The use of autologous skin cell suspension (ASCS) allows for the preparation and spray application of a non-cultured skin cell suspension in lieu of, or to augment, standard meshed split-thickness skin grafts (STSG). This technique promotes epidermal regeneration and rapid wound healing, while reducing the amount of skin harvested to cover large burns (up to 80:1 expansion). Previously, the use of ASCS in the US was limited to investigational use; however, a device is now FDA-approved and will likely be used to treat burns. Given the unique nature of this grafting technique, it is valuable to disseminate our experiences with ASCS post-operative wound management gained during participation in 2 FDA trials. Patients who presented with a life-threatening burn injury and lacked adequate STSG donor sites were enrolled into a prospective, uncontrolled, observational, compassionate-use study evaluating the use of ASCS for burn treatment. ASCS was directly applied to partial-thickness burns or in combination with widely meshed STSG for full-thickness burns. Post-operatively, the treated areas were dressed with high-density polyethylene (HDPE), bismuth-petroleum gauze (BPG), and an absorbent gauze layer that were secured in place with retention dressings. On POD2 and POD4, all outer layers of dressing were changed, leaving only the HDPE in place. If there was concern for infection, a silver-impregnated dressing was substituted for the BPG. On POD6, all dressings were removed and replaced with daily BPG or emollients. There were 243 wounds treated in 27 patients. The mean age was 24.6±19.3 years, with 52% being male and 48% female. Burn size ranged from 20–91% TBSA (mean 50±16%). At 8 weeks postop, 96% of the evaluable wounds had ≥95% wound closure. Minimal re-grafting was required in 10% of the wounds. Twenty-nine (12%) wounds required scar contracture release. The gold standard for skin grafting has been STSG, and numerous post-operative dressings serve as acceptable options in the burn community. ASCS is a new, relatively delicate grafting technique. The wound care following the use of ASCS is critical to achieve optimal healing outcomes. Its delicacy should not discourage providers, as we have shown remarkable results with optimal wound healing using a minimal-cost and low-maintenance dressing regimen. An Autologous Cell Harvesting Device is now FDA approved and will be available for greater use. It is important to share experiences and knowledge gained with others burn care providers to ensure optimal outcomes for all burn patients.

Assessing severity of burns based on current clinical methods is difficult but critical in assuring appropriate and expedient burn care. We are continuing to develop a novel device which uses multispectral imaging (MSI) and artificial intelligence (AI) algorithms to aide in determination of burn severity and healing potential. Previously, we reported interim results of this proof-of-concept (POC) case series at the Southern Regional Burn Conference in 2018. We now present final results of this clinical study and demonstrate feasibility for training AI algorithms to predict non-healing burn. Subjects with various burn severities were enrolled within 72 hours of burn and imaged daily with our device up to 7 days post burn. True severity of burns in each image was determined using healing assessments at day 21 post-burn and punch biopsies obtained at time of surgery. The accuracy of the imaging device to identify and differentiate healing and non-healing burn tissue in first, second, and third degree burn injuries was analyzed. Using the accuracy results, we trained an AI algorithm to identify non-healing burn tissue. Evaluation of biopsy utilization in informing the truthing method for burns was also evaluated. Data were collected from 25 subjects with 43 total burns and 303 images. The AI algorithm was trained and achieved a 90.0% sensitivity and 90.2% specificity in predicting non-healing burn tissue using cross validation. Example images for a non-healing burn on the anterior left thigh of an 86-year-old male taken 4 days post-burn injury appear in the attached figure. The AI algorithm trained on 25 subjects had an area under the curve (AUC) of 0.965, compared to an AUC of 0.850 for 10 subjects. Future work is focused on initiating a multi-center study to collect a larger representative burn database used to further train our AI algorithm. This study shows results from a completed POC study for developing an aid to burn assessments. Performance of AI algorithms trained on the data collected using our MSI device gives high confidence that clinically relevant predictions of burn healing potential are feasible using this technology.

