BB&T Contributing Writer
ORLANDO – The Society for Biomaterials (SFB; Mt. Laurel, New Jersey), drew 1,400 attendees from 28 countries and featured 1,100 oral and poster presentations. Looking ahead to 2012, SFB will join with other international biomaterials societies at the 9th World Biomaterials Congress to be held in Chengdu, China.
An increasingly dominant theme at the annual biomaterials conferences is tissue engineering and regenerative medicine with many presentations on scaffolds and extracellular matrices. The use of 3 dimensional (3-D) matrices for cell growth is gaining popularity as a substitute for traditional 2-D cell culture methods. 3-D matrices can approximate cell architecture as found in tissues, organs and tumors.
Table 1
Synthetic Polymer Scaffolds for Tissue Engineering
• Matrices for cell culture and transplantation
• Conduits for guided tissue growth
• Substrates for targeted cell adhesion
• Stimulants for desired cellular response
• Non-viral vectors for gene delivery
• Carriers for controlled drug delivery
• Space maintainers of tissue defects
Anthony J. Atala, MD, Director of the Wake Forest Institute for Regenerative Medicine and Chair of the Department of Urology at Wake Forest University (Winston-Salem, North Carolina), delivered the keynote address entitled “Regenerative Medicine: Approaches to Translation.“ Atala heads a team of more than 270 physicians and researchers that focus on growing new human cells, tissues and organs with the aim of going from the bench to the bedside. He noted that “scaffolds used for growing cells outside the body should replicate the biomechanical and structural properties of the body and solid functional organs are hardest to replicate due to complex cell types and vascularity.“ The earliest success in replicating a body part was achieved by growing skin, a two-dimensional structure. The first bioengineered organ was the bladder. This was followed blood vessels, urethra, heart valves and many other organs. It has still not been possible to grow primary human peripheral nerve, liver and pancreatic cells outside the body. An innovative technique used for growing three dimensional heart structures is the inkjet printer for delivering cells instead of ink.
Antonios Mikos, PhD, Professor of Bioengineering, Chemical and Biomolecular Engineering at Rice University (Houston) and Director of the university's Center for Excellence in Tissue Engineering, received the Founder's Award from the Society for Biomaterials. Professor Mikos also serves as president of the Tissue Engineering International & Regenerative Medicine Society (Baltimore). Mikos's research focuses on orthopedics for bone and cartilage repair and on 3-D scaffolds for guiding tissue growth (see Table 1). His many research programs are listed in Table 2.
Table 2
Research Programs in the Laboratory of
Professor Antonios Mikos
• Nanocomposites for reinforcing and improving
mechanical properties of scaffolds
• Slow perfusion bioreactor for generating an extracellular matrix in tissue engineering
• Biomimetic peptide-modified hydrogels for modulating cellular function
• Cartilage repair using growth factors
• Microporous space maintainers for regenerating bone and soft tissue
• Injectable and biodegradable composite scaffolds as
carriers for bone and cartilage cells
• Absorbable microbeads for use in drug delivery and
gene therapy
James Burns, PhD, senior vice president and head of drug & biomaterial R&D at Genzyme (Cambridge, Massachusetts) was recipient of the society's Technology Innovation & Development Award. Burns reviewed that many performance requirements and lengthy development program that led to Seprafilm, a hyaluronic acid-based adhesion barrier film (see Table 3). Despite extensive efforts by other researchers to develop an anti-adhesion products, Seprafilm remains the only approved adhesion prevention product for open gynecological and abdominal procedures. It has been the subject of more than 20 clinical trials and has been used on over 2 million patients. There are still areas of improvement since Seprafilm has difficult handling characteristics and as a result is not suitable for use in laparoscopic procedures.
Companies developing products for tissue engineering
Tissue Regeneration Systems (Ann Arbor, Michigan) is developing resorbable skeletal reconstruction implant scaffolds based on the research of Scott Hollister, Professor of Mechanical and Biomedical Engineering, College of Engineering at the University of Michigan (Ann Arbor). It has a porous structure to facilitate bone integration and an osteoconductive coating to enhance bone regeneration and proliferation into the implant scaffold. It also is load bearing without the need for reinforcement with metal plates. The initial clinical application sought for this scaffold is for use in craniomaxillofacial surgery. Other potential applications are for orthopedic and spine fusion.
