Musculoskeletal ailments are a primary cause of disability in the United States. As reported by the United States Bone and Joint Initiative ( http://www.usbji.org ), with a nearly $950-million burden weighing on the healthcare system, there is a considerable and growing need for advanced treatments for a variety of orthopedic conditions, especially as patients continue to desire to maintain an active lifestyle well into their golden years.
Raising Bioresorbable Material Expectations
Compliance mismatch between tissue and an implant is a chief cause of product failure in a variety of medical implants, including those used in orthopedic applications. It stems from a material’s lack of mechanical compliance and biocompatibility. To improve on this failed relationship, there is a need for bioresorbable polymers that use metabolic building blocks that are resorbed by the body. By assisting in cellular processes and enabling the body to manage self-healing, a truly bioresorbable material will promote endogenous tissue regeneration. However, the most commonly used bioresorbable polymers (lactides and glycolides) do not meet the expectations for newer medical implants, nor do they meet the needs of regenerative medicine.
The emergence of poly(glycerol sebacate), also known as PGS, has introduced the potential to create products that enable healing without the chronic inflammation seen with other bioresorbable materials. Since the material closely simulates the modulus of human tissue and its hydrophilicity is similar to native cartilage, it could provide a versatile platform for future regenerative orthopedic applications, from tissue engineering to drug delivery. (See Figure 1)
PGS was developed in the laboratory of Robert Langer, PhD, at the Massachusetts Institute of Technology, alongside Yadong Wang, PhD, who is currently the William Kepler Whiteford professor in Bioengineering at the University of Pittsburgh. During the past 10+ years, a substantial body of research has demonstrated PGS’s ability to perform in vivo while minimizing an inflammatory response. Since the polymer synthesis process does not require the use of solvents or additives, potentially harmful byproducts that could affect the fitness of the material are not introduced.
PGS is an improvement over traditional resorbable materials such as polyglycolic acid (PGA) and polylactic acid (PLA), which are bulk-eroding materials. This means that as PGA or PLA degrade, an abrupt loss of strength occurs with the penetration of water molecules into the structure, causing sudden failure. PGA and PLA also give off acidic degradation products, leading to inflammation and scarring. Conversely, PGS is a surface-degrading material made of glycerol and sebacic acid, natural metabolites that easily enter into the Kreb’s cycle and are quickly removed from the wound space. This enables the formation of a more natural extracellular matrix without negatively interfering with the healing process. It also does not induce the formation of fibrous capsules (as seen with other bioresorbable materials) and resorbs within a 60-day period.
Within the world of orthopedics, bioresorbable polymers made from PGS have some interesting possibilities, since they can be produced in a range of consistencies, from a gel to a tough elastomeric thermoset. In addition, these polymers have potential in soft tissue repair applications, such as tendon and ligament repair, where elastomeric activity must be temporarily present to provide the physical cues for regeneration of the native tissue. Other areas of interest include functional coatings to increase device biocompatibility and controlled release of active pharmaceutical ingredients. (See Figure 2)
Coating a porous scaffold with PGS creates a product that becomes an active participant in healing. Covalent or ionic attachment of growth factors could be released in a controlled manner from the implant into the surrounding tissue. Another example is coating collagen scaffolds that contain bone morphogenic protein-2 (BMP-2).
The application of elastomeric scaffolds to induce secondary bone healing is a paradigm shift in the approach to healing bone defects, which has traditionally involved matching hard bone with a rigid material that has stiffness similar to bone. One challenge to the typical method is inducing bone growth throughout the entire scaffold. This traditional approach of primary bone healing promotes bone growth from the sides of the scaffold, which then grow to meet at the middle. In many cases, the bone in-growth stops, and parts of the scaffold are left with fibrous tissue.
However, using PGS to create a resorbable scaffold that provides a cartilage intermediary could facilitate secondary bone healing, because the area of interest first pervades with the cartilage, which then converts to bone, as reported in a paper entitled “Poly(Glycerol Sebacate) Elastomer: A Novel Material for Mechanically Loaded Bone Regeneration,” published in Tissue Engineering, Part A, 20, January 2014, pp. 45-53.
A flexible bioelastomer, PGS behaves much like the natural tissue of a bone callus (initially soft tissue), and research has already demonstrated the biocompatibility between PGS and bone cells. Work recently conducted at the University of Pittsburgh implanted resorbable porous PGS scaffolds in rabbit ulnar defects. The study revealed that PGS can serve as an osteoconductive material to heal critical-sized bony defects (defects that do not spontaneously heal to bridge tissue), thus offering a different take on the above-mentioned conventional composition of scaffolds for bone healing. Through the use of secondary bone healing, a scaffold would completely fill with bone, resorb, and then the bone remodeling process would occur. (See Figure 3)
The Next Step: Commercialization
One cannot take a one-size-fits-all approach to designing a material. Every application must consider the local environment within the body and the impact the material plays on tissue regeneration. Disruption in the materials market will occur only when there is a true understanding of the chemistry of wound healing and the chemical breakdown that occurs when introducing a product into the body. With PGS, there has been a demonstrated effort to create a safe environment within the body that enables tissue regeneration without inciting chronic immune response. While the use of synthetic materials in regenerative medicine is still relatively young, PGS has demonstrated its potential as a viable bioelastomer platform in the orthopedics industry.
This article was written by Peter D. Gabriele, Vice President, Research & Development, and Jeremy Harris, PhD, Technical Director, both at Secant Medical, Inc., Perkasie, PA. For more information, Click Here .
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