Case reportSecond-degree burns with six etiologies treated with autologous noncultured cell-spray grafting
Introduction
The initial clinical diagnosis of a burn wound depth usually determines the treatment, however, intermediate partial thickness burns can be difficult to classify accurately with an early evaluation [1]. Deeper partial-thickness injuries may need to undergo surgical treatment, including excision and optional split-skin mesh grafting [1], [2], [3]. Conservative treatment of extensive, deep partial-thickness wounds avoids early mesh grafting at the risk of a delay in wound closure, which may result in infection and poor aesthetic and functional outcomes. Possible complications of this therapeutic approach include hypertrophic scarring, contracture, and poor functional and aesthetic outcomes that could result in a reduced range of motion and unsatisfactory psychosocial adjustment [4]. Thus, in this borderline indication, an early autologous cell-spray grafting of extensive, deep partial-thickness wounds could be an interesting therapeutic option [5]. In addition, an enlargement of the donor-to-graft-area ratio from a routine 3:1 has its typical clinical limitation at 6:1, while using cell-spray grafting the ratio is between 20:1 and 80:1 [6], [7].
Skin regeneration is a dynamic process that involves different cell lineages and cell signaling, which leads progenitors cells to restore the tissue structure and function [8]. Epidermal burn-wound regeneration starts from the edge of the wound where the epidermal structures remain. The adjacent epidermis contains all different functional structures including the hair follicle (HF), inter follicular epidermis (IFE), and the sebaceous glands that are involved in the healing process [9], [10], [11]. Epidermal homeostasis and regeneration are enabled by quiescent epidermal stem cells (Fig. 1A), some of which can be activated and proliferate as transient amplified keratinocytes in the Stratum basale [12], [13]. Through post-mitotic differentiation and migration, cells from the basal layer can regenerate the entirely stratified epidermis [10], [14], [15], [16], [17]. In deep partial-thickness burn wounds, mesh and cell-spray grafting aim to distribute these cells over the center of the wound and speed up central re-epithelialization.
Various cell-spray grafting methods have been introduced and are thought to provide a fast re-epithelialization and then reduce the healing time and minimize complications [5], [18], [19]. This innovative technique is still under clinical evaluation and to address planned future clinical studies, suitable indications are of interest. Since 2008, skin-cell-spray grafting, using isolated non-cultured autologous keratinocytes (Fig. 1B), has been used at our center as a treatment option for 45 partial-thickness burn patients. Our chosen regulatory Innovative Practice Institutional Review Board (IRB) approach precludes a study with controls. At times, the procedure has been used in combination with mesh grafting for patients with combined second- and third-degree burn wounds. Here, we present six second-degree burn patients and their treatments, showing different burn etiologies: gas, chemical, electrical, gasoline, hot water, and tar (Table 1). In all indications, the results, after early autologous cell-spray grafting shows a fast re-epithelialization and an aesthetic and functionally satisfying outcome with no major complications. We suggest considering these indications for future clinical studies in this new field.
Section snippets
Patient criteria for study inclusion
The Institutional Review Board (IRB) from UPMC Mercy Hospital, through its Technology and Innovative Practice Assessment Committee, approved the cell-based grafting procedures under an innovative practice approach. Therefore, performing a clinical study with controls was not possible. Patient data collection for this retrospective analysis was performed under an authorization from the Institutional Review Board (IRB# PRO14010023, 23-01). Exclusion criteria for the treatment consisted of age <18
Results
Here, we present the individual clinical treatment of six patients, each with a different burn etiology, treated with cell-spray grafting:
Discussion
The clinical results of burn trauma, depending on the burn area, are often devastating and may be complicated or fatal [21]. In the USA, more than 1.25 million burns are reported per year. The NIH spends about 6.5 million dollars annually on patients wound healing projects and an excess of 25 billion is spent annually on wound treatment [22], [23]. Although cultured epidermal autografts (CEA) have been available in burn therapy for some time, the waiting time associated with the process can be
Conflict of interest
J.G. and R.E. have a financial interest in the spray-grafting device technologies through payments of RenovaCare, NY.