Our Burn Center participated in the compassionate use of an Autologous Cell Harvesting Device (ACHD) for the treatment of life-threatening burns in patients who lacked adequate split-thickness skin graft (STSG) donor sites (IDE 15945 NCT02992249). With the use of this new technology, traditional practices for post-operative burn therapy required modification to ensure positive surgical outcomes. Initially, after the ACHD procedure, we practiced conservative management. This was defined as strict bed-rest and no range of motion (ROM) for 7 days post-operatively. With further experience, we have updated our practices to involve more aggressive early physical and occupational therapy, and share our experiences below. Mobility guidelines applied to patients with >20% TBSA grafted or >4000 cm2 grafted with the ACHD. Divided by anatomical region, the Post-Operative Mobility Guideline prescribes: Bed-rest until POD #4; Mobility with weight bearing as tolerated and functional ROM on POD #4; Full ROM on POD #6; Orthoses PRN for immobilizing joints and maintaining ROM. We treated a total of 26 patients with 117 involved joints. Fifty percent of the patients were male, with a mean age of 25.5 ± 19.1 years, and a mean %TBSA of 51 ± 15.7%. (Refer to Table 1 for Healing Data). Anecdotally, use of the ACHD accelerated graft healing and maturation, resulting in less time for burn scar remodeling interventions. Patients initially exhibited skin and joint tightness from immobilization, however, tissue was easily manipulated to quickly regain ROM. Patients often transferred from the Burn ICU directly to inpatient rehabilitation, not requiring the same stabilization of graft healing as with STSG. Hypertrophic scarring was virtually eliminated. Pigmentation normalization was accelerated. There was less need for aggressive scar management modalities and techniques. Compression garment requirements were decreased. The ACHD allows for quicker healing, less inflammation and edema, and less scarring than typically seen with STSG. We have seen optimal functional outcome. Further study of the ACHD with respect to cutaneous functional units, as well as its impact on inpatient rehabilitation length of stay, is needed. With the introduction of new technologies, it is important to share experiences and knowledge gained with other burn care providers to ensure optimal outcomes for all burn patients. Table 1 *Graft loss at POD #6 = 12% *15% of wounds over joints required contracture release/reconstruction Table 1 *Graft loss at POD #6 = 12% *15% of wounds over joints required contracture release/reconstruction

Split-thickness autografts (STAG) are the current standard of care for the permanent coverage of deep partial-thickness (DPT) burns. However, grafting is often complicated by hypertrophic scarring and dyspigmentation. Non-cultured, autologous, cell suspension systems are potential alternatives to autografting appropriately selected burn wounds. ReCell® is a device for the rapid, point-of-care preparation and application of non-cultured, autologous skin cells that provides an expansion ratio of 80:1 but is currently limited by US law to investigational use only. We present the results of the initial FDA approval trial for ReCell®. This was a prospective, randomized, within-patient controlled, GCP-compliant, FDA IDE trial comparing ReCell® to STAG for the treatment of acute, DPT burns in adults suffering 1–20% TBSA thermal burns. Comparable burn wounds measuring 100–320 cm2 were randomized to treatment with ReCell® vs. 2:1 meshed STAG. The co-primary effectiveness endpoints were donor site healing at 1 week (superiority) and recipient site healing at 4 weeks (non-inferiority) between the ReCell®-treated and autografted wounds. Secondary effectiveness endpoints included percent epithelialization over time, pain, and patient satisfaction. Safety endpoints included graft loss, infection, scarring, and adverse events. Data were analysed by intention-to-treat (ITT) and modified per-protocol (MPP) populations, as appropriate. A total of 101 subjects across 12 US Burn Centers were enrolled (n=101 ITT, n=83 MPP). The superiority effectiveness endpoint was met for ReCell® donor site healing in the ITT population (p=0.004), and the non-inferiority effectiveness endpoint was met at -2.4% [-8.4 to 2.3%] in the MPP population for ReCell® recipient site healing vs. STAG healing. Secondary effectiveness endpoints demonstrated similar rates of epithelialization and patient satisfaction with respect to the recipient wounds, while there was significantly reduced pain and significantly higher patient satisfaction with respect to the ReCell® donor site wounds. No demonstrable safety signal was generated. ReCell® can be used to safely treat acute, DPT, thermal burns in adults with comparable wound closure and scarring outcomes, but with significantly smaller and less painful donor sites that patients clearly prefer, when compared to conventional STAG. Using ReCell® allows the burn surgeon to “graft” a DPT burn with ~98% less skin than with conventional STAG, resulting in comparable healing, reduced pain, improved aesthetics, and increased overall patient satisfaction.

