Low temperature formation of calcium-deficient hydroxyapatite-PLA/PLGA composites

Hydroxyapatite-biodegradable polymer composites have been formed by a low temperature chemical route. Precomposite structures were prepared by combining alpha-Ca(3)(PO(4))(2) (alpha-tricalcium phosphate or alpha-TCP) with poly(L-lactic) acid and poly(DL-lactide-co-glycolide) copolymers. The final composite structure was achieved by in situ hydrolysis of alpha-TCP to Ca(9)(HPO(4))(PO(4))(5)OH (calcium deficient hydroxyapatite or CDHAp) either in solvent cast or pressed precomposites. Hydrolysis was performed at 56 degrees C-a temperature slightly above the glass transition of the polymers. The effects of polymer chemistry, composite formation technique, and porosity on hydrolysis kinetics and degree of transformation were examined with isothermal calorimetry, X-ray diffraction (XRD), Fourier transform infrared spectroscopy, and scanning electron microscopy. Calorimetric data and XRD analyses revealed that hydrolysis reactions were inhibited in the presence of the polymers. Isothermal calorimetry indicated the extent of the alpha-TCP to CDHAp transformation in 24 h to be 85% in the solvent cast composites containing PLGA (85:15) copolymer; however, XRD analyses suggested almost complete reaction. The CDHAp formation extent was 26% for the pressed composites containing the same polymer. In the presence of NaCl as a pore generator, 81% transformation was observed for the pressed composites. This transformation occurred without any chemical reaction between the polymer-inorganic components, as determined by Fourier transform infrared spectroscopy. Minimal transformation to CDHAp occurred in composites containing poly(L-lactic) acid.     

Binary CaO-SiO(2) gel-glasses for biomedical applications

Bioactive materials are routinely used in dental and orthopaedic applications. The concept was first introduced in 1971, with the discovery of 45S5 Bioglass, which is known to develop an interfacial bond between the implant and the host tissue. This glass is composed of SiO(2), CaO, P(2)O(5) and Na(2)O. Since then numerous glasses and glass ceramics with similar compositions have been extensively studied for clinical applications. Until 1990 it was accepted that P(2)O(5) and Na(2)O were necessary components for the glass composition to be bioactive. However, calcium silicate glasses with high SiO(2) content are impossible to produce using the traditional melt-quench method. This is due to the liquid-liquid immiscibility region that is present between 0.02 and 0.3 mole fraction of CaO and in terms of bioactivity, high CaO compositions were inferior to those quaternary bioactive glass compositions already in existence. In the last few years several studies have been reported regarding the production of CaO-SiO(2) glasses via the sol-gel processing technique. This report summarises the findings of the past and the present and also outlines potential of these calcium silicate gel-glasses in the field of biomaterials.     

New PMMA-co-EHA glass-filled composites for biomedical applications: Mechanical properties and bioactivity

A bioactive glass of the 3CaO.P(2)O(5)-MgO-SiO(2) system was incorporated as a filler into poly(methylmethacrylate)-co-(ethylhexylacrylate) (PMMA-co-EHA) copolymer. The effect of filler proportion (0, 30, 40 and 50wt.%) on the bending properties was evaluated and a maximum flexural strength of 29MPa coupled with an elastic modulus of 1.1GPa was obtained at an intermediate filler concentration (30wt.%). These values are slightly higher than those usually reported for human cancellous bone. The in vitro bioactivity was assessed by determining the changes in surface morphology and composition after soaking in simulated body fluid (SBF, Kokubo solution). Inductively coupled plasma was used to trace the evolution of ionic concentrations in the SBF solution, namely Ca and P. X-ray diffraction and scanning electron microscopy confirmed the growth of spherical calcium phosphate aggregates on the surface of composites, indicating that the composites are potentially bioactive.     

Low density biodegradable shape memory polyurethane foams for embolic biomedical applications

Low density shape memory polymer foams hold significant interest in the biomaterials community for their potential use in minimally invasive embolic biomedical applications. The unique shape memory behavior of these foams allows them to be compressed to a miniaturized form, which can be delivered to an anatomical site via a transcatheter process and thereafter actuated to embolize the desired area. Previous work in this field has described the use of a highly covalently crosslinked polymer structure for maintaining excellent mechanical and shape memory properties at the application-specific ultralow densities. This work is aimed at further expanding the utility of these biomaterials, as implantable low density shape memory polymer foams, by introducing controlled biodegradability. A highly covalently crosslinked network structure was maintained by use of low molecular weight, symmetrical and polyfunctional hydroxyl monomers such as polycaprolactone triol (PCL-t, Mn = 900 g), N,N,N0,N0-tetrakis(hydroxypropyl)ethylenediamine and tris(2-hydroxyethyl)amine. Control over the degradation rate of the materials was achieved by changing the concentration of the degradable PCL-t monomer and by varying the material hydrophobicity. These porous SMP materials exhibit a uniform cell morphology and excellent shape recovery, along with controllable actuation temperature and degradation rate. We believe that they form a new class of low density biodegradable SMP scaffolds that can potentially be used as “smart” non-permanent implants in multiple minimally invasive biomedical applications.     

