BBI Contributing Editor

MEMPHIS, Tennessee The 30th annual gathering of the Society for Biomaterials (Mt. Laurel, New Jersey), held at the Cook Convention Center in late April, featured more than 700 oral and poster presentations covering a spectrum of medical applications for bioengineered, polymeric, ceramic and metallic materials. Several sessions were devoted to tissue engineering, including fabrication, cell matrix interactions, synthetic and natural matrices, urological tissue engineering as well as product regulations.

A series of symposia were convened on the use of nanotechnology for cellular engineering, drug delivery systems, orthopedic and dental applications, and for nanofabrication of biomaterials. Special sessions focused on the use of biomaterials in cell/organ therapies for cardiovascular, spinal and ophthalmic applications.

Tissue engineering has emerged in the last decade as an alternative to currently used therapies for bone and cartilage repair. This requires the use of a scaffold that serves as a 3-D template for the regeneration of neo-tissue. Also, there is a need for the development of responsive scaffolds that can reply to physiological stimuli. Several presentations on the development of novel scaffolds for tissue engineering are reviewed below.

Researchers from the University of Pittsburgh reported on the development of a class of thermosensitive, biodegradable and elastic polymers for potential application in cardiovascular tissue engineering. These thermoresponsive hydrogels were prepared from N-isopropyl acrylamide with poly(ester urethane) dimethacrylate. They are highly deformable at room temperature but firmly associate when warmed to body temperature, thereby providing the mechanical properties appropriate for use as a scaffold. These researchers also reported on the use of biodegradable elastomeric scaffolds seeded with muscle-derived stem cells for use as a vascular graft.

A laser-layered stereolithography system was used to fabricate spatio-temporally patterned poly(ethylene glycol)-diacrylate scaffolds by rese-archers at the University of Texas (Austin, Texas). This seeks to overcome the current limitations in developing multiple tissue types (i.e., bone, cartilage, muscles and ligaments) within a single scaffold structure.

Investigators at Seoul National University (Seoul, South Korea) produced nanocomposite scaffolds of collagen-derived gelatin and hydroxyapatite via a biomimetic precipitation method. The nanoscale ordered composite of apatite crystals and natural polymer maintained uniform and open pore structure and preserved the structural and biological functions of damaged hard tissues, resulting in significantly higher osteoblast cellular responses compared to conventionally mixed composites.

An acellular matrix from human amniotic membrane for use as a surgical patch and as a delivery system for epithelial cells was produced by resear-chers at the Institute of Biological and Medical Engineering (Leeds, UK). The material was rendered non-immunogenic by using a novel detergent-based protocol. The matrix appeared to be biocompatible in vitro and had no adverse effects on cell morphology.

Composite scaffolds of chitosan and poly(lactic-co-glycolic acid) were prepared by scientists at the University of Virginia (Charlottesville, Virginia) and found to have physical and mechanical properties suitable for bone tissue engineering applications. A collaborative research program by investigators at the University of Minho (Braga, Portugal), University of Minnesota (Minneapolis) and Universite de Tours (Tours, France) reported on the development of a thermoplastic composite of chitosan and a polyester for use as a scaffold that can be processed by melt-based routes for use as bone and cartilage tissue engineering applications.

Researchers at MacroPore Biosurgery (San Diego) reported on a compression molding technique for fabricating porous polymeric scaffold sponges without using organic solvents. Scaffolds with heterogeneous pore sizes and biologically relevant shapes can also be produced. A study demonstrated that the porosity is most significantly controlled by the polymer sheet thickness and platen temperature.

Modified fibrin hydrogels were evaluated and show promise as scaffolds for articular cartilage tissue engineering by a team from the University of Ottawa, the National Research Council and Ottawa Hospital (all Ottawa, Ontario). The fibrin hydrogels were non-cytotoxic and displayed a positive effect on extracellular matrix expression and secretion by the cells.

Treatment of back pain, spinal cord injuries

Low back pain is among the most commonly reported medical symptoms and ranks third in leading to medical procedures. Degenerative disc disease is a major cause of low back pain. One possible solution for low back pain could be an injectable carrier that provides long-term pain relief without destroying the disc. A microsphere-dispersed in situ forming hydrogel matrix that contains a pain-relieving drug was reported by investigators from the University of Iowa (Iowa City, Iowa). The microspheres were prepared from e-caprolactone by melt encapsulation and bupivacaine was used as the analgesic.