Split-thickness autografts (STAG) are the standard of care for definitive coverage of burns requiring grafting. However, STAG are often complicated by scarring, dyspigmentation, and limited donor skin. Cell suspension systems are potential alternatives/adjuncts to STAG. ReCell® is a device for point-of-care preparation and application of non-cultured, autologous skin cells that provides an expansion ratio of 80:1. Currently, ReCell® is limited by US law to investigational use only. We present the results of the confirmatory FDA approval trial for ReCell®. This was a prospective, randomized, within-patient controlled, GCP-compliant, FDA IDE trial in patients >4 yoa who sustained 5–50% TBSA thermal burns requiring STAG. Comparable burns, including 3rd degree, measuring >300 cm2 were randomized to either treatment with widely meshed STAG+ReCell® over-spray or STAG alone meshed at the surgeon’s discretion (control). The surgeon chose a meshing ratio ≤3:1 for the control before randomization, and then the ReCell® wound was autografted with the next higher ratio and over-sprayed. Co-primary effectiveness endpoints evaluated the relative reduction in donor area (superiority) and recipient site healing at 8 weeks (non-inferiority) between the ReCell® and control wounds. Secondary effectiveness endpoints included subject satisfaction and POSAS scores. Safety endpoints included infection, pain, durability, scarring, and adverse events. Data were analysed by intention-to-treat (ITT) and per-protocol (PP) populations, as appropriate. A total of 30 subjects across 6 US Burn Centers were enrolled (n=30 ITT, n=26 PP). The ReCell® and control wounds were similar in size (555 ± 378 vs. 528 ± 312 cm2, p=NS), but mean donor areas were significantly reduced with ReCell® use (271 ± 124 vs. 368 ± 150 cm2, p<0.001). The superiority effectiveness endpoint was met for ReCell® wounds in the ITT population, demonstrating a significant reduction in donor skin required, and the non-inferiority effectiveness endpoint was met in the PP population for ReCell® vs. control healing. Secondary effectiveness endpoints were similar between ReCell® and control wounds. No demonstrable safety signal was generated. ReCell® is an autograft sparing technology that can be used safely as an adjunct to STAG for treating acute thermal burns that require grafting, with a significant reduction in the amount of donor skin, equivalent wound closure, and comparable scarring outcomes when compared to conventional STAG. ReCell® allows the burn surgeon to “graft” a burn with less skin than with conventional STAG, resulting in comparable healing and scarring outcomes.

After the first 24 hours, the major cause of death in burn patients is multiple organ dysfunction/failure syndrome. It is preceded by infection in 83% of burn patients, with reported septic mortality up to 65%. Since the early recognition and treatment of infection has been shown to decrease mortality from sepsis, we implemented a multidisciplinary algorithm designed to rapidly identify septic adult burn patients. Adult (≥18 y) admissions between 7/1/2014 - 6/30/2016 were identified from our registry, and all initial sepsis screens were evaluated in the EMR. Patients were screened clinically at least BID and were considered a “positive” screen if MAP <65 mmHg (SBP<90 mmHg) or if 2 of the 3 occurred: Temp >102.2; HR >120; RR >28 (or RR >10% of ventilator set rate if set rate is >24 bpm). A positive screen prompted lab work to include CBC, BMP, procalcitonin (PCT), and lactic acid (LA), per protocol. If PCT>3.0 ng/ml or LA>2.0 mmol/L, or both thrombocytopenia and hyperglycemia were present, a “Burn Code Sepsis” was initiated and included cultures, a CXR, and empiric antibiotics. A patient was then formally considered “septic” (i.e. - infected), if the cultures were positive or the CXR demonstrated an infectious process. There were 634 admissions during the 2-year period, and 61 initial positive screens. Of the 61 patients with positive screens, 47 (77%) were infected. There were significant differences in PCT levels and time to triggering a positive screen between patients with and without infections, while no difference was noted for LA, WBC, platelets, glucose, age, %TBSA burned, or temperature between the groups (Table). Defining PCT ≥3.0 ng/mL as being positive for sepsis demonstrated a 95% PPV and a 45% NPV for PCT alone. Recognition of sepsis continues to be difficult in burn patients. PCT may have a role in the early detection of sepsis. Further research is warranted. There is a high mortality rate from sepsis in burn patients. Earlier identification and treatment of sepsis may reduce mortality.

