Background: This work directly addresses Peer Reviewed Orthopaedic Research Program 2019, Applied Research Award; Focus Area: 'Skin-implant interface-Identification of best practices to address infection at the skin-implant interface for osseointegrated prosthetic limbs.' Osseointegrated (OI) devices are an increasingly relevant alternative to traditional socket-attached prostheses for amputees. The sockets are hard cylinders that are custom-made to fit a person's residual (remaining) limb. The use of OI devices avoids most of the numerous problems associated to the use of socket prostheses, including wounds due to friction, pressure, suction or shear stress caused by a tight socket fit as well as pain around the remaining limb, including pressure sores, suction sores and restriction of blood flow. A metal implant is surgically inserted into the end of a person's residual limb bone with an OI device. This implant then protrudes out through the skin. The metal rod will integrate into the long bone, forming a solid, stable connection as it happens with routine hip and knee replacements. A prosthetic limb then attaches to this metal rod. As a result of this stable connection to the bone, weight to and from the prosthesis is transferred directly to the patients' skeletal system. However, current OI devices are plagued by high infection rates, a major issue that has limited widespread clinical use of such systems.
Applicability/Innovation: With this research proposal, we address the general issue of prevention of infections and skin-to-implant healing and attachment for OI prostheses. We will fabricate implant coatings made of biomolecules and a surgeon-friendly glue to be used during implantation. We base our technologies in that we will incorporate at the skin/implant interface, where the implant exits the body, a bioinspired system with two tiers of protection against infection. The first tier of protection will consist of enabling a healthy, stable, and durable attachment of the skin on the surface of the implant. If the skin attachment integrity lasts, bacteria will not have access to the surface of the implant/bone, and thus they will not be able to colonize and form biofilms on those surfaces. This is how nature protects our body from infection on areas where organs protrude out through the skin. For instance, the gingival tissues in our mouth attach to teeth forming a junction that is strong, compliant, and pervasive. This gingiva/tooth attachment prevents infection of all tissues around the hard surface of the tooth. We will incorporate in our materials protein-like molecules used by cells in skin to specifically mediate skin/organ attachment. Additionally, the glue will be also based in a protein-derived material that will be activated by light, so that the surgeon will control during surgery the specific time and location for the glue to adhere skin and implant. The second tier of protection will consist of localizing/delivering antimicrobial agents at the skin/implant interface. We have selected antimicrobial peptides, which are protein-like molecules that plants and animals naturally secrete to protect themselves from invasive organisms, such as bacteria and fungus.
Timeline to Achieve Clinical Relevance: Results from this multidisciplinary project (materials engineering, biotechnology, biology, orthopedic surgery) will guide the selection of the best technology due to its biological, functional, and practicability properties. This will guide informed decisions to test this technology in animals before seeking FDA approval. The fact that our bioinspired technologies do not incorporate cells should expedite their regulatory approval and eventual use in the clinics.
Impact on Patient Care and Military Benefit: The military benefit of this approach is very high. As of this submission, nearly 1,700 Service members have sustained over 2,300 major extremity amputations. Despite excellent prosthetic care, problems with socket-suspended prostheses remain common, frequently impeding amputee function and limiting outcomes. Thus, if successful, this proposal could dramatically improve function for the vast majority of Wounded Warriors with limb loss from the conflicts in the Global War on Terrorism. It will also help thousands of Veterans Health Administration and civilian amputees. Our team has the unique benefit of strong, accomplished, and active military and civilian surgical teams focusing on amputation and sequelae, supported by strong basic science groups with a historical focus on translational medicine. This provides an essential grounding in issues directly relevant to improving short- and long-term outcomes in this high-potential, high-visibility patient population. Furthermore, given that a residual limb needs to function in a life-long manner, upper and lower extremity limbs are critical for daily activities and overall patient well-being. Combat or combat-related orthopaedic injuries occur predominately in previously-healthy young adults.
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- Congressionally Directed Medical Research Programs: $734,161.00