BBI Contributing Editor

TAMPA, Florida — The 280 papers and 429 posters presented at the 28th annual meeting of the Society for Biomaterials (Minneapolis, Minnesota) in late April covered the ever-increasing and diverse range of biomaterials research. Sessions included papers on nano-structured biomaterials; biomaterials for orthopedic, ophthalmic and cardiovascular applications; stem cell-based therapies; cellular and tissue responses to drug delivery systems; and cell/organ therapies, among others. There were a large number of reports and exhibitors on novel biomaterials and surface medications of medical devices.

Surface modifications and coatings

Surface Solutions Laboratories (Carlisle, Massachusetts) is investigating the use of plasmid DNA coated on a coronary stent as a means for preventing restenosis. The DNA is taken up and expressed by smooth muscle cells and macrophages. The aim is to alter the gene expression pattern within the targeted cells to minimize occlusion of the vessel. A device company is sought to partner in developing this product.

Implant Sciences (Wakefield, Massachusetts) develops antimicrobial, radiopaque and ceramic coatings for medical devices. Its ion implantation process is used on the cobalt-chrome alloy used in knee and hip prostheses that are sold by Howmedica Osteonics (Rutherford, New Jersey), a division of Stryker (Kalamazoo, Michigan). The company markets I-Plant iodine-125 radioactive brachytherapy seeds which are produced by a unique dry manufacturing process. Implant Sciences is developing a radiopaque coronary stent and a drug-eluting stent.

AST Products (Billerica, Massachusetts) presented data on a surface coating that provides controlled release of antimicrobial agents without an initial burst effect. The coating uses a charged antimicrobial agent, such as a silver ion, that forms an ionic complex with a polymer matrix containing a counter ion, such as a carboxylic group. The silver ions are exchanged when sodium ions from physiological fluids diffuse into the coating matrix.

Quick Med Technologies (Boca Raton, Florida) described its development of absorbent materials possessing antimicrobial properties by graft-polymerization of quaternary ammonium monomers onto cellulose substrates. The covalently bound antimicrobial agent does not leach out and does not change the strength, feel or absorbency of the treated material. Potential applications include surgical sponges and dressings, diapers and feminine hygiene products.

4th State (Belmont, California) provides plasma treatment for modifying the surface properties of medical devices, including titer plates, catheters, syringe needles, stents and angioplasty balloons. As the company's name suggests, plasma is considered a 4th state of matter. Plasma processing alters surfaces and can be used for atomic cleaning, surface functionalization and surface activation for adhesion enhancement. Plasma treatment does not affect bulk properties of the treated materials.

BioSurface Engineering Technologies (Salt Lake City, Utah) has applied N-trimethylsilyl-allylamine (TMSAA) to the surface of medical devices to improve lubricity. TMSAA was applied as a monomer in a radiofrequency glow discharge plasma to produce a crosslinked coating on the surface of catheters, guidewires, stents and grafts. The surface becomes lubricious when contacted with aqueous body fluid.

Keratin, chitosan, alginate and hyaluronate

The Southwest Research Institute (San Antonio, Texas) is developing a line of keratin-based materials that are made by chemical modification of human hair. The keratins are biodegradable and can be fabricated into film, hydrogel, fiber, foam and moldable solid forms. The mechanical properties of these materials can be modified by the degree of crosslinking. Hydrogels can be made with only 2% by weight of the keratin ingredient. Applications under investigation include wound healing, tissue engineering and coatings for medical implants. Corporate development partners are being sought.

NovaMatrix (Drammen, Norway), recently acquired by FMC (Philadelphia, Pennsylvania), provides ultrapure and sterile chitosans, alginates and hyaluronates that are covered by a Master File. These biopolymers can be used to form matrices, scaffolds, gels, pastes and films for diverse biomedical and pharmaceutical applications. The hyaluronates are supplied by Kibun (Tokyo) and are made by a fermentation process.

Novel polyurethanes

Invibio (San Juan Capistrano, California), a subsidiary of Victrex (Lancashire, UK) is using its polyetheretherketone, Peek-Optima, a biocompatible thermoplastic polymer, in a heart valve that is being developed for AorTech (Bellshill, Scotland). Peek-Optima reinforced with 30% carbon fiber has recently received FDA clearance. It was reported by researchers at DePuy Acromed (Raynham, Massachusetts), a subsidiary of Johnson & Johnson (New Brunswick, New Jersey), to have a modulus of elasticity that is virtually identical to cortical bone and is being evaluated for use in a spinal fusion cage to promote graft bone stimulus and fusion. Cardiovascular applications of Peek-Optima under development at Invibio are for use in components of a ventricular-assist device, intracardiac pump, pacemaker leads and a header system. It also has application as a dental abutment healing cap. All grades of the polymer can be sterilized by conventional methods including gamma irradiation.

Polymer Technology Group (Berkeley, California) has developed a series of biostable, thermoplastic polyurethane-silicone copolymers. They have siloxane surface modifying end groups which provide resistance to surface oxidation. The company said the copolymers are being evaluated by Medtronic (Minneapolis, Minneapolis) for use as pacemaker lead insulation and are also being clinically tested in a prosthetic spinal disc to restore full motion, which offers an alternative to spinal surgery. Polymer Technology Group reported on the development of low modulus, thermoplastic polyurethane silicones that are potential alternatives to conventional thermoset silicone rubber in disposable and implanatable medical devices. The company recently licensed technology for manufacturing polyurethane biomaterials that bind heparin.

