Description:
TECHNOLOGY AREA(S): Bio Medical
OBJECTIVE: To develop, design, and demonstrate new technology that will allow surgeons to precisely, quickly, and objectively assess the viability of tissue in order to evaluate the effectiveness of the debridement (excision) of necrotic tissue prior to skin grafting.
DESCRIPTION: The Department of Defense has an urgent need for clinical technologies that will give surgeons the ability to assess the adequacy of burn wound excision. These technologies must be able to efficiently determine tissue viability in real time and instrumentation must be easily manipulated in a surgical environment. The current clinical standard for treatment of full and deep partial thickness burn wounds is excision of the necrotic tissue followed by split thickness skin graft [1, 2]. The purpose of the excision is to remove any tissue that might serve as an inflammatory nidus or source of infection. The goal of the surgeon is to leave a wound bed containing viable tissue to which a skin graft can adhere and integrate. The primary problem with excision is the inability to objectively assess the viability of the tissue [3]. Although bleeding is typically assumed to mean the tissue is viable, this assessment is visual in nature and does not preclude the possibility that some necrotic tissue may be inadvertently left in the wound bed that may cause complications later. This potential problem leads many surgeons to simply excise the entire dermis down to the facial plane. Although this full excision precludes the inadvertent retention of necrotic tissue, skin grafts applied to fascia typically perform poorly as they adhere to the underlying tissue and undergo contraction, requiring additional surgeries to correct [4]. Although there are devices and technologies available or in early stages of development that allow assessment of tissue viability [5, 6], they are inadequate for real time diagnosis and difficult to use in a surgical setting. The most successful techniques track blood flow, measuring temperatures changes or vascular patency. The two most promising techniques are Laser Doppler Imaging (LDI) and Indocyanine green angiography (ICG), however both have significant caveats [7]. ICG requires injection of a fluorescent dye that is associated with potential severe side effects [8]. LDI has demonstrated accurate assessment of burn severity, however limitations include long scan times and superficial resolution. Comparison of LDI to the clinical standard of visual assessment shows that LDI is only superior if the burn is more than 48 hours old [9]. The goal of this project is to develop new technology for surgeons to assess tissue viability in real-time during excision of burned, necrotic tissue at Medical Treatment Facilities (military role of care 4). Once the technology is implemented successfully at role of care 4, the potential for fielding further forward in Field Hospitals (military role of care 3) or Medical Companies (military role of care 2) will be considered. The retention of viable tissue in the wound bed would improve long term outcomes following skin grafting and reduce the number of surgeries required for complete repair. Technical objectives to achieve the goals of this STTR topic include: Improved or equivalent accuracy of tissue viability assessment over existing methods. If the ability to assess viability is equivalent to other technologies, then such results should be paired with improvements in ease of use and/or response times. The device or equipment should be easily manipulated in a surgical setting. Large, bulky devices would not be acceptable. The device should have response times in the range of seconds, providing a visual image of easily interpretable tissue viability to the surgeon.
PHASE I: In the Phase I effort, a complete design of tissue viability technology should be formulated, and the fabrication procedures should be developed for representative device implementations that can assess markers of tissue viability (e.g., tissue oxygenation). It is expected that physical attributes such as sensitivities, dynamic range, and response time will be predicted as a function of the material and device structure. It is also expected that the field of view be no smaller than 10 x 10 inches for real-time assessment of tissue viability. The relative performance of the devices should be assessed. The Phase I effort should also include fabrication experiments and bench-marking that demonstrate an adequate capability for meeting the expected challenges in fabricating the proposed technology. Specific milestones include the ability to show real-time changes to the post-excisional remaining tissues such that a surgeon viewing the output could make determinations about whether or not to excise additional tissue.
PHASE II: In the Phase II effort, a prototype technology should be fabricated and demonstrated. The performance of the technology should be fully evaluated in terms of sensitivity, selectivity, dynamic range, and limit of detection. The Food and Drug Administration regulatory requirements vary depending on the device classification. As part of the phase II effort, the performer is expected to develop a regulatory strategy to achieve FDA clearance for the new technology. Interactions with the FDA regarding the device classification and an Investigational Device Exemption (IDE), as appropriate, should be initiated. Essential design and development documentation to support FDA clearance, as described in the Quality System Regulation (21 CFR 820.30), should be capture including but not limited to design planning, input, output, review, verification, validation, transfer, changes, and a design history file. The project needs to deliver theoretical/experimental results that provide evidence of efficacy in animal models. The studies should be designed to support an application for FDA clearance.
PHASE III: During phase III, it is envisioned that requirements to support an application for device clearance from the FDA should be completed. As part of that, scalability, repeat-ability and reliability of the proposed technology should be demonstrated. Devices should be fabricated using standard fabrication technologies and reliability. The proposal should include a commercialization plan for the product that demonstrates how these requirements will be addressed. It is anticipated that there could be dual-use applications for this technology in clinical monitoring of graft perfusion and revascularization and ischemia. This technology is envisioned for use in surgical intervention for severe burn wounds in fixed medical treatment facilities. As such, the technology should have both military and civilian applications. Procurement of such technology would be at the discretion of the medical treatment facility.
REFERENCES:
1: Janzekovic Z. A new concept in the early excision and immediate grafting of burns. J Trauma. 1970;10:1103“8.
2: Pape SA, Skouras CA, Byrne PO. An audit of the use of laser Doppler imaging (LDI) in the assessment of burns of intermediate depth. Burns 2001;27:233“9.
3: Devgan L, Bhat S, Aylward S, Spence RJ. Modalities for the assessment of burn wound depth. J Burns Wounds 2006;5:e2.
4: Allen J, Howell K. Microvascular imaging: techniques and opportunities for clinical physiological measurements. Physiol Meas. 2014 Jul;35(7):R91-R141.
5: Li Z, et al. Non-invasive transdermal two-dimensional mapping of cutaneous oxygenation with a rapid-drying liquid bandage. Biomed Opt Express. 2014 Oct 1;5(11):3748-64.
6: Snowden JM. Wound closure: an analysis of the relative contributions of contraction and epithelialization. J Surg Res. 1984;37:453“63.
7: Fletcher JL, Cancio LC, Sinha I, Leung KP, Renz EM, Chan RK. Inability to determine tissue health is main indication of allograft use in intermediate extent burns. Burns. 2015 Dec;41(8):1862-7.
8: Orgill DP. Excision and skin grafting of thermal burns. N Engl J Med. 2009;360:893“901.
9: Hoeksema H, Van de Sijpe K, Tondu T, Hamdi M, Van Landuyt K, Blondeel P, et al. Accuracy of early burn depth assessment by laser Doppler imaging on different days post burn. Burns 2009;35:36“45.
KEYWORDS: Split Thickness Skin Graft, Full Thickness Excision, Necrotic Tissue, Debridement, Viability
