Studies on biodegradable and crosslinkable poly(castor oil fumarate)/poly(propylene fumarate) composite adhesive as a potential injectable biomaterial.

Biodegradable hydroxyl terminated-poly(castor oil fumarate) (HT-PCF) and poly(propylene fumarate) (HT-PPF) resins were synthesized as an injectable and in situ-cross linkable polyester resins for orthopedic applications. An injectable adhesive formulation containing this resin blend, N-vinyl pyrrolidone (NVP), hydroxy apatite, free radical initiator and accelerator was developed. The Composite adhesives containing the ratio of resin blend and NVP, 2.1:1.5, 2.1:1.2 and 2.1:1.0 set fast with tolerable exothermic temperature as a three dimensionally cross linked toughened material. Crosslink density and mechanical properties of the crosslinked composite increase with increase of NVP. The present crosslinked composite has hydrophilic character and cytocompatibility with L929 fibroblast cells.

Studies on in vitro biostability and blood compatibility of polyurethane potting compound based on aromatic polymeric MDI for extracorporeal devices.

Polyurethane potting compound based on aromatic isocyanurate of polymeric MDI, poly propylene glycol (PPG400) and trimethylol propane (TMP) has significant favourable properties, good pot life and setting characteristics. The cured potting compound of this formulation has appreciable thermal stability and mechanical properties. In vitro biostability of cured potting compound has been found to be excellent without any significant degradation in simulated physiological media and chemical environment. Studies on blood-material interaction and cytotoxicity reveal in vitro blood compatibility and compatibility with cells of this potting compound.

Studies on biodegradation of crosslinked hydroxy terminated-poly(proplyene fumarate) and formation of scaffold for orthopedic applications.

Biodegradation of crosslinked-hydroxy terminated-poly(proplyene fumarate) (X-HTPPF) has been studied in simulated physiological media to assess the formation of porous scaffold structure for bone growth and remodeling in load bearing orthopedic applications. Variation in crosslink density and surface hydrophilicity of X-HTPPF are observed due to non-stoichiometric mass of reacting partners. These variations influence absorption of the medium and biodegradation during aging. Though the initial absorption of medium is relatively higher with the crosslinked polymer (PNVP1) having 63.6% HT-PPF and 36.4% comonomer n-vinyl pyrrolidone (NVP) during the initial period of aging, the weight loss due to subsequent degradation with time is relatively lesser. PNVP1 undergo slow degradation with formation of fibril structure on the surface. The present crosslinked material PNVP1 is a candidate for the load bearing orthopedic applications.

Studies on novel radiopaque methyl methacrylate: glycidyl methacrylate based polymer for biomedical applications.

A new class of radiopaque copolymer using methyl methacrylate (MMA) and glycidyl methacrylate (GMA) monomers was synthesized and characterized. The copolymer was made radiopaque by the epoxide ring opening of GMA using the catalyst o-phenylenediamine and the subsequent covalent attachment of elemental iodine. The copolymer was characterized by Fourier transform infrared (FTIR) spectra, energy dispersive X-ray analysis using environmental scanning electron microscope (EDAX), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). X-ray visibility of the copolymer was checked by X-radiography. Blood compatibility and cytotoxicity of the newly synthesized copolymer were also evaluated. The iodinated copolymer was thermally stable, blood compatible, non-cytotoxic, and highly radiopaque. The presence of bulky iodine group created a new copolymer with modified properties for potential use in biomedical applications.

Injectable biomaterials for minimally invasive orthopedic treatments.

Biodegradable and injectable hydroxy terminated-poly propylene fumarate (HT-PPF) bone cement was developed. The injectable formulation consisting HT-PPF and comonomer, n-vinyl pyrrolidone, calcium phosphate filler, free radical catalyst, accelerator and radiopaque agent sets rapidly to hard mass with low exothermic temperature. The candidate bone cement attains mechanical strength more than the required compressive strength of 5 MPa and compressive modulus 50 MPa. The candidate bone cement resin elicits cell adhesion and cytoplasmic spreading of osteoblast cells. The cured bone cement does not induce intracutaneous irritation and skin sensitization. The candidate bone cement is tissue compatible without eliciting any adverse tissue reactions. The candidate bone cement is osteoconductive and inductive and allow osteointegration and bone remodeling. HT-PPF bone cement is candidate bone cement for minimally invasive radiological procedures for the treatment of bone diseases and spinal compression fractures.

Profilin isoforms in Dictyostelium discoideum.

