BBI Contributing Editor

RENO, Nevada Each year's meeting of the Society for Biomaterials (Minneapolis, Minnesota) is rich with opportunities not only to catch up on the state of the art, but also to get enticing looks into the future. The diverse subjects covered in the scientific sessions at the 29th annual gathering, held at the Reno Hilton, included biomaterials for in situ tissue engineering, gene therapy delivery systems, implantable and injectable drug delivery systems, biomimetics, biosensors, nano-structured biomaterials and drug delivery systems for orthopedic, dental, cardiovascular and ocular applications. The meeting featured 320 papers and 412 posters that were presented to some 1,200 attendees.

In the surface treatments sector, SurModics (Eden Prairie, Minnesota), known for its development of the drug-eluting coating on the Cypher coronary stent for the Cordis (Miami Lakes, Florida) subsidiary of Johnson & Johnson (New Brunswick, New Jersey), is working on the next-generation stent product.

The company reported on its development of a non-heparin-based synthetic coating for use on medical devices where biological molecules are not desired. The coating is applied by using its patented PhotoLink photochemical coupling method, which forms a covalent bond of the coating agent to the device surface.

SurModics is seeking corporate partners for use of this hemocompatible coating in medical devices. The company has developed the ability to coat cells with biocompatible polymers and is working with Novocell (Irvine, California) to develop a cell-encapsulating coating for potential use in the treatment of diabetes.

STS Biopolymers (Henrietta, New York) is developing Medi-Coat polymer coatings for the controlled delivery of heparin from indwelling catheter surfaces to render them anti-thrombogenic. A range of polymers can be incorporated in Medi-Coat coatings, including polyurethanes, cellulose esters and polyvinylpyrrolidone.

The company has recently licensed to Jomed (Berlingen, Switzerland) the use of its Medi-Coat drug delivery coating for use in stents to inhibit restenosis, with clinical trials expected to begin later this year. The Medi-Coat technology is capable of releasing a single drug or a combination of drugs.

Researchers from McMaster University (Hamilton, Ontario) reported that combining polyethylene oxide (PO) with heparin endows a surface with enhanced blood compatibility. The PO improves biocompatibility by conferring resistance to nonspecific protein adsorption.

Invibio (Greenville, South Carolina), a subsidiary of Victrex (Lancashire, UK), uses pure Peek-Optima, a polyetheretherketone biocompatible thermoplastic polymer, in a ligament fixation device that is used in arthroscopic surgery for soft tissue repair and is being sold by Mathys in Switzerland. The company is using Peek-Optima in a dental bridge that is under development.

4th State (Belmont, California) uses plasma the 4th state of matter to impart specific functionality (e.g., amino, carboxyl and hydroxyl groups) to polymer surfaces. Functionalizing inert materials such as metals, ceramics and glasses is more difficult and often requires formation of a transition layer to create binding sites for the desired functional groups.

The company uses plasma-enhanced chemical vapor deposition to treat inert materials with a thin, tenaciously adhered polymeric transition layer that is then functionalized by subsequent plasma processing.

Examples of commercial applications of plasma treatment are the enhancement of polymer adhesion to orthopedic implants, improved wear resistance of implants, reduction of protein deposition on contact and intraocular lenses and improved biocompatibility and reduction of platelet adhesion to cardiovascular catheters, stents and pacemaker leads.

Spire Biomedical, a unit of Spire Corp. (Bedford, Massachusetts), is a provider of ion beam-based processes and silver ion treatments for imparting a range of surface properties including friction and wear resistance, antimicrobial properties and enhanced tissue and blood compatibility. The company is implementing a strategy to become a provider of treated medical devices that reduce device-related complications such as clotting and infection.

Spire's initial products are the Pourchez XpressO and Pourchez Retro lines of high-flow, split-tip and kink-resistant hemodialysis catheters that use processes known as anterograde and retrograde tunneling, respectively. It also is applying its optoelectronics expertise to develop novel medical products such as laser-based surgical instruments and optical health monitoring devices.

Implant Sciences (Wakefield, Massachusetts), a provider of surface treatments and thin-film coatings to the medical device industry, also has become a direct marketer and sells brachytherapy seeds for treating prostate cancer. The company is currently developing seeds containing a radioisotope, ytterbium-70, for breast implantation after a lumpectomy procedure.

Collagen, HA, biodegradable polymers

FibroGen (South San Francisco, California) presented posters on uses of its recombinant human collagen produced using its multigene technology. Scaffolds were fabricated by lyophilizing lightly cross-linked recombinant human Type I collagen and were evaluated for potential use in bone and cartilage repair. FibroGen produced a tissue sealant from recombinant human Type III collagen and found that it took significantly shorter time to stop bleeding than Instat, a bovine Type I collagen sponge. Type III collagen has a higher capacity to induce platelet aggregation than Type I collagen, but it is difficult to produce pure type III collagen from animal tissues and no Type III collagen based hemostats or tissue sealants are being marketed.

Collagen Matrix (Franklin Lakes, New Jersey) has conducted studies in rabbits of a bioactive Type I collagen-based, radiopaque coil for the embolization of a saccular aneurysm. The aim is to provide a more stable occlusion than platinum coils used at present.

Hyaluron (Woburn, Massachusetts) supplies hyaluronic acid (HA) that is extracted from rooster combs and is also made by fermentation. The company also produces oligosaccharides that are derived from hyaluronic acid and are being investigated for use as drug excipients and for their interaction with cells for possible uses in controlling cancer growth rates and accelerating wound healing.

Genzyme Advanced Biomaterials (Cambridge, Massachusetts), a unit of Genzyme Corp. (Cambridge, Massachusetts), also supplies hyaluronic acid made by fermentation and is seeking to collaborate on the use of its proprietary technologies related to surface modification and conjugates for drug delivery.

