Table 1.
Clinical applications of autologous keratinocytes, products based on autologous keratinocyte and autologous engineered skin in burns (NA—not available, CEA—cultured epithelial autograft, AT—active treatment, CT—control group, TBSA—total body surface area, CEA/A—cadaver allograft followed by placement of CEA onto an allodermis base, STSG—split-thickness skin graft, TESE—tissue-engineered skin equivalent, CSS—cultured skin substitutes).
| Therapy | Compared to | Route and Number of Administrations | Burn Characteristics | Follow Up | # of Patients | Age Range [Years] | Result | Author | Year |
|---|---|---|---|---|---|---|---|---|---|
| Autologous keratinocytes | |||||||||
| cultured epithelium | NA | grafts placed on a wound bed | major burns | NA | 2 | 5–6 | permanent epidermis generation | Gallico et al. [24] | 1984 |
| cultured autologous epidermis | NA | NA | second-and third-degree burn wounds | up to 4 years | 17 | NA | less hypertrophic scar formation | Teepe et al. [25] | 1990 |
| CEA | NA | NA | NA | NA | 104 | NA | final take rate of about 60% | Odessey et al. [26] | 1992 |
| cultured autologous keratinocytes | without graft | grafts | massive burns | NA | 64 (22–AT, 42–CT) | NA | mortality rate reduced from 48 to 14% | Munster et al. [27] | 1996 |
| sole-derived CEA | Axilla-; groin- or foreskin-derived CEA | grafts | full-thickness burn wounds or giant congenital nevi | 3,5 years | 12 | 0–17 | re-expression of K9 after grafting on muscle fascia | Compton et al. [28] | 1998 |
| CEA/CellSpray/ CEA + CellSpray | NA | application to the wound bed | burns > 50% TBSA | NA | 62 | 30–49 | reduction on surgical intervention and total length of stay in hospital | Wood et al. [21] | 2006 |
| CEA/A | NA | application to the wound bed | large burns | 3–90 months | 88 | 0.5–73 | the mean final take rate 72.7% | Sood et al. [22] | 2010 |
| CEA | NA | application to the wound bed | burns | NA | 63 | 2–70 | good outcome associated with young age and low number of infectious complications | Cirodde et al. [34] | 2011 |
| STSG + cultured autologous keratinocytes | cultured autologous keratinocytes alone, STSG alone | application to the wound bed | full-thickness skin burn, 55–65% TBSA | NA | 20 | 4–12 | accelerated wound closure, better esthetical results | Chrapusta et al. [30] | 2014 |
| CEA | non-CEA | mean 2,1 applications to the wound bed | burns; 60–80% of the TBSA | NA | 177 (CEA: 96; non-CEA: 81) | NA | improved survival | Kym et al. [33] | 2015 |
| CAE only and CAE after allogeneic cultured epidermis application | NA | grafts, in extensive burns in combination with large meshed STSG (1:6–1:12) | STSG donor sites and deep second-degree burns | NA | 63 | 0.75–58 | increased surface of the epidermal barrier | Auxefans et al. [29] | 2015 |
| CEA with a wide split auto mesh graft or patch graft | NA | 1 application | severe burns | NA | 5 | 13–28 | excellent epithelialization | Matsumura et al. [31] | 2016 |
| STSG + CEA | micrografting + CEA | grafts | severe burns | NA | STSG + CEA: 10; micrografting + CEA: 14 |
NA | significantly lower average area amount of skin used in the micrografting group | Chua et al. [35] | 2018 |
| CEA + widely meshed STSG (meshing ratio 1:3)/ Cuono method/ CEA only |
NA | an average of 8 sheets of CEA | burns ≥ 35% TBSA | 12 months | 12 (32 sites) | 22–67 | combination of STSG and CEA increases wound closure and improves CEA take rate | Lo et al. [36] | 2019 |
| CEA | NA | NA | burns | NA | 954 | <1–>80 | increased survival rate when combined with STSG | Hickerson et al. [37] | 2019 |
| Products based on autologous keratinocytes | |||||||||
| Epicel® | NA | grafts | burns | NA | 30 | 2.5–70 | very high beneficial value in the management of burns > 60% TBSA | Carsin et al. [39] | 2000 |
| ReCell® | skin grafts | spray | deep partial-thickness burns | 6 months | 82 (ReCell®–42, skin grafting–40) | NA | ReCell®gives similar results and is less invasive than skin grafting | Gravante et al. [44] | 2007 |
| Keraheal™ | NA | spray; combined with 1:4–6 mesh graft | extensive burns | 24 weeks | 29 | 30–49 | CEA’s take rate 100% after 4 weeks; enhanced take rate of a wide meshed autograft | Yim et al. [41] | 2011 |
| Keraheal™ | NA | spray; combined with 6:1 mesh graft when burn over 40% TBSA | full-thickness skin wound, TBSA 30–70% | up to 39 months | 16 | 18–70 | CEA’s take 68% after 4 weeks, 90.0% after 8 weeks | Lee et al. [13] | 2012 |
| Biobrane® with or without ReCell® | local standard treatment with surgery at 10 days | application to the wound bed | a pediatric partial-thickness scald injury | until 6 months post-burn | 13 (Biobrane® only-4; Biobrane® and ReCell® –5; CT –4) | Biobrane®only: 1.5–8.8; Biobrane® and ReCell®:0.8–1.8; CT: 2.5–7.1 | the best outcome when Biobrane® combined with ReCell®; decreased healing time, less pain, and better scar outcomes | Wood et al. [45] | 2012 |
| ReCell® | STSG | spray | partial-thickness burns | 52 weeks | 10 | NA | decreased donor site size, comparable outcomes with MSTSG treatment | Sood et al. [47] | 2015 |
| JACE® CEA | NA | grafts | burns > 30% TBSA | 52 weeks | 216 | 0–99 | increased survival rate | Matsumura et al. [50] | 2016 |
| JACE® CEA on meshed 3:1 split-thickness dermis graft or meshed 6:1 split-thickness autograft | NA | application to the wound bed | massive burns | NA | 3 | 51–66 | almost all of the burn wounds had healed at 6 weeks after surgery | Hayashi et al. [48] | 2018 |
| Autologous engineered skin | |||||||||
| cultured autologous keratinocytes and fibroblasts | NA | grafts | full-thickness burn wounds | 4 weeks | 4 | 20–53 | advance in the care of extensively burned patients | Hansbrough et al. [51] | 1989 |
| autologous TESE (cultured keratinocytes and fibroblasts) | NA | sheet | third-degree burn wounds | up to 9 months | 4 | 29–63 | appropriate for permanent repair of full-thickness skin defects | Takami et al. [53] | 2004 |
| CSS (autologous cultured keratinocytes and fibroblasts) | STSG | grafts, CSS were meshed at a ratio of 1:1.5 and applied weekly | full-thickness Burns | 2 to 7 years in 9 patients | 40 | 0.6–17 | better pigmentation, less scaring; no differences in qualitative outcomes after 1 year | Boyce et al. [52] | 2006 |