Author(s): Ian L Valerio [*] aff1 aff2 aff3 , Paul Campbell aff4 , Jennifer Sabino aff4 , Christopher L Dearth aff5 aff6 , Mark Fleming aff3 aff7
biologic scaffolds; combat casualty care; extracellular matrix (ECM); extremity trauma; limb salvage; regenerative medicine; soft tissue regenerate; urinary bladder matrix (UBM); vascularized wound bed
The military engagements in Operations Iraqi Freedom and Enduring Freedom (OIF/OEF) have been characterized by wounds caused predominantly by ballistic and blast mechanisms of injury [1-11 ]. These wounds consist of massive soft tissue and orthopedic injuries secondary to the following mechanisms: damage due to pressure waves and forces exerted on bodily tissues, penetrating trauma, contamination with environmental particulates, burn-related tissue destruction and blunt trauma from being 'thrown' by the explosion force [12 ]. Combat casualty survivors often have high injury severity scores with increasing rates of concomitant injuries and multiorgan system involvement [ 10 ]. Their associated extremity wounds may exhibit major neurovascular disruptions, exposed orthopedic fracture(s) and tendinous injuries devoid of periosteum and/or paratenon, coupled with massive soft tissue volumetric loss. These critical injuries may be in continuity or disparate and tend to worsen with time due to tissue ischemia over the entire zone of injury and increased infection rates from the direct inoculation of particulate matter.
Throughout the care of our trauma patients, serial surgical debridement procedures are required to gain control of such wounds prior to advanced reconstruction and/or implementation of regenerative modalities to gain definitive wound coverage [10 ]. The ultimate goals of these definitive reconstruction procedures are to: achieve durable wound and/or skin coverage to recapitulate the barrier and protective roles of skin; preserve the functional capacity of extremities and residual limbs that have been affected by complex wounding mechanisms; preserve as much soft tissue, nerve, tendon, and bone as possible; and achieve stable long-term coverage, and closure of these wounds [ 8-10 ].
The magnitude and complexity of traumatic and blast wounds may require utilizing multiple techniques from the traditional reconstructive ladder/elevator, which may often be augmented with regenerative medicine and biologic wound care therapies in an effort to provide stable, definitive soft tissue coverage (Figure 1). It is not uncommon for a single combat casualty to undergo local wound care with negative pressure therapies, extracellular matrices (ECM) placement, secondary skin grafting, local/pedicle flaps and free tissue transfers (free flaps). Thus, military reconstructive teams have explored the use of novel regenerative modalities earlier within the treatment course of trauma care in the goal of successfully achieving definitive wound coverage and healing [10 ].
Traditionally, ECMs were thought to merely provide structural support for tissues; however it is now widely recognized that ECMs may have much more biologic significance. ECM scaffold materials are derived from the decellularization of many tissue sources (e.g., urinary bladder [UBM], small intestinal submucosa [SIS], dermis [D-ECM]) that arise from a number of different species (e.g., human, porcine, bovine, ovine, shark) [ 13-20 ]. ECM scaffolds consist of a tissue source specific three-dimensional arrangement of structural and functional molecules such as collagen, laminin, fibronectin, glycosaminoglycans...