BioInvigor (Taipei, Taiwan), a new exhibitor at the Society for Biomaterials gathering, manufactures polylactide and polyglycolide biodegradable polymers for use in drug delivery systems and medical devices. The company also produces y-polyglutamic acid that can absorb up to 3,500 times its weight of water. BioInvigor has a strategic alliance with Exactech (Gainesville, Florida), Precimed in Switzerland and Tecres in Italy to market orthopedic implants, surgical instruments and bone cements in China and Taiwan.

U.S. Surgical (Norwalk, Connecticut), a unit of Tyco Healthcare (Exeter, New Hampshire), presented its new monofilament synthetic absorbable suture, Caprosyn, that is supple, easily formed into knots and has been shown to be completely absorbed in the body in 56 days. It is composed of a random tetrapolymer derived from glycolide, caprolactone, trimethylene carbonate and lactide.

Drug delivery matrices

Nanoparticles of polymers serve many functions, including encapsulation, controlled release, targeting and immunoassays. They offer stability in electrolyte solutions and biological fluids. Access Pharmaceuticals (Dallas, Texas) has developed novel hydrogel nanoparticles that coalesce in the presence of water to form strong, elastomeric biocompatible aggregates that are shape retentive. The particles are produced in water and are composed of poly (2-hydroxyethyl methacrylate) and related copolymers.

The nanoparticle aggregates can be used to trap macromolecules and can be fabricated as erodible or non-erodible systems for drug delivery applications. Areas of particular interest are for use as a bone tissue scaffold for releasing morphogenic proteins or for spinal fusion. Access Pharmaceuticals is seeking strategic partners to further develop this technology for commercial use.

Researchers at McGill University (Montreal, Quebec) described a procedure used to prepare chitosan-alginate nanoparticles for use in the development of biodegradable controlled release systems. Chitosan is a cationic polysaccharide and alginate is an anionic polysaccharide.

Polymer microshells are being investigated as drug carriers for the cancer drug doxorubicin by researchers at Case Western Reserve University (Cleveland, Ohio). An electrostatic layer-by-layer, self-assembly technique based on alternate absorption of oppositely charged components was used to produce micro/nanoshells on micro/nanoparticles such as cells, latex particles and drug microparticles.

Durect (Cupertino, California) featured its four drug delivery technologies: Saber depot injectable for peptide and protein delivery, Microdur biodegradable injectable microparticles, Durin biodegradable implant and Duros implantable drug-dispensing osmotic pump. The company is collaborating with Cardinal Health (Dublin, Ohio) for use of its Saber delivery system for developing long-acting oral gelatin capsules, and is in partnership with BioPartners (Zug, Switzerland) to develop a sustained-release a-interferon for treating hepatitis C. Durect also has a licensing agreement with Thorn BioScience (Lexington, Kentucky) to develop Saber-based veterinary products.

The Saber system uses a high viscosity base component, sucrose acetate isobutyrate, to provide controlled drug release.

Durect also has a development agreement with Voyager Pharmaceutical (Raleigh, North Carolina) for a Durin-based system for delivery of LHRH to treat Alzheimer's disease. The Duros technology is being used in the Chronogesic (sulfentanil) pain therapy system. It is in a Phase III trial for the treatment of chronic pain.

Promising academic research

Researchers at the University of Alabama at Birmingham (Birmingham, Alabama) are seeking to develop a biofeedback-controlled growth factor delivery system for enhancing wound healing. The growth factor is bound to a degradable tissue scaffold using polyethylene glycol as the linking agent.

Work on a fibrin-based tissue scaffold for delivering a neurotrophic factor for use in spinal cord regeneration was reported by investigators at Washington University (St. Louis, Missouri). A group at the University of Washington (Seattle, Washington) reported on the use of a hydrogel composed of hydrophobic (polyethylene glycol diacrylate) and hydrophilic (polylactide) polymers in cross-linked interpenetrating networks for the controlled delivery of growth factors to promote angiogenesis.

Researchers at the University of Pittsburgh (Pittsburgh, Pennsylvania) reported on the development of 3-dimensional porous scaffolds from a biodegradable poly (ether ester urethane) urea for use in soft tissue engineering. Smooth muscle cell ingrowth into the scaffold was demonstrated.

Researchers from Clemson University (Clemson, South Carolina) described porous injectable 3-D scaffolds prepared from alginate/gelatin microbeads for tissue engineering applications. Enzymatically crosslinked elastin-like polypeptide hydrogels for use as injectable cell scaffolds for cartilage repair was the subject of a presentation by investigators at Duke University (Durham, North Carolina).

Investigators at Dalhousie University (Halifax, Nova Scotia) have conducted in vitro studies on the use of calcium polyphosphate as a biodegradable scaffold for the sustained release of the antibiotic vancomycin for the localized treatment of osteomyelitis.

Researchers at Rice University (Houston, Texas) are investigating the localized delivery of nitric oxide (NO) from a bioactive hydrogel for use in the prevention of restenosis in stents and vascular grafts. The hydrogel was made by reacting polyethylene glycol N-hydroxysuccinimide monoacrylate with cysteine. The resultant copolymer was reacted with an aqueous solution of sodium nitrate to produce PEG-Cys-NO that can be photopolymerized in situ to coat tissues and release NO over an extended period of time.

Spinal focus

Raymedica (Minneapolis, Minnesota) has developed a spinal prosthetic disc nucleus, PDN, for the treatment of degenerative disc disease. Results of physical and chemical tests showed that the product can be used for long-term implantation in the lumbar spine.

The disc is made from polyacrylonitrile-polyacrylamide block copolymer. It is in Phase III trials in the U.S. and is sold in international markets.