BBI Contributing Editor

ST. PAUL, Minnesota – The 344 papers presented during the 27th annual meeting of the Society for Biomaterials (Minneapolis, Minnesota) in late April gave evidence of the broadening scope of biomaterials research, with special symposia dedicated to drug delivery and gene therapy. There were, as always, exhibitors and reports on novel biomaterials and surface modifications, especially imparting antimicrobial properties to the surfaces of medical devices.

A symposium on injectable drug delivery for localized treatment of disease, led by Professor Eugene Goldberg, reviewed research at the University of Florida (Gainesville, Florida) on the use of protein microspheres as carriers for intratumoral injection of chemotherapeutic drugs to avoid the complications of systemic therapy. Studies have been conducted using microsphere-drug compositions of nano- and supermicron particle size from bovine and human serum albumin and casein. Drugs tested were mitomycin C, daunorubicin (Adriamycin) and mitoxantrone (Novantrone).

A paper coauthored by researchers from Colorado State University (Fort Collins, Colorado), the University of Virginia (Charlottesville, Virginia) and BioCache (Richmond, Virginia) described work on the use of pooled human polyclonal antibodies delivered locally to surgical implant sites from a controlled-release hydrogel carrier to prevent biomaterial-centered infection. A murine open abdominal surgery implant model was used.

Investigators from Alfred University (Alfred, New York) described their work using an in vitro bacterial culture system on the injection of gentamicin-loaded albumin microspheres for localized treatment of bone infection (osteomyelitis), a serious complication of internal fracture fixation and other orthopedic implantations.

The use of an absorbable gel-forming doxycycline controlled-release system for treating periodontal disease was reported by researchers from Poly-Med (Pendleton, South Carolina) and Ivoclar (Schaan, Liechtenstein).

A symposium on biomaterials for gene delivery featured Professor Kam Leong as the lead speaker. He reviewed his work on the use of non-viral vectors as an alternative to viral vectors for in vivo gene transfer. Low transfection efficiency is the major obstacle to widespread use of non-viral gene vectors.

The formation of nanospheres by complexation of DNA with natural biopolymers such as gelatin and chitosan and with biodegradable synthetic polymers such as polyphosphoesters also was studied. Ongoing efforts to develop new biodegradable polycationic polymers for gene delivery were described. In a similar study, researchers from the Korea Institute of Science and Technology (Seoul, Korea) reported on the use of vinylimidazole-grafted chitosan as a polycationic carrier for non-viral gene therapy.

Allan Hoffman and associates at the University of Washington (Seattle, Washington) reported on the use of a synthetic pH-sensitive polymer, polypropylacrylic acid, to enhance in vivo gene delivery. Researchers at Cornell University (Ithaca, New York) presented on the use of silica microparticles for the enhancement of gene delivery. The silica microparticle-transfection agent complexes were shown to increase the activity of expressed protein in various cell lines.

Bond-Coat, Graft-Coat from STS

STS Biopolymers (Henrietta, New York) is working with several companies on the use of Bond-Coat, a flexible and expandable polymer, as a primer coat on coronary stents to which is applied a drug that elutes and prevents restenosis. Initial testing was performed using Taxol. STS Biopolymers also has developed Graft-Coat, a reversed-phase graft polymerization technology that allows a variety of polymer layers to be permanently bonded to difficult-to-coat polymer medical device surfaces, such as catheter lumens and oddly shaped geometries, without using plasma, gamma or UV radiation. Graft-Coat surface modification permanently adheres to most polymer surfaces, including inert substrates. It has been used to reduce the surface friction of silicone discs and septa and for antimicrobial treatment of urological catheters.

STS recently acquired MCTec (Venlo, the Netherlands), which has a process for the high-speed coating of wire. It is being used to apply to guidewires a hydrophilic polymeric coating, called Slipskin, which is comprised of a matrix of PVP and cellulose ester. The coating can be applied before the wire is formed into a coil.

SurModics (Eden Prairie, Minnesota) has licensed its PhotoLink technology to the BioChip Systems unit of Motorola for use in immobilizing segments of nucleic acids (DNA and RNA) in a patterned array on a biochip slide. SurModics introduced in 1999 its 3D-Link Activated Slide that uses PhotoLink technology to create a 3-dimensional matrix which allows for the attachment and embedding of nucleic acids to form bioarrays. SurModics is developing for Cordis (Miami Lakes, Florida), a subsidiary of Johnson & Johnson (New Brunswick, New Jersey), a polymer matrix containing Sirolimus (rapamycin) for use on its Velocity drug-eluting stent to prevent restenosis.

Victrex (Lancashire, United Kingdom) has developed PEEK, a biocompatible, thermoplastic polymer that can be used in some applications as an alternative to stainless steel, titanium and aluminum. It is currently used in spinal fusion cages and in digit prostheses and is being developed for use in other orthopedic implants, dental devices (implants, posts, screws and bridges) and cardiovascular products (heart valve frames and ventricular assist devices).

McKechnie Plastic Components (Minneapolis, Minnesota) is a supplier of proprietary bioresorbable rod stock for a contract manufacturer of injection-molded plastic parts. Its poly-L-dilactic acid (PLDLA) rods are used to fabricate maxillofacial plates and screws sold by Bioplate (Los Angeles, California), Arthrex (Naples, Florida) and Synthes (Paoli, Pennsylvania). PLDLA also is being used to develop bone fixation and suture anchoring devices which are currently made from titanium, stainless steel, nylon and polyethylene.

