Leveraging The Body's Healing Ability With Silk
Serica Technologies relies on bioengineering and textile engineering to develop and customize its silk fibroin-based scaffolds and grafts to optimize their function.
By Janet Bealer Rodie, Associate Editor
T extile materials and textile engineering are increasingly valued in the biotechnology field, as more and more textile-based products are developed for such applications as tissue engineering and implantation within the body to help it heal and restore function where tissue has been damaged or destroyed. Both biodegradable and nonbiodegradable fibers may be used to lend their particular properties, depending on the intended application; and knitted, woven and nonwoven structures have been developed for very specialized products that take advantage of particular structural properties.
Silk, which has a centuries-long history of medical use as a suture, is the fiber of choice for products under development at Serica Technologies Inc., a Medford, Mass.-based medical device developer and manufacturer of natural silk fibroin-based biomaterials using advanced textile engineering and biomedical production technologies. Serica plans to offer the materials as commercial, off-the-shelf nonmammalian, long-term bioresorbable grafts and scaffolds that can be implanted using standard reconstructive surgical procedures to provide support for regenerating ligaments, tendons and other connective tissues, ultimately helping the tissue return to full functionality. Its principal product is the SeriACL™ graft for use in anterior cruciate ligament (ACL) repair, but the company’s overall scope covers not only orthopaedic and sports medicine, but also aesthetic and plastic surgery as well as drug delivery solutions.
According to Dr. Gregory H. Altman, the company’s founder, president and CEO, use of the SeriACL graft would eliminate the need to harvest tissue from the patient to repair the ligament, which not only would speed recovery, but also would reduce the cost of the procedure. Preclinical trials on animals have demonstrated the success of SeriACL as well as Serica’s SeriCuff™ scaffold, an implant for rotator cuff tendon repair. Clinical trials on humans are underway in Europe, and Altman expects to commercialize the products overseas by the beginning of 2009. Serica hopes to initiate US trials next year as well.
Serica Technologies' silk fibroin-based SeriACL™ graft (top) is intended to replace tissue harvested from the patient to repair the anterior cruciate ligament (ACL) of the knee, providing a base (bottom) to be infiltrated with native cells and remodeled into functional tissue.
Quest For A Better Solution
Altman became interested in developing the silk fibroin-based biomaterials after he injured his ACL while playing football for Tufts University and endured a lengthy, arduous rehabilitation following reconstructive surgery. After graduation, he went on to earn a doctorate in biotechnology engineering at Tufts. In 1998, while pursuing his doctoral studies, he founded Serica Technologies, originally called Tissue Regeneration Inc., with his professor, Dr. David Kaplan — chair of Tufts’ Department of Biomedical Engineering and director of its Biotechnology Center — and Dr. John C. Richmond — chair of the Department of Orthopaedics at Boston-based New England Baptist Hospital and the surgeon who repaired Altman’s ACL — to develop products based on technology Altman and Kaplan were developing at Tufts. The Serica-Tufts connection continues, and Altman also serves as a research assistant in the university’s departments of Biomedical Engineering and Orthopaedics.
Dr. Gregory H. Altman, founder, president and CEO, Serica Technologies Inc.
The Advantages Of Silk
Serica has developed proprietary processes for bioengineering standard Bombyx mori silk to purify it and make it bioresorbable. “Silk is a unique protein that is made of very simple basic amino acids that the body can metabolize, but it also offers unparalleled mechanical strength,” Altman said.
“Synthetic polymers bioresorb independently from the body’s healing process. A protein-based material such as silk, following our bioengineering of it, bioresorbs as a function of the body’s healing process,” he said as he explained the advantages of silk over man-made materials. He added that a graft made from a man-made polymer and seeded with cells to regenerate tissue begins to bioresorb immediately, before the body is able to provide blood to new tissue, and the inflammation present following surgery is not conducive to cell growth.
Off-the-shelf mammalian collagen, also used as a basis for regenerating native tissue, presents other challenges in the post-surgical environment, Altman said. “Off-the-shelf collagen available as a scaffold material is not native functional collagen, and in many instances it lacks the mechanical properties needed by an ACL scaffold, for example. Mammalian collagen is much more susceptible to breakdown in that inflamed joint following surgery and goes away too quickly; and it doesn’t offer enough strength,” he explained.
In contrast, Altman said, silk fibroin has the strength to survive the three-month avascular period. Once blood begins to flow to the affected area, the body’s own healing process begins to take over, infiltrating the graft with native cells and remodeling it into functional tissue. “At that point, the body itself can begin to break down the SeriACL graft,” he said.
“Our ultimate goal is to have the body create its own functional collagen,” he continued, explaining that following surgery, the ligaments become incased in their own synovial tissue over time. “Once the graft is encased, you have a healthy growth environment within that tissue to restore functional collagen. The concept is to simply take advantage of what the body already knows how to do — in this instance, it just needs a little bit of help getting there. This is what the SeriACL graft is intended to do.”
Preclinical trials in goats implanted with the SeriACL graft demonstrated the efficacy of the silk-based biomaterial: 95 percent of the animals returned to normal gait by six months, and the graft structure was permeated by regenerated ligament and bioresorbed by 12 months. In another trial involving implantation of the SeriCuff scaffold in sheep, the animals returned to a normal gait by six days on average, and repair strength at three months improved by 42 percent compared with traditional rotator cuff repair strength.