Table 3
Key Performance Requirements for an
Intraperitoneal Adhesion Barrier
• Appropriate bio-degradation and residence time (5-7 days)
• Tissue adherence (avoid fixation with sutures)
• Compliant with soft tissue
• Low in-situ swelling
• Effective in presence of blood
• No infection potentiation
• No interference with wound healing
• Excellent efficacy/safety profile
RegeneCure (Jerusalem) develops bone tissue engineering products for applications in trauma, spine, and reconstructive cranial and facial orthopedics as well as sports medicine. The company recently licensed exclusive rights to membrane implant technology that was invented by Professor Michael Friedman from the Institute of Drug Research at the Hebrew University and Rami Mosheiff, MD, head of the Orthopedic Trauma Center at Hadassah Medical Center (both in Jerusalem). The membrane implant is positively charged and has a microporous surface that facilitates adherence of bone stem cells recruited to the injured site through the chemotaxis signaling mechanism. It optimizes proliferation and differentiation of the stem cells into bone tissue and also serves as a barrier that does not allow scar tissue to infiltrate into the fracture site. RegeneCure's scaffolding method improves natural bone healing due to the ability of the tubular implant to attract bone stem cells and rapidly form new bone tissue. The company has completed a preclinical animal study to determine safety and efficacy of the implant and intends to submit its data to the FDA for clearance by the end of this year.
3D Biotek (North Brunswick, New Jersey) uses precision 3-D microfabrication technology to develop 3-D cell culture devices for stem cell/tissue engineering, drug discovery and broad cell biology applications. Qing Liu, PhD, CEO, explained that 3-D scaffolds have significantly more viability, increased extracellular matrix secretion and longer proliferation periods, as compared to two-dimensional scaffolds. 3-D scaffolds more closely resemble the cell growth environment of the human body and yield more physiologically relevant results. Microfabrication technology is used for making scaffolds with uniform pore sizes ranging from 200 to 500 microns. 3D Biotek markets 3-D Insert scaffolds for cell culture and tissue culture applications. They are fabricated from either polystyrene or polycaprolactone (PCL), a biodegradable polymer. 3D Insert-PCL has been selected by the National Institute of Standards and Technology (NIST ; Gaithersburg, Maryland) as the standard 3-D tissue engineering reference scaffold.
3D Biotek sells the 3-D Cell Transfection Kit that was co-developed with BioCell Challenge (Toulon, France) and is based on 3D in vitro transfection technology for achieving high delivery efficiencies of plasmid DNA. The kit contains a sterile plate with 3-D scaffolds and a reagent to transfect cells growing in physiological tissue environments. 3D Biotek's products re distributed in the U.S. Europe and Asia by Sigma-Aldrich (St. Louis). The company is also working with Life Cell Technology (Frederick, Maryland), a stem cell technology company, to develop 3-D-based assays, and with Promega (Madison, Wisconsin) to develop 3-D cytotoxicity assays.
3D Biotek is also developing bone repair scaffolds based on its 3-D Insert-PCL platform. This includes a bone matrix equivalent product that is aimed at replacing the use of allograft bone matrix. This project is funded by an NIH SBIR Phase I Grant and Edison Innovative R&D grant from New Jersey Commission on Science and Technology (NJCST). Research results were reported at the conference under the abstract titled “Novel Fully Biodegradable Biomimetic Scaffolds for Bone Regeneration and Repair.“
Biomedical Structures (Warwick, Rhode Island), a supplier of biomedical textiles for medical devices, recently acquired Concordia Medical, a division of Concordia Manufacturing (Warwick), a provider if fiber-based medical implants and scaffolds for tissue repair and regenerative medicine. Concordia's Biofelt is a resorbable polymer scaffold that can be used in PMA devices for tissue engineering and cell-seeding to facilitate the growth and proliferation of cells and autologous tissues, both in vivo and in vitro.
Reinnervate (Sedgefield, UK) has developed Alvetex in collaboration with Durham University (Durham, UK). Alvetex is a thin membrane polystyrene scaffold (200µm) with a well defined and uniform porous architecture that enables homogeneous 3D cell growth. The cells maintain a 3-D shape and form close interactions with adjacent cells. The material is compatible with a broad range of standard molecular and cellular techniques used to analyze cultured cells.
