appropriate. METHODS: Stents (n = 68) were implanted, guided by quantitative coronary angiography. All swine received clopidogrel and acetylsalicylic acid during 28 days follow-up. Safety of the coating in absence of drugs was studied by comparing HAp with and without a lipid-based release regulating layer (HApR) with bare-metal stents. Efficacy was studied by comparing the release of 25, 40, and 100 microg sirolimus with Cypher. RESULTS: The safety study (without drug) revealed no differences in neointimal thickening in response to HAp and HApR with complete healing in all groups. Dose response analysis showed that neointimal thickening was similar in all groups regardless of sirolimus dose, with a normal appearance of the endothelium. There was, however, a dose-dependent increase in fibrinoid (p = 0.028), considered to be a marker of delayed healing. The Cypher stent induced the highest amount of fibrinoid. CONCLUSIONS: Reducing the dose of sirolimus eluting from a biocompatible HAp coated stent reduces signs of delayed vascular healing, without affecting neointimal hyperplasia.

Improvement in biocompatibility of ZrO2-Al2O3 nano-composite by addition of HA.

The biocompatibility of zirconia-alumina (ZA) nano-composites in load-bearing applications such as dental/orthopedic implants was significantly enhanced by the addition of bioactive HA. The ZA matrix was composed of nano-composite powder obtained from the Pechini process and had higher flexural strength than conventionally mixed zirconia-alumina composite. Because the ZA nano-composite powder effectively decreased the contact area between HA and zirconia for their reaction during the sintering process, the HA-added ZA nano-composites contained biphasic calcium phosphates (BCP) of HA/TCP and had higher flexural strength than conventionally mixed ZA-HA composite. From the in vitro test with osteoblastic cell-lines, the proliferation and the differentiation (as expressed by the alkaline phosphatase activity) of the cellular response on the HA-added ZA nano-composites gradually increased as the amount of HA added increased. From the mechanical and biological evaluations of the HA-added ZA nano-composites, 30HA (30 vol% HA + 70 vol% ZA) was found to be the optimal composition for load-bearing biological applications.

[New ceramic materials for use in anophthalmia surgery]. / Neue Keramikmaterialien zur Verwendung in der Anophthalmuschirurgie.

Over the last 20 years eyeball replacement surgery has improved, especially with the widely accepted use of biocolonisable implants. These implants allow long-lasting biointegration, thus improving prosthesis motility and reducing the rate of postoperative exposure. In this article, we review the chemical structure, toxicity data and manufacturing procedures of the three main commercially available materials: aluminium, hydroxyapatite and porous polyethylene.

Surface and biological evaluation of hydroxyapatite-based coatings on titanium deposited by different techniques.

Hydroxyapatite coatings have been deposited on titanium cp by plasma spray, sol-gel, and sputtering techniques for dental implant applications. The latter two techniques are of current interest, as they allow coatings of micrometer dimensions to be deposited. Coating morphology, composition, and structure have been investigated by scanning electron microscopy (SEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). All coatings were homogeneous and exhibited a rough morphology suitable for implant applications. The sputtered (after annealing), plasma spray, and sol-gel coatings all showed diffraction peaks corresponding to hydroxyapatite. The surface contaminants were observed to be different for the different coating types. The sputtered coatings were found to have a composition most similar to hydroxyapatite; the sol-gel deposits also showed a high concentration of hydroxyl ions. A discrepancy in the Ca/P ratio was observed for the plasma spray coatings, and a small concentration of carbonate ions was found in the sputter-deposited coatings. The in vitro cell-culture studies using MG63 osteoblast-like cells demonstrated the ability of cells to proliferate on the materials tested. The sol-gel coating promotes higher cell growth, greater alkaline phosphatase activity, and greater osteocalcin production compared to the sputtered and plasma-sprayed coatings.

Effect of hydroxyapatite sintering temperature on intracellular ionic concentrations of monocytes: a TEM-cryo-X-ray microanalysis study.

Hydroxyapatite used as bone replacement can lead to particle release in the implantation site. These particles interact with monocytes, which are the first immune cells to colonize the implant and an inflammatory site. Thanks to cryo-X-ray microanalysis, we can observe cells in a state close to the physiological one and we have access to diffusible ions. We paid particular attention to the potassium-to-sodium ratio, which is one of the best viability criteria. We used this method to study the interaction between three hydroxyapatite particles treated at three different temperatures (not treated, treated at 600 degrees C and 1180 degrees C), and monocytes. In the culture condition, the hydroxyapatite treated at 1180 degrees C underwent the least dissolution. We demonstrate that monocytes were altered by the three hydroxyapatite particles. The hydroxyapatite particules treated at 600 degrees C were found to be more toxic.

Subcutaneous inflammatory reaction to a synthetic auditory ossicle (Bioceram) in rats.

Cellular response and inflammatory reaction to synthetic auditory ossicle (Bioceram) made from aluminium oxide are investigated. Local inflammatory effects are important in wound healing and in determining biocompatibility of an implant, necessitating the study of biologic effects of implants, especially inflammation and fibrous capsule formation. Bioceram discs were implanted subcutaneously in the interscapular region of rats for various periods of time, ranging from 1 day to 300 days. Histological sections 6 microns thick were stained with haematoxylin and eosin. Cell types around the implants were examined quantitatively by light microscopy. Inflammatory cell reaction to Bioceram decreased rapidly within 14 days, similar to the reaction in control groups. From 30 days to 300 days after implantation, there was continuous reduction to very low levels for macrophages and lymphocytes, but fibrous connective tissue capsule around implants matured. Preliminary results suggest that Bioceram is a satisfactory biocompatible material for reconstructive surgery from the viewpoint of cellular response. We also briefly discuss the different tissue responses in light of our previous study on hydroxyapatite (Apaceram).