Eukaryotic cells contain a large number of actin binding proteins of different functions, locations and concentrations. They bind either to monomeric actin (G-actin) or to actin filaments (F-actin) and thus regulate the dynamic rearrangement of the actin cytoskeleton. The Dictyostelium discoideum genome harbors representatives of all G-actin binding proteins including actobindin, twinfilin, and profilin. A phylogenetic analysis of all profilins suggests that two distinguishable groups emerged very early in evolution and comprise either vertebrate and viral profilins or profilins from all other organisms. The newly discovered profilin III isoform in D. discoideum shows all functions that are typical for a profilin. However, the concentration of the third isoform in wild type cells reaches only about 0.5% of total profilin. In a yeast-2-hybrid assay profilin III was found to bind specifically to the proline-rich region of the cytoskeleton-associated vasodilator-stimulated phosphoprotein (VASP). Immunolocalization studies showed similar to VASP the profilin III isoform in filopodia and an enrichment at their tips. Cells lacking the profilin III isoform show defects in cell motility during chemotaxis. The low abundance and the specific interaction with VASP argue against a significant actin sequestering function of the profilin III isoform.

Intrinsically radiopaque polyurethanes with chain extender 4,4'-isopropylidenebis [2-(2,6-diiodophenoxy)ethanol] for biomedical applications.

Radiopaque polyurethanes are used for medical applications as it allows post-operative assessment of the biomaterial devices using X-ray. Inherently, radiopaque polyurethanes based on polytetramethylene glycol (PTMG), polypropylene glycol, 4,4'-methylenebis(phenyl isocyanate), and a new iodinated chain extender 4,4'-isopropylidenebis[2-(2,6-diiodophenoxy)ethanol] with flexible spacers were synthesized and characterized. The iodinated polyurethanes were clear, optically transparent, and had high molecular weights. The polyurethanes also possessed excellent radiopacity and high thermal stability. The biocompatibility of the most promising iodinated polyurethane was evaluated both in vitro (cytotoxicity evaluation by direct contact and MTT assay, using L929 mouse fibroblast cells) and in vivo (toxicology studies in rabbits and subcutaneous implantation in rats). The material was nontoxic and well tolerated by the animals. Thus, these radiopaque and transparent polyurethanes are expected to have potential for various biomedical applications.

Hybrid alginate-polyester bimodal network hydrogel for tissue engineering--Influence of structured water on long-term cellular growth.

The development of biodegradable scaffolds (which promote cell-binding, proliferation, long-term cell viability and required biomechanical stability) for cardiac tissue engineering is a challenge. In this study, biosynthetic amphiphilic hybrid hydrogels were prepared using a graft comacromer of natural polysaccharide alginate and synthetic polyester polypropylene fumarate (PPF). Monomodal network hydrogel (HPAS-NO) and bimodal network hydrogel (HPAS-AA) were prepared. Between the two hydrogels, HPAS-AA hydrogel excels over the HPAS-NO hydrogel. HPAS-AA hydrogel is mechanically more stable in the culture medium and undergoes gradual degradation in vitro in PBS (phosphate buffered saline). HPAS-AA contains nano-porous structure and acquires structured water (non-freezing-bound water) (53.457%) along with free water (11.773%). It absorbs more plasma proteins and prevents platelet adsorption and hemolysis when contacted with blood. HPAS-AA hydrogel is cytocompatible and promote 3D cell growth (≈ 70%) of L929 fibroblast even after 18 days and H9C2 cardiomyoblasts. The enhanced and long-term cellular growth of HPAS-AA hydrogel is attributed to the cell responsive features of structured water. HPAS-AA hydrogel can be a better candidate for cardiac tissue engineering applications.

Multiple gamma radiation sterilization of polyester fibres.

Gamma radiation with a dose of 2.5 Mrad has been found to be suitable to sterilize polyethylene terephthalate (PET) bulk materials intended for biomedical applications. The radiation stability of PET bulk materials and fibre may not however be taken as identical due to the changes in the polymer structure during the processing of bulk materials for fibre. The chemical changes occurring in PET fibres during single and multiple (prolonged) sterilization in air were investigated. It was found that single sterilization (2.5 Mrad) itself affected the PET yarn and fibre. This was exhibited by the increase of crystallinity from 30.5 to 37% in the case of yarn and from 40 to 44% in the case of fibre. The breaking load of the yarn also increased from 441 g to 451 g. These changes were attributed to the degradation of PET in the amorphous region and the recombination of degraded aliphatic segments. Sterilization at higher doses affected the crystalline region which decreased the crystallinity, breaking load and molecular weight. For samples irradiated at 2.5 Mrad, the breaking load increased, though the dispersity increased. This was attributed to cross-linking by recombination. The increase in crystallinity also enhanced the breaking load of the samples. Higher doses of sterilization led to drastic microstructural and macrostructural changes as seen from the molecular weight. It was inferred that the changes in crystallinity and microstructure that occurred during multiple sterilization might affect the biocompatibility of the material.

Ageing of radiation-sterilized polypropylene: changes in semicrystallinity.

