Table 4.
Clinical use of human composite skin substitutes (CSSs).
| References | Cells | Type of clinical study | n (male/ female) | Age (years)a | Treatment-related adverse events | Indication | Total body surface area (TBSA) affected (%)a | Affected area covered (%)a or Affected area covered (%TBSA)a | TESS successful engraftment (%)a or TESS successful engraftment (% TBSA)a | Period between skin biopsy and grafting (days)a | Follow-up (months)a | Outcomes |
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| 86 | Autologous keratinocytes and fibroblasts | Case Report | 4 (3/1) | 33.5 ± 15.5 (20–53) | None | Burns | 51.5 ± 15.4 (40–74) | – | 69.2 | 21.2 ± 3.5 (19–28) | 1 | There was an improved quality of skin healed with cultured cells |
| 87 | Autologous keratinocytes and fibroblasts | Case Report | 2 (2/0) | 40.5 ± 14.8 (30–51) | None | Burns (1) | 81 | 100 | – | 21 | 10 | Mature epidermis and well-differentiated papillary and reticular dermis were formed |
| Excised wounds (1) | – | 100 | 100 | |||||||||
| 88 | Autologous keratinocytes and fibroblasts | Prospective Randomized Clinical Study | 17 | 12.7 ± 3.3 (1–50) | Increased incidence of exudates | Burns | 68.8 ± 2.4 (51–87) | – |
0 (5 patients) 50–90 (12 patients) |
25.3 ± 9.3 | 12 | Pigmentation was greater, scar was less raised, but regrafting was more frequent in skin substitutes compared with split-thickness autografts |
| 89 | Autologous keratinocytes and fibroblasts | Case Report | 5 (4/1) | 15.6 (4–38) | None | Burns | 77.8 (58–87) | – | 100 | >14 | 6 | Connection between epidermis and connective tissue, together with spontaneous repigmentation was observed |
| 90 | Allogeneic keratinocytes and fibroblasts | Prospective Randomized Compared Clinical Study | 11 | – | None | Surgical wounds | – | – | 90 | – | 2 | Rapid healing and reduction of the pain |
| 91 | Autologous keratinocytes and fibroblasts | Case Report | 3 (3/0) | 4.33 (2–7) | None | Burns | 72 (63–88) | 12.8 (8.4–21.3) | 100 | 21 | 2 | Stable epithelium covered a layer of newly formed fibrovascular tissue. Smooth, pliable, and hypopigmented skin |
| 92 | Autologous keratinocytes and fibroblasts | Prospective, Randomized, Non-blinded Clinical Study | 45 (34/11) | 10.6 ± 1.6 | None | Burns | 64.6 ± 2 | 16.7 ± 2.6 | 95.4 ± 1.8 | 28 | 12 ± 1 | Healed skin was soft, smooth, and strong with irregular pigmentation. Impact of TESS on wound closure increases proportionately with the magnitude of the wound area |
| 93 | Allogeneic keratinocytes and fibroblasts | Case Report | 3 (2/1) | 36.3 ± 14.9 | Local inflammation | Burns | <20 | – | 23.5 ± 10.7 | 17–24 | 0.25 | By 1 week after grafting there remained a few islands of keratinocytes on an inflamed bed |
| 94 | Autologous keratinocytes and fibroblasts | Case Report | 2 (2/0) | 22.5 (17–28) | None | Burns | 67.5 (50–85) | – | 100 | 24.6 (23–26) | 24 | Epidermal regeneration was stable, with good cosmetic outcome |
| 95 | Autologous keratinocytes and fibroblasts | Randomized Controlled Trial | 40 | - | None | Burns | 73.4 | – | 81.5 ± 2.1 | – | 12 | Vancouver Scale Scores were not different for erythema, pliability, or scar height, but pigmentation remained deficient against autograft treatment |
| 96 | Autologous keratinocytes and fibroblasts | Case Series | 20 | 22.9 ± 16.3 (6–62) | None |
Burns (13) Giant nevus (5) Graft-vs.-host disease (1) Neurofibromatosis (1) |
– | – |