Pectin/poly(lactide-co-glycolide) composite matrices for biomedical applications

The aim of the research was to develop matrices for the delivery of biologically active substances for tissue regeneration. To this end, a new biodegradable matrix composed of a hydrophobic porous poly(lactide-co-glycolide), p(LGA), network entangled with another network of hydrophilic pectin was fabricated in the presence of calcium chloride. The calcium salts function as both a pore forming reagent and cross-linker for the formation of pectin networks; the method combines creating pores and cross-linking polymers in one step. Microscopic imaging and dynamic mechanical analysis revealed a double-network structure of the composite matrices. The pectin enables the composite to carry signal molecules. This is accomplished by linking signal molecules to pectin by physical adsorption or by chemical reaction. The p(LGA) networks in the composite impart mechanical properties comparable to p(LGA) alone. The mechanical properties of the composite are far superior to matrices containing only pectin. Furthermore, the pectin-containing matrices improved cell adhesion and proliferation when compared to plain p(LGA) matrices, as determined in vitro by osteoblast culture.     

High temperature behavior of poly[bis(2,2,2-trifluoroethoxy)phosphazene]

Mesomorphic features of poly[bis(2,2,2-trifluoroethoxy)phosphazene] (PBFP) with high (≈10⁷) and low (≈10⁴) molecular weights have been investigated by X-ray diffraction techniques, differential scanning calorimetry optical and electron microscopy, and small-angle X-ray scattering. Characterization measurements were made from room temperature to ≈300°C, which is well above T_m, the designated melting temperature of PBFP. The wide angle X-ray scattering (WAXS) may be interpreted in support of some kind of “nano-scale order” persisting above the isotropization temperature, T_m, of this polymer. There is other evidence to the contrary, namely the optical isotropicity between crossed-polars (depicts melting) and the absence of discrete small angle X-ray scattering (SAXS) under these same conditions. An attempt is made here to establish if these features above T_m are related to molecular weight.     

Elastomers for biomedical applications

Current topics in elastomers for biomedical applications are reviewed. Elastomeric biomaterials, such as silicones, thermoplastic elastomers, polyolefin and polydiene elastomers, poly(vinyl chloride), natural rubber, heparinized polymers, hydrogels, polypeptides elastomers and others are described. In addition biomedical applications, such as cardiovascular devices, prosthetic devices, general medical care products, transdermal therapeutic systems, orthodontics, and ophthalmology are reviewed as well. Elastomers will find increasing use in medical products, offering biocompatibility, durability, design flexibility, and favorable performance/ cost ratios. Elastomers will play a key role in medical technology of the future.     

HDPE-Al2O3-HAp composites for biomedical applications: processing and characterizations

The objective of this work is to demonstrate how the stiffness, hardness, as well as the biocompatibility property, of bioinert high-density polyethylene (HDPE) can be significantly improved by the combined addition of both bioinert and bioactive ceramic fillers. For this purpose, different volume fractions of hydroxyapatite and alumina, limited to a total of 40 vol %, have been incorporated in HDPE matrix. All the hybrid composites and monolithic HDPE were developed under optimized hot pressing condition (130 degrees C, 0.5 h, 92 MPa pressure). The results of the mechanical property characterization reveal that higher elastic modulus (6.2 GPa) and improved hardness (226.5 MPa) could be obtained in the developed HDPE-20 vol %-HAp-20 vol % Al(2)O(3) composite. Under the selected fretting conditions against various counterbody materials (steel, Al(2)O(3), and ZrO(2)), an extremely low COF of (0.07-0.11) and higher wear resistance (order of 10(-6) mm(3)/Nm) are obtained with the HDPE/20 vol % HAp/20 vol % Al(2)O(3) composite in both air and simulated body fluid environment. Importantly, in-vitro cell culture study using L929 fibroblast cells confirms favorable cell adhesion properties in the developed hybrid composite.     