Fibrogen (South San Francisco, California) is developing a process for the production of recombinant human soluble gelatin having a molecular weight distribution similar to currently available animal-derived soluble gelatins. The product is being evaluated as a vaccine stabilizer by Aventis Pasteur (Swiftwater, Pennsylvania).

AorTech Biomaterials (Sydney, Australia), a subsidiary of AorTech International (Bellshill, Scotland), gave an update of its collaborative development with CSIRO (Clayton, Australia) of its Elast-Eon biostable, siloxane-polyurethanes for use in heart valves and potentially for other long-term implantable devices. Heart valve leaflets fabricated from Elast-Eon were explanted from sheep after six months and showed no degradation, calcification or propensity for thrombus formation.

Southern BioSystems (Birmingham, Alabama) sells biodegradable polymers to the pharmaceutical and medical device industries and develops products for controlled drug delivery. The company's SABER technology is being evaluated by Genentech (South San Francisco, California) for use in delivering a growth hormone and a vascular endothelial growth factor (VEGF) for angiogenesis. The SABER delivery system uses a high viscosity base component, sucrose acetate isobutyrate, to provide controlled release of an active agent. The company is collaborating with Alcon (Fort Worth, Texas) in the development of microencapsulated ophthalmic drugs and with AstraZeneca (London) for developing a sustained release injectable drug.

American Medical Systems (Minneapolis, Minnesota) was recently granted FDA approval to market its AMS 700 series penile prostheses having an antibiotic surface treatment known as InhibiZone. The drug elutes from the surface of the device when exposed to a warm, moist environment, providing antibiotic activity on the surface and in a zone surrounding the treated device. This is the first approval by the FDA of an antibiotic surface treatment for a permanent implantable device.

Nexia Biotechnologies (Ste. Anne de Bellevue, Quebec) makes complex recombinant proteins in the form of biomaterial and biopharmaceutical products. The company's most advanced product under development is Biosteel, which is made using spider silk genes and has a tensile strength of 300,000 pounds per square inch. It is very biocompatible and has potential applications as a wound closure material and as an artificial ligament.

Researchers from the University of Michigan (Ann Arbor, Michigan) reported on the use of a polymer (silicone rubber diazeniumdiolate) for the release of low levels of nitric oxide for extended periods of time to improve the biocompatibility and performance of intravascular chemical sensors. This is intended to overcome the problem of platelet activation when implanted sensors are in direct contact with blood. The polymer is designed to mimic human endothelial cells that produce nitric oxide to relax blood vessels and inhibit blood coagulation.

Surface treatments with anticrobial properties

Anticrobial surface treatments, which remain a major area for biomaterial enhancement, were as usual an area of considerable interest at this year's gathering.

Surface Solutions (Carlisle, Massachusetts) is evaluating in preclinical models a biopolymer system for delivery of genes to treat vascular disorders. The genetic material can be locally delivered with an angioplasty balloon or intravascular stent, thereby creating a depot for recombinant protein expression in the vessel wall. The objective is to alter the gene expression pattern within the targeted cells to improve the wound healing process and minimize occlusion of the vessel or, alternatively, to promote the revascularization of ischemic tissue. Research conducted by Kenneth Walsh, PhD, at St. Elizabeth's Medical Center (Boston, Massachusetts) has shown that the biopolymer can release marker genes.

Also under development by Surface Solutions is an anti-infective release coating containing silver ions and one or two other antimicrobial agents for use in urological catheters and dialysis catheters. The choice of antimicrobial agent will depend on the kind of organisms to be killed. A corporate partner is being sought.

AgION (Wakefield, Massachusetts), formerly HealthShield Technologies, uses silver ions to impart antimicrobial properties. The technology is licensed to duPont Powder Coatings (Houston, Texas) for use on painted durable surfaces such as IV stands and tool boxes. It is also used to provide antimicrobial protection to disposable elastomeric covers of stethoscope diaphragms marketed by Doctors Research Group (Wolcott, Connecticut) which are embossed with the name of a drug for promotional purposes.

Biocoat (Fort Washington, Pennsylvania) is collaborating with AgION in the development of hyaluronic acid combined with an antimicrobial agent comprising silver ionically bound to a zeolite particle for use in central venous catheters. Discussions are under way with two potential corporate partners.

Surfacine Development (Tyngsborough, Massachusetts) has developed and patented Surfacine, a permanent and transparent antimicrobial coating for extended protection from gram-negative and gram-positive bacteria. Surfacine uses silver as a non-eluting antimicrobial agent that kills on contact by its transfer into microorganisms. It differs from other silver antimicrobial technologies that deliver silver compounds non-preferentially to the microorganism's environment, rather than into the microorganism itself. This technology has been licensed to Biocompatibles (Farnham, United Kingdom) for use on medical devices. It also has potential application in consumer and industrial cleaners and disinfectants. The technology can potentially be used to treat skin-contacting articles, such as diapers, wound dressings, wipes, surgical masks and gowns, as well as non-body contacting articles, such as hospital bed rails, carpets and rugs.

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