Studies on radiation sterilization of isotactic polypropylene intended for biomedical applications were carried out for uncovered and covered samples. The effect of ageing on these samples was studied by determining the changes in relative crystallinity. The semicrystalline nature of the polymer is responsible for the changes in crystallinity. The transitions between short- and long-range order and short- and long-duration stiffness in both covered and uncovered samples, reflected in changes in relative crystallinity, were highly affected by the formation of branches in the backbone of the polymer. The high degree of branching in covered samples resulted in greater long-duration stiffness in the transition between short- and long-duration stiffness. The high degree of branching in covered samples was attributed to the high diffusion of energized oxygen into the polymer matrix compared with uncovered samples. The changes in relative crystallinity were rapid in uncovered samples (70% max; 34% min) but rather slow in covered samples (87% max; 43% min).

Polypropylene fumarate/phloroglucinol triglycidyl methacrylate blend for use as partially biodegradable orthopaedic cement.

Polypropylene fumarate/phloroglucinol triglycidyl methacrylate oligomeric blend-based bone cement was studied. Higher the percentage of phloroglucinol triglycidyl methacrylate, lesser the setting time. An optimum setting time could be arrived with 50:50 blend composition of the two oligomers. Composite cement of 50:50 blend prepared with hydroxyapatite granules of particle size 125 microm binds bovine rib bones. The tensile strength of this adhesive bond was found to be 1.11 kPa. The thermal studies suggest the onset of cross-linking reaction in the cured blend if the blend is heated. The absence of softening endotherm in the cured blend shows the thermosetting-like amorphous nature of blend system, which may restrict the changes in creep properties. The in vitro biodegradation studies reveal possible association of calcium ions with negatively charged units of degrading polymer chain resulting in slow down of degradation. Relatively slow degradation was observed in Ringer's solution. The study reveals the potential use of polypropylene fumarate/phloroglucinol triglycidyl methacrylate as partially degradable polymeric cement for orthopaedic applications.

Studies on the effect of degree of hydrophilicity on tissue response of polyurethane interpenetrating polymer networks.

Interpenetrating polymer networks of polyurethane and vinyl monomers such as polyacrylamide, polyvinyl pyrrolidone, poly(hydroxyethyl methacrylate) and poly(methyl methacrylate) were implanted intramuscularly in rabbits. Attempts were made to correlate the morphological aspects of the interpenetrating polymer networks to their histological response. A relatively increased hydrophilicity of hydrophobicity of the interpenetrating polymer networks as in the case of polyurethane-polyvinyl pyrrolidone and polyurethane-poly(methyl methacrylate) interpenetrating polymer networks, respectively, could elicit an inert response whilst degradation of materials promoted reactivity.

Sterilization and reprocessing of materials and medical devices--reusability.

Problems associated with reprocessing of disposable medical devices such as hemodialysers with resterilization for reuse and changes in material properties with resterilization of polymeric (PVC, polypropylene, polyester, polycarbonate) materials intended for development of disposable devices are reviewed. Reprocessing of hospital supplies, polystyrene microtiter plate and angiographic catheter for reuse is also discussed.

Biological interactions: causes for risks and failures of biomaterials and devices.

Biomaterials and devices have been used in a variety of applications ranging from disposable extracorporeal devices and soft and hard tissue augmentation, to total artificial internal organs. However, there are risks and failures in each application which are a result of undesirable biological interactions. This article deals with various biological interactions in each category of implants and devices used in medical applications.

Studies on polyurethane potting compound based on isocyanurate of aliphatic diisocyanate for fabrication of a haemodialyser.

Polyurethane potting compounds based on multifunctional isocyanurate of aliphatic diisocyanate, hexamethylene diisocyanate (HDI-IC) as Component A and polypropylene glycol, polyethylene glycol and castor oil (Component B) were prepared as potential potting compounds for the fabrication of a haemodialyser. The setting characteristics of the potting compounds having isocyanate index 2.54 are better than those of the compounds having 1.77. The ageing stability of castor oil and PPG-based potting compounds having isocyanate index 2.54 is better than that of PEG oil-based potting compounds. Appreciable hydrolytic, oxidative and chemical stability could be observed with HDI-IC/PPG/2.54 potting compounds for development of haemodialyser, oxygenator, etc.

Studies on poly(propylene fumarate-co-ethylene glycol) based bone cement.

