While the combination of drugs or biologics with medical devices is no longer a groundbreaking marriage of technologies, there are areas where it is making significant advances. The incorporation of pharmaceuticals with implantable medical textiles is still relatively early in development and significant possibilities are still emerging. This article examines this specific sector.
The medical device industry has undergone significant evolution in recent years, with drug delivery being a segment of particular focus for innovation. Breakthroughs in implantable drug delivery are paving the way for the next generation of drug/device combination products. The rapid adoption of drug-eluting stents has made it clear that the medical industry recognizes the value that drug delivery coupled with an implantable medical device can bring to patient care. One of the most exciting developments for the medical device industry is the possibility now to build devices incorporating growth factor-loaded fiber (Figure 1).
Proprietary processes now enable extrusion processes for drug-loading to occur at room temperature, allowing many sensitive growth factors and biologically-based agents to remain viable when loaded to fibers for the first time ever. This enables the development of growth factor loaded fibers with tailored release kinetics and a high degree of retained biological activity. These fibers are ideal for any number of implantable medical device applications that benefit from the controlled release of pharmaceutical and biological agents within the body directly to the internal sites where they are needed. This has the potential to revolutionize spinal cord repair, nerve generation, tumor remediation, dermal wound healing, and many more applications.
Medical textiles play an important role in a variety of today’s medical applications and are often a critical component for hernia and soft tissue repair or even ligament and tendon replacement. Textiles are inherently a logical choice for tissue repair and replacement due to the fibrous nature of the human body — as muscle, tendon, ligament, and even nerve tissue are constructed of fibrous tissue.
The industry has already seen the introduction of drugs to medical textiles and there is great potential for many more medical textiles to move in this direction. For example, medical device companies now market antibiotics delivered from a mesh pouch for cardiovascular devices to help prevent infection at the site of implantation.
Medical textiles of the future hold tremendous promise for tissue engineering and regenerative medicine. Beyond simple antibiotics, fibers of the future will be able to deliver growth factors to help orchestrate the wound healing process. Imagine the possibilities of medical textiles becoming scaffolding for tissue engineering and regenerative medicine applications. The scaffolding would then deliver growth factors that can selectively direct cell migration and tissue growth according to proper placement of fibers loaded with growth factors within the scaffold.
While this may sound futuristic, the technology has already been demonstrated in bench and animal studies. It has been shown, for example, that nerve growth factor (NGF) can be loaded into polydioxanone (PDO) fibers and can be slowly released over weeks. The NGF release has been shown to retain biological activity using PC12 cell assay. Biologically active NGF causes PC12 cells to get larger and sprout dendrites. The data clearly demonstrates that the NGF is biologically active as it is released from these fibers (Figure 2).
Other growth factors such as vascular endothelial growth factor have been loaded into fibers as well. Even virus particles have been loaded into fibers and implanted into immune compromised animals and show extremely efficient transfection.
For example, one study was performed by loading an adenovirus for green fluorescent protein into a fiber. This fiber was then implanted into a human pancreatic tumor implanted into an immune compromised animal. When the tumor reached about 8mm diameter, the fiber was implanted into the tumor. Figure 3 shows the tumor at explant and a large (approximately 4.0mm) diameter of nearly all green tissue showing that the virus was able to be loaded into the fiber and implanted and released with retained biological activity.
What will the future hold for fibers that can release growth factors to help direct the wound healing response? One application that seems poised to dramatically benefit from this new paradigm of growth factor loaded fibers is nerve regeneration. Both peripheral and, perhaps most importantly, central nerve regeneration — including severed spinal cord repair and vascular grafts — may soon be possible.
The incorporation of these drug-loaded fibers into new or existing medical devices can result in faster healing, improved patient compliance, and lower negative outcomes at relatively low cost. While there is still much to learn about this technology, one fact seems certain — growth factor-loaded fibers have the potential to bring about an entirely new paradigm in how we approach wound healing and regenerative medicine.
For more information, visit www.tissuegen.com.