Tengion (East Norriton, Pennsylvania) is a clinical-stage biotechnology company that is creating products intended to harness the intrinsic regenerative pathways of the body to produce native-like organs and tissues. Its Organ Regeneration Platform is based on intellectual property developed by Tengion and is licensed from Children's Medical Center (Boston) and Wake Forest University. The company's lead product candidate, the Neo-Urinary Conduit, is in clinical trials. It is an autologous implant that is intended to catalyze regeneration of native-like bladder tissue for bladder cancer patients requiring a urinary diversion following bladder removal (cystectomy). Tengion's lead preclinical program is Neo-Kidney Augment which has been shown to delay or prevent renal failure in several preclinical models of chronic kidney disease. Tengion raised $31.4 million in March 2011 from a stock sale, including an investment by Medtronic (Minneapolis).
Proxy Biomedical (Cleveland) has recently introduced AlloMEM human peritoneal tissue. The company is also developing 3-D and nano-fibrous structures made from resorbable polymers for use as tissue engineering scaffolds. Proxy Biomedical already has a portfolio of medical textile and nonwoven biomaterials that have been commercializes under its original design manufacturing business model.
Novel Biomaterials and Constructs
Poly-Med (Anderson, South Carolina), a perennial contributor to the biomaterials conference, had 2 oral and 11 poster presentations. The company was led until last August by the late Shalaby W. Shalaby, PhD, who was renown for his creative and prolific contributions to biomaterials science. Research results were reported on a series of rheologically modified absorbable tissue adhesives, branded AcryPrene, that release a low amount of heat when curing and forms a flexible and strong film that promotes healing. The major components are methoxy 2-cyanoacrylate, ethyl 2-cyanoacrylate and a stabilizer.
PolyMed also reported on a bioresorbable prophylactic bone wax containing the antibiotics rifampin and minocycline for use in the prevention of sternal wound infection. This is a common complication following cardiothoracic surgery with a reported 15% of patients being readmitted for recurrent sternal wound infection. The use of bone wax in thoracic surgery can be employed as an aid in prophylactic treatment in addition to its conventional role as a hemostatic agent to plug the bleeding sternum.
Waleed S. W. Shalaby, MD, PhD, Chief Scientific Officer of Poly-Med, delivered a posthumous tribute titled “Novel Tailored Biomaterials from Biocompatible to Bioactive,“ in recognition of his late father's research on absorbable polymers for surgical and medical constructs and devices. This includes their use in sutures, meshes for hernia repair and reconstructive surgery, ureteral stents, and as tissue adhesives. Poly-Med has developed a drug eluting spray bandage, based on a low crystallinity absorbable copolymeric matrix, that has shown antimicrobial and antifungal effectiveness. The polymeric matrix is highly extensible and compliant. The product, named MediPrene, is currently being developed for various spray bandage products with and without active agents, with the first of these expected to be approved by FDA later this year.
Hyalose (Oklahoma City, Oklahoma) specializes in using recombinant technologies to produce hyaluronic acid (HA) with very defined polymer lengths, enabling a high level of control of functionality. This differs from other producers of HA that use extraction from an animal source or a bacterial process. The company has a portfolio of many issued and pending patents. Its marketed products include NanoHA, OligoHA and SelectHA which are also sold by several distribution partners and are used for research purposes. Hyalose has also licensed technology to Novozymes (Bagsvaerd, Denmark) for the production of HyaCure, a highly purified, animal- and pathogen-free HA made in recombinant bacteria with a green processing scheme for work requiring bulk HA without strict polymer size control. These technologies were developed by Professors Paul DeAngelis and Paul Weigel at the University of Oklahoma Health Science Center (Oklahoma City) and Dr. Wei Jung at Hyalose, an Emergent Technologies (Austin, Texas) company.
HTL Biotechnology (Javene, France) produces high purity HA from a natural bacterial strain. Its half-life is 4 days and there is no need for crosslinking to slow resorption. The company featured two new products that are just coming on stream, pharmaceutical grade chondroitin sulphate made by bacterial fermentation (non animal source) for use in ophthalmology and rheumatology, and sodium heparosan that is structurally similar to HA but is not broken down by hyaluronidase and other extracellular enzymes. Its intended uses include dermal filler, drug delivery vehicle and as an anti-adhesion coating on medical devices. It is also made by a fermentation process.
Javenetech (also in Javene), a sister company, markets marine-derived raw materials (DNA, collagen, and protamine sulfate) for use in cosmetic products. It is developing a medical grade collagen that is extracted from an Atlantic jelly fish.