The purpose of this research study is to test how well the investigational treatment, Engineered Skin Substitutes (ESS-W), works for covering and treating burn wounds.

The areas of the body that are treated with ESS-W will be compared to similar areas treated with the patient's own skin (split-thickness skin autograft (AG)). A skin autograft (AG) will be performed by taking healthy skin from one area of the body and placing it on the burned area.

This study is designed to evaluate the safety and efficacy of autologous engineered skin substitute (ESS-W) compared to conventional split-thickness AG for the treatment of extensive, deep partial- and full-thickness thermal burns. A matched and randomized burn site format will be used to evaluate the successful graft take on excised deep partial- and full-thickness burns when grafted with either 1) unmeshed ESS-W or 2) meshed AG (the current standard treatment of split thickness AG).

This research study is divided into five study periods: (1) Screening Period of up to one week and (2) Pre-Grafting Period, which will last approximately 35-45 days, (3) Grafting Day(s), which are the day(s) on which grafts are applied (i.e., First Graft: Day 0 and the optional subsequent Grafting Day i.e., Second Graft: Day 0), (4) Post Grafting Observation Period, which begins with 28 days follow-up after each Grafting Day(s), and continues till Post-Operative Month (POM) 6 from the last Grafting Day, and (5) Anecdotal Observation Period

Inclusion Criteria:

• Has deep partial or full-thickness thermal burns ≥50% of the TBSA and fulfills the total grafting area requirement ranging from 288 cm2 up to 5,600 cm2, divided between two (or more) recipient sites.
• Is expected to require multiple skin grafting procedures.
• Is ≥18 years and ≤40 years of age at the time of enrollment.
• Females of childbearing potential must have a negative pregnancy test prior to enrollment and agree to use appropriate birth control methods during the pre-grafting period and for three months following the last Grafting Day.
• Subject (or a legally authorized representative (LAR)) has provided written informed consent for study participation and procedures to be performed.

Exclusion Criteria:

• Has a current diagnosis of septic shock or Multiple Organ Dysfunction Syndrome, which in the opinion of the Investigator would put the potential subject at risk of serious morbidity or death by participating in the study.
• Has a current diagnosis of an invasive burn wound infection in unexcised burn wound.
• Is pregnant.
• Is a prisoner at the time of obtaining written informed consent.
• Has a documented history of allergy or sensitivity to any of the antimicrobials or reagents used in preparation and application of ESS-W including the irrigation solution used before and after grafting. These include aminoglycosides, polymyxin B, mupirocin, ciprofloxacin, amphotericin B, hydrocortisone, and insulin.
• Has a documented history of allergy or sensitivity to any of the animal products used in preparation of ESS-W. These products include bovine blood, bovine collagen, bovine collagenase, and porcine trypsin-versene.
• Has a documented history of allergy or sensitivity to glycosaminoglycan, the polymer component of ESS-W.
• Has a documented ongoing condition which could delay wound healing such as insulin-dependent diabetes mellitus, Cushing syndrome or disease, scurvy, chronic hypothyroidism, congenital or acquired immunosuppressive condition, chronic renal failure, or chronic hepatic dysfunction (Child-Pugh class B or C).
• Has a severe malnutrition or other concomitant illness which, in the opinion of the Investigator, has the potential to significantly delay wound healing.