Clinical, histological and homeostasis evaluation of an autologous tissue bio-engineered skin substitute in a patient with 70% of total body surface area (TBSA) burn

Fernández-González, A.; Lizana-Moreno, A.; Fernández, N.; Guerrero-Calvo, J; Ruiz-Garcia, A.; Espinosa, Olga; Ordóñez-Luque, A.; Sierra-Sánchez, Álvaro; Arias‐Santiago, Salvador

doi:10.1016/j.jcyt.2017.02.339

Cited by 7 publications

(12 citation statements)

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“…Two types of TESSs, changing the biomaterial (hyaluronic acid and agarose), were elaborated replicating, on a lower scale, the GMP manufacturing process established in our laboratory for TESSs used in severe burn patients 8 . To that purpose, two mixes with different components (Table , Supporting Information) were blended until achieving a final volume of 5 mL per construct (wells of 2.4 cm of diameter).…”

Section: Methodsmentioning

confidence: 99%

“…Our group has scaled up a human tissue‐engineered skin substitute (hTESSs), based on fibrin–agarose hydrogel 7 in a Good Manufacturing Practice (GMP) facility with acceptable clinical results in the treatment of severe burn patients 8 . However, agarose is difficult to manipulate under GMP conditions (need to be heated to 37°C) and has not human origin.…”

Section: Introductionmentioning

confidence: 99%

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Hyaluronic acid biomaterial for human tissue‐engineered skin substitutes: Preclinical comparative in vivo study of wound healing

Sierra-Sánchez

Fernández-González

Lizana-Moreno

et al. 2020

Acad Dermatol Venereol

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Background There is not an ideal biomaterial for tissue-engineered skin substitutes (TESSs), and most of the studies or existing therapies use xenogeneic origin natural biomaterials or biosynthetic scaffolds. Objective To analyse clinical, histological integration and homeostasis parameters of a human TESS manufactured with fibrin-hyaluronic acid biomaterial (HA-Skin), grafted in immunodeficient mice for 8 weeks, and compared with the gold standard treatment (Autograft), a human TESS manufactured with fibrin-agarose biomaterial (AG-Skin) and secondary wound healing dressings. Methods Human TESSs and autografts were implanted into BALB/c mice after surgical excision. Secondary wound healing approach was achieved with biosynthetic collagen wound dressing (Biobrane â) and fibrin-hyaluronic acid or fibrin-agarose biomaterial without cells (Total N = 44). Clinical integration and homeostasis parameters were evaluated every two weeks for two months. Histological and immunohistochemical analyses were performed four and eight weeks after grafting. Results HA-Skin, AG-Skin and Autograft groups showed a proper clinical integration and epithelization eight weeks later. Scar evaluation revealed better results for Autograft and HA-Skin. Homeostasis analysis indicated similar values of transepidermal water loss and elasticity between HA-Skin (6.42 AE 0.75 g/h/m 2 , 0.42 AE 0.08 AU), Autograft (6.91 AE 1.28 g/h/m 2 , 0.40 AE 0.08 AU) and healthy mouse skin (6.40 AE 0.43 g/h/m 2 , 0.35 AE 0.03 AU). Histological results showed that human TESSs and autografts presented better skin structuration and higher expression of cytokeratins. Conclusions This study suggests that human TESS based on fibrin-hyaluronic acid biomaterial could be suitable for clinical application in the treatment of several dermatological pathologies (wound healing).

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid biomaterial for human tissue‐engineered skin substitutes: Preclinical comparative in vivo study of wound healing

Sierra-Sánchez

Fernández-González

Lizana-Moreno

et al. 2020

Acad Dermatol Venereol

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“…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 ...…”

Section: Human Adult Skin Cells In Tesssmentioning

confidence: 97%

“…Remaining studies indicated the beneficial role of using CSSs alone 89 , 96 , 98 – 100 , 103 or combined with autografts 86 , 87 , 91 , 94 , 97 , 101 for the treatment of deep and difficult to heal injuries, evaluating different parameters such as graft take, histological appearance of new skin and cosmetic and functional outcomes.…”

Section: Human Adult Skin Cells In Tesssmentioning

confidence: 99%

“…Regarding to the biomaterials used for the fabrication of the scaffolds, different types of collagen 87 , 90 , 93 , 95 , 101 , 106 or combined with glycosaminoglycan 86 , 88 , 89 , 91 , 92 , 104 were the preferred sources, although different formulations of plasma/fibrin were also reported 94 , 96 , 98 , 102 , 103 . Finally, hyaluronic acid 97 or acellular dermal matrices derived from human fibroblasts 99 , 100 , 105 were evaluated too.…”

Section: Human Adult Skin Cells In Tesssmentioning

confidence: 99%

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Cellular human tissue-engineered skin substitutes investigated for deep and difficult to heal injuries

et al. 2021

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Wound healing is an important function of skin; however, after significant skin injury (burns) or in certain dermatological pathologies (chronic wounds), this important process can be deregulated or lost, resulting in severe complications. To avoid these, studies have focused on developing tissue-engineered skin substitutes (TESSs), which attempt to replace and regenerate the damaged skin. Autologous cultured epithelial substitutes (CESs) constituted of keratinocytes, allogeneic cultured dermal substitutes (CDSs) composed of biomaterials and fibroblasts and autologous composite skin substitutes (CSSs) comprised of biomaterials, keratinocytes and fibroblasts, have been the most studied clinical TESSs, reporting positive results for different pathological conditions. However, researchers’ purpose is to develop TESSs that resemble in a better way the human skin and its wound healing process. For this reason, they have also evaluated at preclinical level the incorporation of other human cell types such as melanocytes, Merkel and Langerhans cells, skin stem cells (SSCs), induced pluripotent stem cells (iPSCs) or mesenchymal stem cells (MSCs). Among these, MSCs have been also reported in clinical studies with hopeful results. Future perspectives in the field of human-TESSs are focused on improving in vivo animal models, incorporating immune cells, designing specific niches inside the biomaterials to increase stem cell potential and developing three-dimensional bioprinting strategies, with the final purpose of increasing patient’s health care. In this review we summarize the use of different human cell populations for preclinical and clinical TESSs under research, remarking their strengths and limitations and discuss the future perspectives, which could be useful for wound healing purposes.

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Hierarchical double-layer microneedles accomplish multicenter skin regeneration in diabetic full-thickness wounds

Huang,

Niu,

et al. 2024

Journal of Advanced Research

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Clinical, histological and homeostasis evaluation of an autologous tissue bio-engineered skin substitute in a patient with 70% of total body surface area (TBSA) burn

Cited by 7 publications

References 0 publications

Hyaluronic acid biomaterial for human tissue‐engineered skin substitutes: Preclinical comparative in vivo study of wound healing

Hyaluronic acid biomaterial for human tissue‐engineered skin substitutes: Preclinical comparative in vivo study of wound healing

Cellular human tissue-engineered skin substitutes investigated for deep and difficult to heal injuries

Hierarchical double-layer microneedles accomplish multicenter skin regeneration in diabetic full-thickness wounds

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