Poly(propylene fumarate-co-ethylene glycol) random (PPF-1) and block (PPF-2) copolymer oligomers were prepared. Comparing the setting characteristics of PPF-1 and PPF-2 with comonomer n-vinyl pyrrolidone (n-VP) and swelling characteristics of cured PPF-1 and PPF-2, lower setting temperature and setting time was observed with the former leading to higher swelling coefficient and lower cross link density in the cured PPF-1. Due to the high swelling coefficient and low setting exothermic temperature associated with PPF-1, the bone cement was prepared from PPF-1, n-VP and hydroxyapatite (HAP). The in vitro degradation studies reveal lesser weight loss and deformation of PPF-1/n-VP/HAP based cured resin in Ringer's solution and phosphate buffered saline in comparison with that of PPF-1/n-VP cured resin. Though the bone cement composite has adequate mechanical properties with HAP, the compressive strength and modulus of the composite aged in Ringer's solution and PBS reduced appreciably which is due to extensive hydration and plasticization by the PEG unit. However, the bone-binding and bond strength of the bone cement determined as the load for separation of bones was found to be similar to that of fast setting calcium phosphate-atelocollagen (5%) bone cement. The bone cement PPF-1/n-VP/HAP could be used as scaffold for correcting the bone defects.

A preliminary study on the interaction of cell-polymer extract towards biodegradation.

Two newly synthesised polyurethanes were subjected to a preliminary study, in-vitro, on the interaction of cell polymer extract to understand the phenomenon of biodegradation by employing VERO cells. VERO cells exposed to the saline extract of the polymer showed cytopathic effect with granulations in the digestive vacuoles. It is suggested that the long term material performance of an implant-material can be evaluated by using VERO cells and/or macrophages and by analysing metabolic products secreted by the cells during interaction.

Iodinated glycidyl methacrylate copolymer as a radiopaque material for biomedical applications.

Polymeric biomaterial was synthesized by copolymerizing 50:50 mol% of monomers, glycidyl methacrylate and methyl methacrylate. Iodine atoms were then grafted to the epoxide groups of glycidyl methacrylate units, rendering the copolymer radiopaque. The percentage weight of iodine in the present copolymer was found to be as high as 23%. The iodinated copolymer showed higher glass transition temperature and thermal stability in comparison with unmodified polymer. Radiographic analysis showed that the copolymer possessed excellent radiopacity. The iodinated copolymer was cytocompatible to L929 mouse fibroblast cells. The in vivo toxicological evaluation by intracutaneous reactivity test of the copolymer extracts has revealed that the material was nontoxic. Subcutaneous implantation of iodinated copolymer in rats has shown that the material was well tolerated. Upon explantation and histological examination, no hemorrhage, infection or necrosis was observed. The samples were found to be surrounded by a vascularized capsule consisting of connective tissue cells. The results indicate that the iodinated copolymer is biocompatible and may have suitable applications as implantable materials.

The effect of radiation processing and filler morphology on the biomechanical stability of a thermoset polyester composite.

The effect of radiation processing and filler morphology on the biodegradation and biomechanical stability of a poly(propylene fumarate)/hydroxyapatite composite was investigated. Radiation processing influenced both cross-linking and biodegradation of the composites. Irradiation with a dose of 3 Mrad resulted in enhanced cross-linking, mechanical properties and a higher storage modulus which are favourable for dimensional stability of the implant. The particle morphology of the added hydroxyapatite in the highly cross-linked state significantly influenced the biomechanical and interfacial stability of the composites. Reorganization of agglomerated hydroxyapatite occurred in the cross-linked polymeric matrix under dynamic mechanical loading under simulated physiological conditions. Such a reorganization may increase the damping characteristics of the composite.

Effect of hydroxyapatite on the biodegradation and biomechanical stability of polyester nanocomposites for orthopaedic applications.

The effect of hydroxyapatite (HAP) on the performance of nanocomposites of an unsaturated polyester, i.e., hydroxy-terminated high molecular weight poly(proplyene fumarate) (HT-PPFhm), was investigated. A thermoset nanocomposite was prepared with nanoparticles of calcined HAP (<100 nm, rod-like shape, filler content 30 wt.%), HT-PPFhm and N-vinyl pyrrolidone, dibenzoyl peroxide and N,N-dimethyl aniline. Two more nanocomposites were prepared with precipitated HAP nanoparticles (<100 nm rod-like shape) and commercially available HAP nanoparticles (<200 nm spherical shape), respectively. Calcined HAP nanoparticles resulted in very good crosslinking in the resin matrix with high crosslinking density and interfacial bonding with the polymer, owing to the rod-like shape of the nanoparticles; this gave improved biomechanical strength and modulus and also controlled degradation of the nanocomposite for scaffold formation. The tissue compatibility and osteocompatibility of the nanocomposite containing calcined HAP nanoparticles was evaluated. The tissue compatibility was studied by intramuscular implantation in a rabbit animal model for 3 months as per ISO standard 10993/6. The in vivo femoral bone repair was also carried out in the rabbit animal model as per ISO standard 10993/6. The nanocomposite containing calcined HAP nanoparticles is both biocompatible and osteocompatible.