Author contributions
R.E. coordinated the cell-isolation process and the follow-up, analyzed data, and wrote the manuscript. J.G. and R.E designed and coordinated the manuscript design and revised the manuscript. M.C. compiled the medical records data, provided advice and revised the manuscript. M.Y. and P.O. performed the cell isolations. A.C., J.Z designed the manuscript structure, performed the cell-spray procedure and the patient follow-up. M.Y., M.C., A.C., J.Z. revised the manuscript and provided discussions.
Acknowledgments
This work was sponsored by UPMC and through gifts from RenovaCare, based in New York, NY, and the Ladies Hospital Aid Society (LHAS) through their Innovation Award (2013). We also thank Jim Harris for text corrections and editing and Dan McKeel for his help and expertise in fabricating the skin gun disposable parts.
References (27)
- et al.
Autologous skin cell spray-transplantation for a deep dermal burn patient in an ambulant treatment room setting
Burns
(2011) - et al.
The use of a non-cultured autologous cell suspension and Integra® dermal regeneration template to repair full-thickness skin wounds in a porcine model: a one-step process
Burns
(2007) - et al.
The human hair follicle contains two distinct K19 positive compartments in the outer root sheath: a unifying hypothesis for stem cell reservoir
Differentiation
(2000) - et al.
Location and phenotype of human adult keratinocyte stem cells of the skin
Differentiation
(2004) - et al.
Keratin 15 promoter targets putative epithelial stem cells in the hair follicle bulge
J Investig Dermatol
(2003) - et al.
A randomized trial comparing ReCell system of epidermal cells delivery versus classic skin grafts for the treatment of deep partial thickness burns
Burns
(2007) - et al.
In vitro keratinocyte expansion for cell transplantation therapy is associated with differentiation and loss of basal layer derived progenitor population
Differentiation
(2015) - et al.
Formation of a keratinizing epithelium in culture by a cloned cell line derived from a teratoma
Cell
(1975) - et al.
Partial-thickness burns: identification and management
Adv Skin Wound Care
(2003) - et al.
History of necrotic burn wound debridement
Polish J Surg
(2010)
Primary excision and grafting of large burns
Ann Surg
The effect of partial-thickness facial burns on social functioning
J Burn Care Rehabil
Large-mesh skin grafts
Plast Reconstr Surg
Cited by (26)
Advanced function, design and application of skin substitutes for skin regeneration
2024, Materials Today BioIn-situ bioprinting of skin - A review
2023, BioprintingAdvances in spray products for skin regeneration
2022, Bioactive MaterialsCitation Excerpt :Cell spray autografting is an innovative technique still under clinical evaluation, consisting of taking autologous skin cells from a small biopsy of undamaged skin of the patient and either spraying the cells directly over the wound or culturing them to amplify their number before spraying. In comparison to traditional sheet autografts, cell spray autografting is a simple and cost-effective method, it avoids blister formation and needs a much smaller donor site, therefore reducing healing time and minimizing complications [12,140]. Epithelial cells can be sprayed uniformly, remain viable and proliferate on the wound bed, achieving a fast re-epithelialization, which is important for a good functionality and esthetic outcome, particularly in large wounds and in joint areas [12,21,23,140].
Evaluation of the efficacy of cell and micrograft transplantation for full-thickness wound healing
2018, Journal of Surgical ResearchCell-spray auto-grafting technology for deep partial-thickness burns: Problems and solutions during clinical implementation
2018, BurnsCitation Excerpt :This method provides an on-site cell isolation process followed by the immediate application of autologous stem and progenitor cells to a freshly debrided wound bed. Cells in a saline suspension are sprayed uniformly across the wound bed to proliferate and accelerate the re-epithelialization process [17–19]. Cell-spray autografting does not preclude traditional mesh autografting, if used subsequently, and therefore could be a good early solution to address the therapeutic dilemmas attendant to deep partial-thickness burns.
Delivery systems of current biologicals for the treatment of chronic cutaneous wounds and severe burns
2018, Advanced Drug Delivery Reviews