BB&T Contributing Editor

SAN ANTONIO – The Society for Biomaterials (Mt. Laurel, New Jersey) drew 1,050 attendees to this southern city during its week of Fiesta celebrations here. The conference, which featured more than 700 oral and poster presentations, started with a keynote address by Julio Palmaz, MD, who is known for the development of the Palmaz-Schatz stent two years ago.

He was the first to use coronary balloon angioplasty in humans for the nonsurgical treatment of obstructive coronary atherosclerosis. This has led to a $6 billion worldwide market for intravascular stents. The market took a big jump in 1995 with approval of the coronary stent, going from 400,000 procedures in 1995 to the current 1.5 million annual procedures.

In 2008, he formed Palmaz Scientific (Dallas) to commercialize new technologies in implantable devices developed in collaboration with the University of Texas Health Science Center at San Antonio and Johnson & Johnson (New Brunswick, New Jersey). This is the continuation of a previous venture, Advanced Bioprosthetic Surfaces, that was founded in 1999.

Palmaz gave a sobering presentation in which he characterized stent technology as being stagnant for the past 10 years. He asserted that device companies are maintaining a status of "mediocrity" and are not investing in new technologies.

He noted that most materials used today in cardiovascular devices (e.g., PTFE and Dacron grafts, cardiac valves, coronary stents and mechanical hearts) were adapted from pre-existing uses such as from aerospace, automotive and microelectronic applications.

Palmaz further explained that projects are often driven by non-scientists, and cited drug-eluting stents and biodegradable stents as examples of invalid paradigms. Despite their success, there are a small percentage of adverse reactions with drug-eluting stents.

With regard to biodegradable stent projects, it is assumed that the vascular structure will remain intact after a stent biodegrades and that it will stay functional. This assumption is not made with other structural prostheses such as joint implants. Presently, a hot area is to combine drugs and a biodegradable stent which combines the limitations of both approaches.

Palmaz recommended that cardiovascular devices be developed using a molecular mechanical approach. Cellular interactions are preceded by molecular interactions with the bio-implant. We still do not understand these processes, he said, proposing the use of functional biomolecular coatings such as CD-34 antibodies and ligand sequence surface grafting as examples of molecular mechanical approaches. He stressed the need to establish solid scientific goals and validate hypothetical mechanisms.

Wide range of device applications

Companies continue to broaden the range of polymers and copolymers that offer a wide range of properties and commercial applications in external and implanted devices .

Aortech Biomaterials (Scoresby, Australia) has developed Elast-Eon, a biostable implantable silicone-urethane copolymer that is being used in Optim pacing leads sold by St. Jude Medical (St. Paul, Minnesota), in cardiovascular cannulae from Avalon Laboratories (Rancho Dominguez, California) and as a coating on a biliary stent from Allium (Caesarea, Israel) that is marketed in Europe.

Additional products using Elast-Eon that are in development are neurostimulation leads, headers on pacemakers and spinal implants.

Poly-Med (Anderson, South Carolina) had 19 poster presentations and has been granted 15 U.S. patents in the past two years. It developed Femoseal for mechanically sealing the femoral artery. It is comprised of an absorbable copolyester and is sold in Europe by Radi Medical Systems (Uppsala, Sweden), now part of St. Jude Medical, which has future plans of marketing the product in the U.S.

Other products that are made with Poly-Med's proprietary biomaterials technology are a gluconate-releasing vaginal ringed mesh for non-hormonal contraception, a synthetic absorbable vascular graft sealant, an absorbable antimicrobial formulation for treating periodontitis that is marketed in Germany, and an absorbable cyanoacrylate-based tissue adhesive for veterinary use.

BiolineRX (Jerusalem, Israel) is developing a bioresorbable calcium alginate-based polymer that is liquid at room temperature but polymerizes to form a gel once injected via coronary catheterization into infracted tissue after a heart attack. The biomaterial, known as BL-1040, replaces the missing extracellular matrix that is damaged after a myocardial infarction and provides temporary structural support for infarct repair.

Unlike cell therapy or use of growth factors, the low-viscosity biomaterial is simple to produce and can be used off the shelf. The company has conducted pre-clinical trials on pigs and has launched a 30-patient, first-in-human clinical trial in Germany and Belgium.