Deep partial-thickness facial burns present a particular challenge in burn care. If grafted, seams are often hypertrophic and pigmentation may be quite variable. If not grafted, variable pigmentation and hypertrophic scarring may even be worse. The purpose of this study is to evaluate our initial experience with a non-cultured, autologous, skin cell suspension technique in the management of deep partial-thickness burns of the face. Patients were included in the study as part of a compassionate use protocol utilizing a non-cultured, autologous, skin cell suspension technique in large TBSA burns. The decision for choice of treatment on face burns was decided by one senior author. Very superficial burns were treated with topical antibacterials or allograft, while clear full-thickness burns were treated with sheet autograft. Split-thickness skin grafts meshed 3:1 were used with the non-cultured, autologous, skin cell suspension as an over-spray on all scalp burns, while the face burns were solely treated with the suspension. Adult and pediatric patients were included in the series and consented for education and research photographs in compliance with institutional standard of care and protocol requirements. Outcomes analysis included subjective cosmetic parameters and number of reoperations. There were 6 total patients who sustained 5 facial and 2 scalp burns treated with the non-cultured, autologous skin cell suspension technique. This included 4 males and 2 females. The mean patient age was 20.4 +/- 17.3 years, ranging from 4.6–40.7 years. Mean follow-up was 219.2 +/- 157.6 days, ranging from 63–412 days. Re-operations in the first 3 months after treatment occurred in 33.3% (N=2) of the patients. There were no major complications and minor complication rate was 16.7% (N=1) consisting of a superficial facial hematoma. All outcomes were judged to be equivalent or superior to current techniques of split thickness skin grafting. Non-cultured, autologous skin cell suspension can be used in deep partial-thickness facial and scalp burn injuries to achieve acceptable and potentially improved aesthetic outcomes. An autologous skin cell suspension technique of re-epithelialization of deep partial-thickness burns may provide acceptable and possibly superior results to current treatments. This approach may be particularly applicable in patients with limited donor sites.

Introduction: Split-thickness skin grafts (STSG) are the standard of care (SOC) for burns undergoing auto grafting but are associated with donor skin site morbidity and limited by the availability of uninjured skin. The RECELL (R) Autologous Cell Harvesting Device (RECELL (R) System, or RECELL) was developed for point-of-care preparation and application of a suspension of non-cultured, disaggregated, autologous skin cells, using 1 cm(2) of the patient's skin to treat up to 80 cm(2) of excised burn. Methods: A multi-center, prospective, within-subject controlled, randomized, clinical trial was conducted with 30 subjects to evaluate RECELL in combination with a more widely meshed STSG than a pre-defined SOC meshed STSG (RECELL treatment) for the treatment of mixed-depth bums, including full-thickness. Treatment areas were randomized to receive standard meshed STSG (Control treatment) or RECELL treatment, such that each subject had 1 Control and 1 RECELL treatment area. Effectiveness measures were assessed and included complete wound closure, donor skin use, subject satisfaction, and scarring outcomes out to one year following treatment. Results: At 8 weeks, 85% of the Control-treated wounds were healed compared with 92% of the RECELL-treated wounds, establishing the non-inferiority of RECELL treatment for wound healing. Control-treated and RECELL-treated wounds were similar in mean size; however, mean donor skin use was significantly reduced by 32% with the use of RECELL (p <0.001), establishing the superiority of RECELL treatment for reducing donor skin requirements. Secondary effectiveness and safety outcomes were similar between the treatments. Conclusions: In combination with widely meshed STSG, RECELL is a safe and effective point-ofcare treatment for mixed-depth bums without confluent dermis, achieving short- and long-term healing comparable to standard STSG, while significantly decreasing donor skin use. (C) 2018 The Authors. Published by Elsevier Ltd.