Burns: 56.9 ± 25.3 (10–90) Giant nervus: 82 ± 7.6 (70–90) Graft-vs.-host disease: 90 Neurofibromatosis: 75 |
25 | 1–18 | Epithelization obtained was permanent |
| 97 (NCT00718978) | Autologous keratinocytes, melanocytes and fibroblasts | Single Group Assignment Open-Label Clinical Trial | 11 (3/8) | 24.6 (2–57) | None |
Giant nevus (5) Tumors (2) Scars (3) Trauma (1) |
– | – | 30–95 | 30 | 36 | Loss of the epithelial layer varied markedly (from 5 to 70%) while fibroblast cellular component growth prevailed |
| 98 | Autologous keratinocytes and fibroblasts | Multicenter Retrospective Observational Cohort Study | 25 (23/2) | 29 ± 11 (9–58) | Thirteen patients presented wound infection (P. aeruginosa mainly) | Burns | 74 ± 17 (35–100) | 24 ± 13 (7–60) | 49 ± 30 (0–100) | 23 ± 5 (12–28) | 45 ± 27 (2–91) | Characteristic scarring of mesh interstices was avoided. Epithelialization was observed |
| 99 | Autologous keratinocytes and fibroblasts | Prospective Uncontrolled Case Study | 5 (1/4) | 55.2 ± 18.5 (26–74) | None | Skin ulcers | – | 100 | 100 | 52–63 | 6–19 | Effective treatment of long-standing hard-to-heal venous or mixed ulcers |
| 100 | Autologous keratinocytes and fibroblasts | Case Report | 4 (1/3) | 42.3 ± 14.7 (29–63) | None | Burns | 64.8 ± 26.9 (40–98) | – | 94.8 ± 4.3 (90–100) | 21 | 1–9 | Dermal part had a well-vascularized dermal matrix and bilayer structure was conserved |
| 101 | Autologous keratinocytes and fibroblasts | Case Report | 1 (1/0) | 48 | None | Burns | 40 | – | 88 | 19 | 1 | CSS completely covered the wound area and smoothly adapted to the wound ground. Color resemblance of the transplant to the healthy skin increased through the follow-up period |
| 102 | Autologous keratinocytes and fibroblasts | Case Report | 2 | 9.5 ± 6.3 (4–14) | None | Burns | 80 ± 21.2 (65–95) | – | – | – | 36 | Appearance of the skin did not differ significantly from the areas treated with autografts |
| 103 | Autologous keratinocytes and fibroblasts | Case Report | 1 (0/1) | 29 | None | Burns | 70 | 100 | 100 | 28 | 6 | Patient was discharged after 163 days of hospital admission with a complete skin coverage, correct functioning of the four limbs and autonomous walking |
| 104 (NCT00591513) | Autologous keratinocytes and fibroblasts | Prospective Randomized Open-Label Paired-Site Comparison Clinical Trial | 16 (14/2) | 6.3 ± 1.1 (1.4–17.5) | None | Burns | 79.1 ± 2.2 (59.5–95.9) | 33.4 ± 3.5 (9.7–71.6) | 83.5 ± 2.0 | 32.1 ± 1.1 (24–42) | 12 | Vascularization of the dermal component occurred during the first week after grafting, and CSS stabilized barrier function, basement membrane, and nutrient supply were restored |
| 105 | Autologous keratinocytes and fibroblasts | Case Series | 14 (12/2) | 34 ± 16 (10–63) | None | Burns | 74 ± 13 (52–92) | 19±15 (3–53) | 98 ± 5 (85–100) | 62.7 ± 4.8 (56–71) | 38 ± 23 | No loss of the epithelium was observed during the first-year post-intervention or reported subsequently. Grafted TESSs expanded when the patient grew or gained weight. |
| 106 | Autologous keratinocytes and fibroblasts | Phase I Two-armed, Open-Label Prospective Clinical Trial | 10 (6/4) | 9 ± 4 (7–14) | Four cases of hematoma | Burns (1) Reconstructive surgery for burn scars (9) | – | 100 | 67 ± 32 (0–100) | 32 ± 4 (26–38) | 15 ± 7 (2–25) | Three months postoperatively, there was a multilayered, well-stratified epidermis and a dermal compartment comparable to native skin |
aExpression of measures: mean ± standard deviation (range).