Researchers at the Georgia Institute of Technology and Emory University (both Atlanta) are developing in situ gelling hydrogels for filling defects of the spinal cord. Embedded within the hydrogel scaffolds are lipid microtubules that slowly release brain-derived neurotrophic factor for its neuroprotective effect.

A fast-gelling polymer material that is injected into the intrathecal space at the site of a compression injury of the spinal cord is being researched at the Toronto Western Research Institute and the University of Toronto. The fast-gelling drug delivery vehicle is comprised of methylcellulose and hyaluronic acid and releases erythropoietin (EPO) over three days. EPO has been shown to provide neural protection and to minimize secondary injury with a therapeutic window of one to three days.

Biomaterials and surface treatments

Invibio (Greenville, South Carolina), a subsidiary of Victrex (Lancashire, UK), provides biocompatible thermoplastic polymers for use in medical devices. PEEK (polyetheretherketone) polymers have strong chemical resistance. Invibio's PEEK-Optima is for use in implantable medical devices having blood or tissue contact for more than 30 days and PEEK-Classix is for medical device applications requiring blood or tissue contact for less than 30 days. PEEK-Optima is used in spinal implants, including a spinal cage and spinal screws sold by Surgicraft (Worcestershire, UK) and in spinal cages marketed by NuVasive (San Diego) and Scient'x (St. Qunetin En Yvelines, France).

Ionbond (Rockaway, New Jersey) offered its Medthin line of biocompatible, wear-protective, thin-film physical vapor deposition (PVD) coatings that reduce the release of metal ions and increase the wear life of orthopedic and dental devices, implants and instruments. Additional applications for its PVD coatings are for reducing the reflection from surgical instruments of operating theatre lights and reducing allergies related to implants.

Spire Biomedical, a subsidiary of Spire Corp. (Bedford, Massachusetts), featured its IonGuard ion implantation to increase hardness and reduce polyethylene wear, extending the life of spinal implants and joint prostheses. Its IonTite hydroxyapatite coatings are used for promoting bone/implant interfacial bonding and IonJoin is a surface treatment that is used to enhance bond strength of polymethyl methacrylate bone cement to ultra-high-molecular-weight polyethylene.

Phasex (Lawrence, Massachusetts) provides a supercritical fluid extraction service for preparing high purity polymers for use in medical and pharmaceutical products.

Genzyme Advanced Biomaterials (Cambridge, Massachusetts), a subsidiary of Genzyme Corp. (also Cambridge), supplies sterile, medical-grade sodium hyaluronate powder in a broad range of molecular weights. Lifecore Biomedical (Chaska, Minnesota) also offers sodium hyaluronate and aseptic processing services required to make a finished product.

NovaMatrix (Berkeley, California) supplies ultra-pure sodium hyaluronate made via fermentation and is available at varying viscosities. The company also is a leading commercial supplier of ultra-pure chitosan and alginates that are used in wound care products and drug delivery systems.

Hyaluron (Burlington, Massachusetts) has discontinued its role as a supplier of sodium hyaluronate and has expanded its facility for providing sterile fill contract manufacturing services.

Brookwood Pharmaceuticals (Birmingham, Alabama) was spun out from the drug delivery group at the Southern Research Institute (also Birmingham) and provides contract research and manufacturing of microparticles, injectable solid implants and biodegradable (polylactide/glycolide) polymers. Its subsidiary, Lakeshore Biomaterials (also Birmingham), was formed by the recent acquisition of the Medisorb polymer business from Alkermes (Cambridge, Massachusetts) and provides commercial scale-up of bioabsorbable polymers for pharmaceutical formulations and medical devices.

Other exhibiting companies that also are suppliers of polylactide/glycolide bioabsorbable polymers for drug and medical device applications include Absorbable Polymers International (Pelham, Alabama), a subsidiary of Durect (Cupertino, California); Boehringer Ingelheim (Ingelheim, Germany); Purac America (Lincolnshire, Illinois), a subsidiary of CSM (Diemen, The Netherlands); and Ortec (Piedmont, South Carolina).