Engineering The Structure
Beyond the silk fibroin, the textile structure also is critical to final product design. “It’s not only the micromaterial that the cell will see, but also the structure that determines the rate at which the body can penetrate the graft in order to heal,” Altman said.
Through textile engineering, the company has customized its various products to support specific healing rates according to where the graft or scaffold is to be implanted.
Altman bioengineered the silk fibroin in the laboratories at Tufts, but Tufts does not have a textile engineering department, and the bioengineering department does not include mechanical engineering. “The textile development was done at Serica — that’s one reason we formed the company,” Altman said, noting that he worked with textile engineering students and professors from schools such as the University of Massachusetts – Dartmouth. Serica’s staff now includes four textile engineers, and seven product and process engineers who have helped develop the company’s final products.
“We saw the potential in a particular biomaterial, silk. When faced with the macro-level design challenges of engineering a particular body part or tissue type, we turned to textile engineering,” he explained. “We have explored all the way from yarn production through 3-D knitting. We went from bioengineering the protein component of the fiber to understanding yarn dynamics and the appropriate types of designs that control the strength, elasticity and fatigue life of the material — all properties critical in tissue engineering. Once we understood the yarn properties, the next challenge was the tissue or scaffold structure. To translate the yarn properties to the body, that’s where the fabric engineering components have come in.”
After exploring a variety of standard yarn-manufacturing techniques, Altman and his team incorporated several of them into a semi-custom process in order to achieve the final product properties. As for the fabrics, described as 3-D engineered textiles with both knit and crochet elements, the manufacturing techniques — also customized according to the required properties of each end product — create an organized, open scaffold that the cells can penetrate, while maximizing silk’s mechanical strength.
Developing the processes and end products has involved hands-on experimentation by the company’s staff, figuring out as they went along what would work and what wouldn’t.
“We’ve really had to rely on a variety of engineering inputs to solve the problems,” Altman said. “We’re taking standard textile techniques and adapting them to create a structure that will be most receptive by the body. It’s really taking textile engineering to the next level.
“In almost everything we’ve done, we’ve had to rely significantly on our own expertise,” he continued. “We needed to have our biomedical engineers and mechanical engineers in front of the machines to work hand-in-hand with the textile engineers as different fabric formations were created. That back-and-forth led to an understanding of how we might be able to achieve our goals.”
Early on, Altman and his team realized they wouldn’t find what they needed in standard machinery or textile format. Through their collaborations, Serica’s engineers have in one instance designed machinery specifically to do what is required. In other cases, the company has worked with the machinery manufacturer to adapt standard equipment to its needs.
Engineers operate one of the multiple types of knitting machines in Serica's controlled manufacturing environment.
Facility And Operation
Serica recently expanded its facility to total 26,000 square feet of research and development, manufacturing and administrative space. Of its 30 employees, 20 are biomedical, textile and mechanical engineers, and scientists. The company plans to add four new manufacturing positions over the next year as it ramps up its manufacturing operation in preparation for commercializing its products.
The 8,000-square-foot manufacturing operation comprises a controlled, continuously monitored environment, most of which is dedicated to the textile operation. Materials allowed in that environment are limited; and controls are in place to remove oils, dust and other contaminants from the machines, many of which have been used only to process Serica’s own materials, thus eliminating chances of cross contamination. Altman said the controlled environment facilitates the company’s efforts to uphold high levels of cleanliness similar to those found in clean rooms.
The company has implemented its own quality control system in order to provide continuous feedback to its textile engineering team. It also has entered its first preliminary audit for certification to the ISO 13485 standard, which specifies quality management system requirements for the manufacture of medical devices. Altman hopes to receive certification by the end of the first quarter of 2008.
Serica has received funding from both public and private sources to help it set up its operation and develop its processes and products.
“You have to take control of the manufacturing process, but to implement that for a medical device is certainly a resource-intensive endeavor,” Altman said. “I can’t set up in a factory — I have to set up in a controlled environment because our materials are designed to survive the rest of their lives in a patient’s body.”
Early funding came from the National Institutes of Health, the National Science Foundation, the American Orthopaedic Society for Sports Medicine, and friends and family; but a grant from the National Institute of Science and Technology (NIST) in 2004 was key in terms of textile engineering developments.
“The NIST grant really propelled us into textile engineering functionality,” he said. “The grant is given to companies to take on high-risk programs, and via their support we were able to expand our expertise in textile engineering so we could develop our SeriCuff scaffold. That funding led to venture capital financing for $5 million. In February 2007, we closed another round for $12 million.”
Altman believes the biomedical field offers good opportunities for textile engineering students. “I hope people can realize its value in biotechnology such that we keep the academic programs strong,” he said.
Serica's Product Line
Serica’s core orthopaedic products are the SeriACL™ graft for anterior cruciate ligament (ACL) repair and the SeriCuff™ scaffold for rotator cuff tendon repair. For plastic surgery applications, it is developing the SeriFascia™ surgical scaffold, a general mesh designed to support body wall reconstruction and plication; and Eplica Fascia™ customized scaffolds to support the face, neck, breast or abdominal wall beneath the skin surface.
The company also is developing SeriGel™ and Eplica Silk™ injectable hydrogels, derived from silk fiber dissolved into a water-based solution, for tissue repair. Serica is able to control the gels’ viscosities, mechanical properties and the way they bioresorb in the body.