ZEUS (Orangeburg, South Carolina), a leading sponsor of the Society for Biomaterials conference, manufactures precision extrusion fluoropolymers, such as PTFE and FEP (copolymer of PTFE and hexafluoropropylene), and PVDF (polyvinylidene fluoride). The polymers are available in tubing and as monofilaments and are used in access catheters, stent delivery systems, guiding catheters and guidewire introducers.

Its Absorv biomaterials platform of extruded PGA and PLA polymers are targeted for the development of a wide variety of medical products for both preventive care and the treatment of disease. Typical applications that are ever-evolving include absorbable stents, sutures, staples and anchors, microtubing for drug delivery, fracture fixation plates, pins and screws.

Zeus recently announced its entry into the field of electrospinning, a process that produces polymer fibers with thicknesses ranging from the nano to microscale. The aim is to produce electrospun polymers as fibers and fabrics with high surface to weight and volume ratios for use in controlled biological interactions and filtration media (stand alone and coding). The porous nature of the fabric allows for the formation of implantable structures within the body. Cellular growth is enabled by the electrospun fabric which acts as a scaffold to permit integration into the body.

PolyVation (Groningen, the Netherlands) produces polymers that are tailored to specific applications. Its biodegradable PEGT/PBT multi-block copolymers, based on polyethylene glycol and polybutylene terephthalate, can be made to achieve varying degrees of water absorption and swelling. They are elastomeric and thermoplastic (can be injection molded). They are not crosslinked, which differentiates them from other hydrogels.

PEGT/PBT is used as a stent coating by SurModics (Eden Prairie, Minnesota) and in SynPlug, a cylindrically shaped plug for use in intramedullary occlusion during cemented hip arthroplasty marketed by IsoTis Orthobiologics (Irvine, California), a subsidiary of Integra (Plainsboro, New Jersey).

The copolymer is being evaluated by CellCoTec (Bilthoven, The Netherlands) for use in the in situ manufacturing of tissue engineering scaffolds for cartilage repair application. Hatice Bodugoz-Senturk, a researcher in the Orthopaedic Biomechanics and Biomaterial Laboratory at Massachusetts General Hospital (Boston), reported on polyvinyl alcohol-polyacrylamide hydrogel as a promising candidate for a load-bearing cartilage substitute.

PolyVation also produces polyvinylpyrrolidone (PVP) polymers for use in the pharmaceutical industry and silicone polymers for use in ophthalmic and personal care products.

Biotectix (Ann Arbor, Michigan) is developing a new class of biocompatible, bioactive, electrically conductive polymer electrodes and coatings for enhancing the functionality of a range of external and implanted medical devices. These materials bridge the biotic-abiotic interface by joining conductive systems ionically and electronically.

They can be tailored to deliver drugs directly from the electrode site with variable delivery rates, including passive, delayed and on-demand, for promoting target tissue health and treating various diseases. The company's proprietary platform technology enables the next generation of electrodes and medical devices utilizing 100% polymer electrodes that can be grown directly in the body.

Biotectix grew out of research on conducting polymer materials which is licensed from the University of Michigan (Ann Arbor, Michigan). Biotectix is funded by Allied Minds (Quincy, Massachusetts). and received an investment in 2009 from Ann Arbor SPARK through its Michigan Pre-Seed Capital Fund.

Polyganics (Groningen, the Netherlands) is focused on the development, production and sales of synthetic bioresorbable products based on its proprietary polymer technology. The company's products include Nasopore, a post-surgery bio-fragmentable nasal dressing and Otopore, a temporary wound dressing for the outer and middle ear which degrades into fragments after several days.

These polyurethane-based products are marketed in the U.S. by Stryker (Kalamazoo, Michigan). Ascension Orthopedics (Austin, Texas) markets worldwide the Neurolac nerve guide and Flexiguide, a biodegradable surgical sheet that gives support to soft tissues, acts as an anti-adhesion barrier and maintains its mechanical properties for up to eight weeks. These products are copolymers of dl-lactide and caprolactone.

Expanding applications for modified PEEK.

PEEK (polyetheretherketone) has come to the forefront in the field of biomaterials as a radiolucent replacement for metals in devices such as spine fusion cages and craniomaxillofacial implants, due to its high strength and good wear properties compared to polymers such as UHMWPE. Modifications to PEEK continue to be made for improving its bioactive properties and further enhancing its wear performance.