PolyNovo Biomaterials (Melbourne, Australia), an operating division of Xceed Biotechnology (Perth, Australia), is developing biodegradable polymers for use in medical devices. These include injectable systems for minimally invasive surgical procedures, NovoSorb bone cement and bone substitute, and a range of thermoplastics which can be used in injection molding, extrusion and solution processing. The company has entered into a collaborative agreement with an unidentified international medical device company in the field of stent coatings and fully biodegradable stents.

Inamed (Santa Barbara, California), a marketer of collagen-based dermal implants, has begun selling to other companies and researchers its PureCol purified sterile bovine Type I collagen for use in tissue engineering, cell cultures and biochemistry. Inamed announced its plans to begin selling a purified sterile human collagen.

FibroGen (South San Francisco, California) plans to market its recombinant collagen for use in medical devices and therapeutics.

MediVas (San Diego) presented positive results from in vitro and in vivo preclinical porcine model studies on the blood and tissue compatibility of its bioanalogous amino-acid-based poly(ester amide) copolymers, known as PEAs. These copolymers do not undergo hydrolytic bulk erosion like polylactide/glycolide copolymers but rather degrade by enzymatic surface erosion. They have excellent biocompatibility and do not induce an inflammatory or immune response. By controlling the surface erosion process of PEAs and the diffusion characteristics of a drug or biologic, MediVas can provide sustained and controlled drug release. The PEA polymers are capable of delivering drugs and biologics from a simple matrix to covalently bonded constructs.

The company has licensed PEAs to Boston Scientific (Natick, Massachusetts), Guidant (Indianapolis), Estracure (Montreal, Quebec) and MicroPort Medical Devices (Shanghai, China) as a coating in drug-eluting stent applications.

MediVas also has licensed PEAs to Afmedica (Kalamazoo, Michigan) for use in a drug-eluting wrap that is placed around the outside of a blood vessel or graft to maintain patency of the graft.

PEAs also are being tested in animals for use in the sustained delivery of drugs to the back of the eye for treating macular degeneration and for a variety of protein delivery products, such as peptide, whole protein and DNA-based vaccines. Another area under development for PEAs is tissue-targeted drug delivery using nano and microspheres coated with ligands to cell-surface receptors, including monoclonal antibodies covalently bound to the surface of the delivery particles.

AorTech Biomaterials (Mulgrave, Australia) announced its research program to develop a breast implant using its Elast-Eon biostable silicone-polyurethane copolymer to replace polydimethyl siloxane-based silicones that are currently used as shells of saline and gel-filled breast implant devices. Silicone shells are prone to mechanical failure, are susceptible to gel leakage and are radio-opaque. The Elast-Eon shells are claimed to have superior mechanical properties and can be manufactured with different thermoplastic processing techniques. An Elast-Eon gel has been produced that can be tailored to the right viscoelastic properties suitable as a filler material. AorTech is seeking a corporate partner with which to collaborate on this development program.

AST Products (Billerica, Massachusetts) has developed several proprietary polymeric coatings for use on medical device to impart varied properties. These polymers include polyurethane, polyvinyl pyrrolidone and polyethylene oxide.

LubriLAST is a hydrophilic polymer coating that provides lubricity and is used on balloon catheters and microcatheters. HydroLAST is a coating that enhances wettability and wicking of polymeric biomaterials and is used on contact lenses. VascuLAST is a surface treatment for use on drug-eluting stents. pHreeCOAT modulates surface pH to prevent encrustation from the deposition of seed crystals and is used in urethral stents.

SurModics (Eden Prairie, Minnesota) is seeking to license its implanted helical coil that releases triamcinolone for the treatment of diabetic macular edema and age-related macular degeneration.

Polymer Technology Group (Berkeley, California) is working with several companies on spinal discs using CarboSil, its silicone polycarbonate-urethane. The company has initiated the development of ultrahigh molecular weight polyethylene for use in orthopedic implants. Polymer Technology's largest revenue source is its family of silicone hydrogels used in contact lenses.