Transparent micro- and nanopatterned poly(lactic acid) for biomedical applications

The formation of structures in poly(lactic acid) has been investigated with respect to producing areas of regular, superficial features with dimensions comparable to those of cells or biological macromolecules. Nanoembossing, a novel method of pattern replication in polymers, has been used for the production of features ranging from tens of micrometers, covering areas up to 1 cm(2), down to hundreds of nanometers. Both micro- and nanostructures are faithfully replicated. Contact-angle measurements suggest that positive microstructuring of the polymer (where features protrude from the polymer surface) produces a more hydrophilic surface than negative microstructuring. The ability to structure the surface of the poly(lactic acid), allied to the polymer's postprocessing transparency and proven biocompatibility, means that thin films produced in this way will be useful for bioengineers studying the interaction of micro- and nanodimensioned features with biological specimen, with regard to tissue engineering, for example.     

Effect of CaF2 on densification and properties of hydroxyapatite-zirconia composites for biomedical applications

Hydroxyapatite (HA) composites with zirconia (ZrO2) up to 40 vol% were fabricated with the addition of CaF2. The sinterability of the composites was found to be enhanced markedly by the addition of small amounts of CaF2 (< 5 vol%). Decomposition of HA to beta-TCP was suppressed due to the substitution of F- for OH-, consequently forming fluor-hydroxyapatite (FHA) solid solution. This suppression of decomposition allowed the production of a fully dense body, which retained both high flexural strength and fracture toughness. The osteoblast-like cell (MG63) response to these F- ion-containing composites displayed comparable cell viability to pure-HA by in vitro proliferation test.     

Process development of an acellular dermal matrix (ADM) for biomedical applications

The object of this study was to compare the extent of decellularization at each critical step of processing porcine skin to produce an acellular dermal matrix (ADM) for biomedical applications. The results demonstrated that the removal of epidermis using treatment with 0.25% trypsin for 18 h and 0.1% sodium dodecyl sulfate (SDS) for 12 h at room temperature was beneficial for the subsequent treatment to remove cells in the dermal structure. Lengthy incubation in 0.25% trypsin (12 h) and then 560 units/l Dispase (12 h) at 25 degrees C of small pieces of porcine skin from which the epidermis had been removed efficiently removed cells and cellular components from the skin. Histological examinations revealed that the epidermis, dermal fibroblasts, and epidermal appendages were completely removed by these treatments, and the basic dermal architecture of collagen bundles was that of a loose meshwork. Examinations by TEM showed that the characteristics of collagen fibers in the ADM were retained after complete removal of cells present under optimal conditions defined in this study. SDS-PAGE and size-exclusion HPLC revealed that collagen fibers in the ADM were mostly type I and showed two typical component peaks identified as oligomers and monomers, respectively.     

Casein and soybean protein-based thermoplastics and composites as alternative biodegradable polymers for biomedical applications

This work reports on the development and characterization of novel meltable polymers and composites based on casein and soybean proteins. The effects of inert (Al(2)O(3)) and bioactive (tricalcium phosphate) ceramic reinforcements over the mechanical performance, water absorption, and bioactivity behavior of the injection-molded thermoplastics were examined. It was possible to obtain materials and composites with a range of mechanical properties, which might allow for their application in the biomedical field. The incorporation of tricalcium phosphate into the soybean thermoplastic decreased its mechanical properties but lead to the nucleation of a bioactive calcium-phosphate film on their surface when immersed in a simulated body fluid solution. When compounded with 1% of a zirconate coupling agent, the nucleation and growth of the bioactive films on the surface of the referred to composites was accelerated. The materials degradation was studied for ageing periods up to 60 days in an isotonic saline solution. Both water uptake and weight loss were monitored as a function of the immersion time. After 1 month of immersion, the materials showed signal of chemical degradation, presenting weight losses up to 30%. However, further improvement on the mechanical performance and the enhancement of the hydrolytic stability of those materials will be highly necessary for applications in the biomedical field.     

Generation of porous microcellular 85/15 poly (DL-lactide-co-glycolide) foams for biomedical applications

Porous 85/15 poly (DL-lactide-co-glycolide) or PLGA foams were produced by the pressure quench method using supercritical CO2 as the blowing agent. The rate of CO2 uptake and CO2 equilibrium concentration in PLGA at different processing conditions were studied by performing sorption experiments. The effects of saturation pressure and temperature on average cell size and relative density of the resulting foams were also studied. The time required to approach equilibrium exhibited a minimum with increasing saturation pressure. The diffusion coefficient and equilibrium concentration of CO2 in PLGA increased with an increasing pressure in an approximately linear relationship. Porous PLGA foams were generated with relative densities ranging from 0.107 to 0.232. Foams showed evidence of interconnected cells with porosities as high as 89%. The pore size ranged from 30 to 100 microm.     