By incorporating a reactive end group into the polyurethane during synthesis, the resulting polymer readily forms complexes with heparin, thus avoiding the harsh and expensive pretreatments used with current methods of surface heparinization. A presentation on softenable, shape memory thermoplastics was made by researchers at Polymer Technology Group. These materials possess a strong temperature-dependent modulus. Thus, a catheter made from such a polymer could be inserted as a stiff plastic and upon reaching body temperature would soften dramatically to minimize damage to adjacent tissue.

Polyzen (Cary, North Carolina) produces polyurethane and silicone polymers by a dip molding process. These polymers are nonallergenic alternatives to natural rubber latex. Although more costly than latex, they are used in low-pressure balloons for cardiovascular, oncology and urology devices, surgical drains, catheter tubes, laryngoscope sheets and organ bags.

Absorbable polymers, hydrogels and collagen

Durect (Cupertino, California) has acquired Birmingham Polymers (Birmingham, Alabama) and Southern BioSystems (also Birmingham). Birmingham Polymers supplies biodegradable lactide and glycolide polymers with acid end groups for rapid degradation. They were previously supplied only on a custom basis. Southern BioSystems announced a collaboration with Cardinal Health (Dublin, Ohio) for evaluating its Saber technology for use in gelatin capsules. The Saber delivery system is a depot injectable that is useful for protein delivery. It uses a high viscosity base component, sucrose acetate isobutyrate, to provide controlled release of an active agent. Durect's other drug delivery systems include Microdur, an injectable, biodegradable microparticle; Durin, a drug-loaded biodegradable implant; and Duros, a drug-filled titanium implant that functions as a micropump and is currently used to deliver leuprolide acetate for the palliative treatment of prostate cancer. Durect's lead product under development is Chronogesic (sufentanil), a three-month continuous infusion subcutaneous implant for the treatment of chronic pain in terminal cancer patients which has completed a pilot Phase III study.

Cohesion Technologies (Palo Alto, California) is developing a 3-D polymer matrix having tissue sealant and adhesive properties which was made by introducing collagen into a hydrogel prepared from two self-polymerizing polyethylene glycol (PEG) components. The combination resulted in a polymer gel with substantially greater strength than PEG gels. The rate of polymerization of the gel can be adjusted from an instant setting for use as a sealant to setting over several minutes for adhesive applications.

Poly-Med (Pendleton, South Carolina) is developing a new family of crystalline absorbable polymers. The end-grafting of polytrimethylene succinate with traditional cyclic monomers produces a series of compliant, crystalline, absorbable polymers suitable for the production of flexible monofilament sutures.

Advanced Tissue Sciences (La Jolla, California) has investigated the use of PEG-based hydrogels for use in the reconstruction of damaged cartilage tissue. It was found that the most highly crosslinked hydrogels had compressive properties similar to that of native cartilage tissue. Other advantages of using hydrogels as scaffolding materials are its ability to retain the spherical shape of chondrocytes, the potential for improving cell seeding yields and uniform cellular distribution throughout the scaffold.

Improving orthopedic implants

Plasma-sprayed hydroxyapatite coatings are applied to joint prostheses to increase bony in-growth and improve bonding of the implant. These coatings are more widely used in Europe than in the U.S., where porous titanium coatings, made by sintering titanium beads onto the joint implant, are often preferred because of concerns about delamination of the hydroxyapatite coating and its potential for releasing ceramic particles. DePuy Orthopedics (Warsaw, Indiana), a subsidiary of Johnson & Johnson, reported the development of a technology for growing a biomimetic nano-apatite coating on a titanium substrate.

Nano-scale materials are becoming an important new category in the field of biomaterials with potential use in producing scaffold matrices, injectable and moldable materials for tissue augmentation, and bioactive coatings. Nano-scale materials offer the advantages of easy forming, low temperature processing and high flowability. U.S. Biomaterials (Alachua, Florida), developer of the Bioglass bone graft material, has prepared nano-scale bioactive glass powders by a sol-gel process for possible use in bone grafting and tissue regeneration.

Orthovita (Malvern, Pennsylvania) presented results of animal studies of its Rhakoss synthetic bone bonding material designed to replicate natural bone for use in spinal fusion devices. Rhakoss is a composite of diurethane-dimethacrylate polymer reinforced with a bioactive synthetic glass-ceramic filler for promoting bone growth. It is intended to be an allograft replacement.

Spire (Bedford, Massachusetts) introduced its IonTite line of thin (5-15 ) hydroxyapatite coatings for improved bone ingrowth in orthopedic and dental implants. Its IonJoin low-cost surface treatment is used to enhance bond strength of PMMA bone cement to titanium and cobalt-chrome orthopedic alloys, thereby increasing joint stability and lifetime of the implant. Spire recently received clearance from the FDA for its Xpresso hemodialysis catheter for use in chronic kidney dialysis. The catheter features a separated tip design that yields a high flow rate at low pressure. It is the first product that Spire will market directly.

IonBond (Madison Heights, Michigan), a subsidiary of Saurer AG (Olten, Switzerland), uses physical vapor deposition to form a variety of thin film (under 1 ) nitride coatings on surgical tools and medical implants for improved hardness, wear and corrosion resistance. IonBond has co-developed with Hayes Medical (El Dorado Hills, California) a process for applying a thick (about 12 ) textured titanium coating on cobalt chrome to facilitate bone ingrowth while maintaining the wear resistance of the cobalt chrome. It is applied to the femoral and tibial sides of a total knee prosthesis sold by Hayes Medical and is available for use by other producers of orthopedic implants. BryCoat (Safety Harbor, Florida) also featured its titanium nitride coating service.

BioMod Surfaces (Salisbury, Massachusetts) reviewed its development of a biologically active titanium surface via covalent linkage of recombinant hirudin, a potent antithrombin agent. An epoxy-based silane coupling agent was used to form the covalent bond between the oxidized surface of the titanium and a multifunctional amine spacer.