Invibio (West Conshohocken, Pennsylvania), a subsidiary of Victrex (Lancashire, UK), recently introduced MOTIS, a milled carbon fiber-reinforced PEEK polymer with strong wear performance and improved stress distribution. It is intended for use in bearing applications against hard counterfaces, such as metal and ceramic. It offers an alternative to metal-on-metal combinations, thereby eliminating metal ion concerns. MOTIS is currently used in hip joints and spinal implants and is being evaluated foe use in knee implants. It is available as pellets or rods for machining.

Spire (Bedford, Massachusetts) is working with spinal implant companies for the development of hydroxyapatite coated PEEK for bone ingrowth application. It is based on technology that was previously developed for use with dental implants. PEEKGuard is a nanostructured titanium coating on PEEK that is being tested for enhanced wear resistance in a spinal spacer.

Solvay Advanced Polymers (Alpharetta, Georgia), a division of Solvay (Brussels), featured its KetaSpire PEEK, a fully thermoplastic and semi-crystalline polymer that is part of the company's Spire Ultra family of polymers.

The introductory product line has eight general purpose and high-strength grades which include high and low melt formulations for powders, unreinforced resins and resins reinforced with glass and carbon fibers. Additional formulations are under development, including fine powders and wear-resistant grades.

AvaSpire modified PEEK is a family of PEEK-based products that are tailored for specific applications. The introductory product line consists of two unreinforced grades and three glass fiber-reinforced grades. KetaSpire and AvaSpire PEEK are used in medical instruments but not in implants.

Ryan Roeder of the department of aerospace and mechanical engineering at Notre Dame University (South Bend, Indiana) reported on incorporating hydroxyapatite coating on PEEK using a plasma spray and imparting porosity by compression molding and particle leaching to enhance osteointegration for orthopedic and spine applications.

In a related research program at the Cardiff School of Biosciences at Cardiff University (Wales), PEEK was modified using oxygen plasma treatment to improve primary human osteoblast cell adhesion.

Hydrogels.

Lifecore Biomaterials (Chaska, Minnesota) has introduced for research purposes its Corgel BioHydrogel, a tyrosine-substituted sodium hyaluronate that is formed by either in vivo or in situ crosslinking by peroxidase. The technology was licensed from the Cleveland Clinic and has potential for use as a dermal filler, in microvalve repair, as well as in ophthalmology and orthopedics. The hydrogel is optically clear and can be made with a wide range of physical properties, depending on the initial hyaluronan concentration.

Keraplast Technologies (San Antonio) is collaborating with Keratec (Canterbury, New Zealand) in the development of biomaterials from naturally available keratin-containing sources. The potential medical device applications of its keratin-based products are as a coating, hydrogel. sheeting and tissue engineering scaffolds.

Mobitech Regenerative Medicine (New York) has developed a patented viscoelastic biomimetic hydrogel that is composed of hyaluronic acid and chitosan. Unlike other hydrogels, it does not require crosslinking and forms a gel at room temperature. It is malleable and maintains its structural identity for long periods, even in aqueous environments.

Pre-clinical studies have shown that all traces of the hydrogel are gone within two months. Mobitech is targeting synovial joint applications for its hydrogel and is seeking a corporate partner.

Collagen-based devices.

Covidien (Norwalk, Connecticut) featured the Permacol surgical implant, an acellular porcine collagen mesh for use in the treatment of female stress incontinence. The product came with its acquisition of Tissue Science Laboratories (Aldershot, UK).

CollaFirm (Monmouth Junction, New Jersey) is a research and development company that is focused on bovine collagen-based products for use in implants and for surgical applications. They include products for dural and spinal repair, rotary cuff (shoulder), ankle and wrist repair, as well as for ligaments and tendons.

Hydrophilic Coatings.

DSM Biomedical (Berkeley, California), a subsidiary of Royal DSM (Heerlen, the Netherlands), recently introduced ComfortCoat, a lubricious and hydrophilic coating designed to enhance maneuverability of metal guidewires in minimally invasive procedures. Hydrophilic coatings cannot typically be applied to metal guidewires because of poor adhesion properties.

Biocoat's (Horsham, Pennsylvania) Hydak hydrophilic coatings technology utilizes hyaluronan to impart lubricity to the surface of medical devices, such as vascular catheters, interventional guidewires and ophthalmic surgical devices. It is simpler to apply and is less costly than UV-cured coatings.

The company recently reported a co-marketing agreement with Agion Technologies (Wakefield, Massachusetts) to develop and promote a coatings product line featuring Agion's silver zeolite antimicrobial technology for the protection of medical devices. Coatings that release silver are currently used on central venous and urological catheters.