Dielectric properties of poly[bis(trifluoroethoxy)phosphazene] and poly[bis(m-methylphenoxy)phosphazene]

Dielectric properties of poly[bis(trifluoroethoxy)phosphazene] (PFEP) and poly[bis(m-methylphenoxy)phosphazene] (PmMPP) were studied in a temperature range from ?195 to 120°C and at several frequencies between 0,1 and 100 kHz. In PFEP, two relaxations, an α relaxation above the glass transition temperature (T_g) and a β relaxation below T_g, which are related to a glass-rubber transition and a local molecular motion of short segments, respectively, were observed. However, PmMPP shows no β relaxation. From the above dielectric results, it was concluded that side groups play an important role in molecular motion of the polyphosphazenes. In PmMPP a γ′ relaxation was found below T_g by immersing the polymers into water. The γ′ relaxation is related to the molecular motin of absorbed water.     

Long-term strength of ceramics for biomedical applications

The influence of slow crack growth on the initiation of radial cracks at the lower surfaces of ceramic layers bonded to polymeric substrates is studied, with particular relevance to biomechanical systems, e.g., dental crowns and hip replacement prostheses. Critical loads are measured as a function of loading rate (dynamic fatigue) for model bilayers fabricated by epoxy-bonding selected clinical ceramics to polycarbonate bases. Radial crack initiation is observed in situ by viewing from below the transparent base during loading. Declines in the critical loads with diminishing load rate are consistent with slow crack growth of intrinsic flaws prior to radial crack pop in. A simple fracture mechanics relation incorporating a crack velocity function is used to analyze the data. Extrapolation beyond the data range enables long-lifetime (10 yr) estimates of sustainable loads. The procedure provides a basis for ranking ceramic types, and in particular for eliminating vulnerable candidate materials, for use in biomechanical systems. While slow crack growth is an important factor in failure, other mechanisms could operate in concert and even dominate under severe testing conditions, especially under cyclic loading.     

Novel cholic acid functionalized star oligo/poly(DL-lactide)s for biomedical applications

Novel cholic acid functionalized star oligo/poly(DL-lactide)s with different molecular weights were synthesized through the ring-opening polymerization of DL-lactide initiated by cholic acid. Compared with poly(DL-lactide), these star oligo/poly(DL-lactide)s show faster hydrolytic degradation rates, and the degradation mechanism changes from bulk erosion to surface erosion with decreasing molecular weight. Based on the specific physicochemical properties of the novel star oligo/poly(DL-lactide), the drug delivery system with submicron size was fabricated using a very convenient "ultrasonic dispersion method" which did not involve toxic organic solvents. The in vitro drug release was studied.     

Porosity effects of natural latex (Hevea brasiliensis) on release of compounds for biomedical applications

Natural rubber latex biomedical (NRLb) obtained from the rubber tree Hevea brasiliensis has shown great potential in biomedicine and biomaterial applications. NRLb has been utilized as a physical barrier against infectious agents and in the controlled release of drugs and extracts. In the present work, NRLb was polymerized in a lyophilizer using different volumes of water to control the resultant membrane porosity and characterized regarding the surface morphology, water vapour permeability (WVP), mechanical properties, haemolytic activity and cytotoxicity. The release of bovine serum albumin protein from the latex membranes was evaluated. Drug release rates increased with porosity and membranes were able to control protein release up to 12 h. In addition, WVP increased with the quantity of pores. The cell viability observed for the porous membrane was higher than that noted for conventional membranes. In summary, the porosity control of natural latex membranes can be used to modulate properties and make them suitable for biomedical applications, such as wound dressings, modulated gas-exchange membranes and controlled drug delivery systems.     

Initial interaction of osteoblasts with the surface of a hydroxyapatite-poly(methylmethacrylate) cement

Failure of the bone/cement interface in cemented joint prostheses is a contributor to implant loosening. The introduction of a bioactive phase, such as hydroxyapatite (HA), to cement may enhance fixation by encouraging direct bone apposition rather than encapsulation of the implant by fibrous tissue. The effect of poly(methylmethacrylate) (PMMA) bone cement (incorporating 17.5% HA wt.) on bioactivity has been investigated using primary human osteoblast-like cells (HOB). A significantly higher cell proliferation and differentiation was seen on the PMMA/HA cement compared to the PMMA cement alone, with retention of phenotype up to 21 days of culture on both materials.