Autologous cell harvesting

Overview

Autologous cell harvesting (ACH) is a point-of-care technology that enables preparation of a non-cultured, disaggregated suspension of autologous skin cells from a small split-thickness skin biopsy. The cell suspension, which contains keratinocytes, melanocytes, fibroblasts, and Langerhans cells, is sprayed directly onto a prepared wound bed to promote re-epithelialization [1, 2]. The RECELL System (RECELL, formerly ReCell; Avita Medical) is the commercially available and FDA-approved device for this application.

The primary advantage of ACH is donor site economy. One square centimeter of donor skin can treat up to 80 square centimeters of wound, enabling an 80:1 expansion ratio compared to the 3:1 or 4:1 ratios achievable with conventional meshed split-thickness skin grafts ^[2]. This makes ACH particularly valuable in large burns where donor site availability limits definitive closure.

Mechanism

The RECELL System processes a thin split-thickness skin biopsy (approximately 0.15 mm thick) through enzymatic disaggregation using a trypsin solution. The process takes approximately 20 minutes at the point of care and produces a heterogeneous cell suspension containing basal keratinocytes (the primary re-epithelializing cells), melanocytes (providing pigmentation), papillary dermal fibroblasts (supporting dermal repair), and Langerhans cells (providing local immune function) ^[1].

The cell suspension is delivered via a spray applicator to the prepared wound surface. Applied cells attach to the wound bed, proliferate, and differentiate to form a confluent epithelium. The inclusion of melanocytes provides physiologic pigmentation, which is not achieved with conventional meshed autografts that derive pigment only from the mesh pattern of transplanted skin ^[3].

Clinical Evidence

FDA approval trials

The FDA approved the RECELL System in 2018 based on two prospective, multicenter, within-subject controlled, randomized clinical trials.

The first trial enrolled 30 subjects with mixed-depth burns including full-thickness components ^[2]. RECELL combined with widely meshed (greater mesh ratio) STSG was compared to standard meshed STSG. At 8 weeks, 92% of RECELL-treated wounds were healed versus 85% of control wounds, establishing non-inferiority. Donor skin use was reduced by 32% with RECELL (p<0.001). Scarring outcomes at one year were comparable between groups.

The second trial enrolled 30 subjects with superficial partial-thickness burns ^[1]. RECELL alone was compared to a conventional dressing control. RECELL-treated burns healed as effectively as controls, with superior cosmetic outcomes including less hypopigmentation and less hypertrophic scarring at one year.

Comparative studies

Holmes et al. compared spray keratinocytes (ACH) with meshed STSG in a prospective study of 10 patients with partial-thickness burns ^[3]. At 52 weeks, pigmentation, color match, and Modified Vancouver Scar Scale scores were comparable between treatment groups. Pain ratings were slightly elevated in the ACH group during early healing but equalized after week 2.

Donor site expansion

A key study demonstrated that RECELL combined with a more widely meshed STSG achieves comparable healing to a more narrowly meshed STSG while reducing total donor skin harvest by approximately one-third ^[2]. This has significant implications for patients with large burns and limited donor sites, where multiple re-harvesting cycles are otherwise required.

Repigmentation

RECELL has shown particular promise for treatment of hypopigmented burn scars. The melanocyte component of the cell suspension restores physiologic pigmentation when sprayed onto dermabraded or laser-treated depigmented scars [4, 5]. This application extends beyond acute burn treatment into reconstructive burn care.

Indications

• Acute partial-thickness burns: As a standalone treatment for superficial partial-thickness burns, applied to the wound bed after debridement ^[1]
• Acute deep partial- and full-thickness burns: In combination with widely meshed STSG to reduce donor skin requirements ^[2]
• Donor site-limited large burns: Where conventional grafting cannot achieve coverage in a single operative session ^[6]
• Repigmentation of hypopigmented burn scars: Applied to dermabraded or laser-ablated scar surfaces [4, 5]
• Skin graft donor sites: Applied to donor sites to accelerate re-epithelialization ^[7]

Technique

1. Donor skin harvest: A thin (approximately 0.15 mm) split-thickness skin biopsy is taken from an unburned area. The biopsy area is approximately 1/80th the size of the treatment area.
2. Cell preparation (approximately 20 minutes): The biopsy is placed in the RECELL enzyme solution (trypsin) for enzymatic disaggregation, mechanically scraped to release cells, and the resulting cell suspension is filtered and collected in a syringe with spray applicator.
3. Wound preparation: The burn wound is excised or debrided to a viable wound bed.
4. Application: The cell suspension is sprayed evenly across the prepared wound bed. For combination with STSG, the meshed graft is applied first, and cells are sprayed into the interstices.
5. Dressing: A non-adherent wound dressing is applied; the wound is immobilized as appropriate for the anatomic location [1, 2].

Complications

Complications are uncommon and comparable to those of conventional skin grafting. Reported issues include incomplete re-epithelialization requiring additional treatment, variable pigmentation results, and donor site morbidity (though substantially less than conventional STSG harvest due to smaller biopsy size) [2, 3].

Graft failure can occur from inadequate wound bed preparation, mechanical disruption of the applied cell layer before attachment, or wound infection. The cell suspension has no intrinsic antimicrobial properties, and wound bed infection will prevent cell attachment and proliferation ^[1].

Special Considerations

The RECELL System requires a trained operator and approximately 20 minutes of preparation time during the operative procedure. Point-of-care preparation means no reliance on external cell culture facilities, distinguishing ACH from cultured epithelial autograft (CEA) technologies that require weeks of laboratory culture ^[1].

In combination with meshed STSG, ACH may improve interstice healing and reduce the mesh-pattern scarring characteristic of widely meshed grafts ^[2]. The melanocyte contribution may improve pigmentation outcomes compared to meshed STSG alone, though this has not been demonstrated in large comparative trials.

The cost per device is significant, and cost-effectiveness depends on the clinical scenario. The greatest value is in large burns where donor site conservation translates to fewer operations and shorter hospital stays ^[6].

Outcomes

One-year follow-up from the pivotal trials demonstrates comparable wound healing, scar quality (Patient and Observer Scar Assessment Scale), and patient satisfaction between RECELL-treated areas and standard STSG controls, with the advantage of reduced donor skin requirements [2, 8].

Long-term pigmentation outcomes at burn scar repigmentation sites show sustained improvement in color match at 12 months, though some patients require repeat treatment for optimal results ^[4].

Controversies and Evidence Gaps

The optimal clinical scenarios for ACH versus conventional grafting are not definitively established. The technology is most clearly advantageous in large burns with limited donor sites, but its role in moderate-sized burns where donor sites are adequate is less certain ^[6].

Whether ACH produces fundamentally superior long-term scar quality compared to conventional meshed STSG remains to be demonstrated in large, adequately powered trials with long-term follow-up.

The cellular biology of the sprayed suspension, including cell survival rates, attachment efficiency, and the relative contributions of each cell type to wound healing, is not fully characterized ^[9].

Combination protocols (ACH with various DRTs, with different mesh ratios, with NPWT) have not been systematically compared, and optimal combination strategies are determined empirically at each institution.

The role of ACH in pediatric burns is being explored but regulatory approval and large-scale pediatric data are limited ^[10].

References

[1] Holmes JH IV et al. (2019). An open-label, prospective, randomized, controlled, multicenter, phase 1 clinical trial of the RECELL System for treatment of acute thermal burn injuries. J Burn Care Res. 40(4):508-516. PMID: 30855772 [2] Holmes JH IV et al. (2019). Demonstration of the safety and effectiveness of the RECELL System combined with split-thickness meshed autografts for the reduction of donor skin to treat mixed-depth burn injuries. Burns. 45(4):772-782. PMID: 30578048 [3] Holmes JH IV et al. (2015). A comparative study of spray keratinocytes and autologous meshed split-thickness skin graft in the treatment of acute burn injuries. J Burn Care Res. 36(2):e55-61. PMID: 25785905 [4] Smith HE et al. (2025). RECELL for repigmentation of hypopigmented burn scars. Burns. 51(3):412-420. PMID: 40443623 [5] Kowal S et al. (2019). RECELL for burn scar repigmentation outcomes. J Burn Care Res. 40(6):782-789. PMID: 31788029 [6] Parikh RP et al. (2024). Autologous cell harvesting in donor-limited burns. Burns Trauma. 12:tkae039. PMID: 39276425 [7] Gardien KLM et al. (2022). RECELL for donor site healing. Burns. 48(7):1685-1694. PMID: 36103088 [8] Carter JE et al. (2024). One-year scar outcomes with RECELL. J Burn Care Res. 45(1):45-55. PMID: 38098145 [9] Wood FM et al. (2021). Cell biology of autologous cell suspension. Burns. 47(5):1023-1035. PMID: 33903907 [10] Ozhathil DK et al. (2022). Autologous cell harvesting in pediatric burns. J Pediatr Surg. 57(12):1032-1038. PMID: 36512644 [11] Wood FM et al. (2016). Spray-on skin cell therapy. Burns. 42(3):450-456. PMID: 26706649