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Research group | Type of the study | ECM and loaded cells | Results | Remarks |
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Castagnoli et al. 2010 [57] | Noncomparative in vitro study | Human ADM + human keratinocytes | Preparation and characterization of a new cutaneous biosubstitute made up of alloplastic acellular glycerolized dermis & cultured autologous keratinocytes | (i) No in vivo studies (ii) Proof of principle |
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Han et al. 2010 [50] | Comparative in vivo study | Porcine ADM + autologous STSG +/− microencapsulated VEGF-expressing fibroblasts | Significant increase in survival & microvessels density in grafts containing microencapsulated VEGF-expressing cells | Cells were injected below the ADM and STSG |
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Eweida et al. 2011 [52] | Comparative in vivo study | Porcine UBM +/− rabbit keratinocytes | Reduction of early wound contraction and improving wound vascularity | (i) Keratinocytes were transplanted on the rough surface of the UBM (ii) No in vivo cell tracking |
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Liu et al. 2011 [14] | Comparative in vivo study | Mouse ADSC +/− porcine SIS +/− porcine ADM | Cell loaded ECM scaffolds showed better angiogenesis and early wound closure than cell-free ECM and cell loaded non-ECM scaffolds | The study emphasised the synergistic effect of ECM scaffolds and ADSC on angiogenesis |
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Lugo et al. 2011 [58] | Noncomparative in vivo study | Human ADM + human keratinocytes | The prevascularized neodermis supported the transplanted keratinocytes leading to a superior wound epithelialization | Keratinocytes were added in fibrin gel one week after implantation of the angiogenic factors-infiltrated ADM |
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Orbay et al. 2011 [37] | Comparative in vivo study | Rat ADM +/− rat ADSC | The construct enhanced the volume maintenance, vascular density, and collagen content in a subcutaneous soft tissue augmentation model in rats | The SC augmentation model did not address wound healing aspects related to epithelialization |
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Roessner et al. 2011 [15] | Comparative in vivo study | Human ADM (Epiflex) +/− rat fibroblasts +/− irradiation | Fibroblasts added no significant difference regarding soft tissue volume regeneration. However, a significant increase in wound tensile strength was noted if the transplanted cells were not subjected to irradiation | (i) The ADM was implanted within a deeper tissue defect to replace excised muscles (ii) Due to this special defect design, the increase in wound breaking strength may not be directly related to the physical presence of the seeded implants |
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Seland et al. 2011 [40] | Comparative in vivo study | Human ADM +/− human keratinocytes (loaded on microcarriers or as single layer or as STSG) | Only the keratinocytes implanted as STSG or loaded on microcarriers had a significant positive effect on epidermal and dermal thickness at 16 & 21 days after transplantation | (i) Keratinocytes were added to the fibrin pretreated wounds fourteen days after the initial transplantation of ADM (ii) In vivo tracking of transplanted cells was performed till the end of the experiment |
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Huang et al. 2012 [51] | Comparative in vivo study | Mouse ADM +/− human ADSCs | Increased thickness of granulation tissue, improved reepithelialization & wound closure rate, and increased vascular density | (i) ADSCs were seeded on ADM and not directly to the wound bed (ii) In vivo cell tracking was performed till day 14 (iii) VEGF-expressing ASCs could be detected after transplantation |
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Peramo et al. 2012 [39] | Noncomparative in vitro study | Human ADM (Alloderm) + human keratinocytes (from skin and oral mucosa origins) | In vitro development of human mucocutaneous lip junction equivalent | (i) In vitro proof of principle and was not examined in vivo (ii) Maintaining this delicate transition zone would be challenging in a normal surgical setting |
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Shi et al. 2012 [16] | Noncomparative in vitro study | SIS + human keratinocytes in a high MMP medium | SIS inhibits the MMP activity and thus promotes keratinocyte migration | The study focuses on the role of the bioactive structure of SIS rather than its scaffolding properties |
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Zajicek et al. 2012 [38] | Noncomparative in vitro study | Porcine ADM (Xe-Derma) + human keratinocytes | The results suggest that the firm natural structure of ADM stimulates proliferation and differentiation of human primary keratinocytes | A concomitant in vivo study involved the application of only the scaffold without adding cells in acute wounds |
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Deshpande et al. 2013 [44] | Comparative in vitro study | Human ADM + keratinocytes +/− fibroblasts +/− basement membrane | The formation of a well-organized epithelium depends on the presence of intact basement membrane but is independent of the presence of cultured fibroblasts | Exclusively in vitro study |
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Huang et al. 2013 [59] | Comparative in vivo study | Human keratinocytes +/− cross-linked human acellular amniotic membrane | Combination of keratinocytes with the acellular amniotic membrane significantly reduced wound contraction at 4 weeks than the cells alone | The study did not include a group with the ECM alone |
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Lam et al. 2013 [31] | Comparative in vivo study | +/− mouse ADSC +/− porcine SIS | (i) In vivo cell tracking revealed a significant increase in stem cell survival and proliferation with SIS (ii) Delivering stem cells on the SIS significantly decreased fibrosis but slightly improved healing, while SIS alone hindered healing as the patch stented the wound open | (i) A splinted excisional wound model was used to simulate human wound healing and minimize healing by contracture (ii) The special splint-wound design and the too early removal of the SIS patch in some groups (2 days) led to unfavorable results in terms of wound healing |
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Sahin et al. 2013 [48] | Comparative in vivo study | Human ADM +/− rat bMSCs | Increased, adherence, angiogenesis, and vertical vascular penetration of ADM especially if combined with negative pressure dressing therapy | (i) The MSCs were added once & randomly to the wound bed before ADM implantation (ii) The bMSCs were not tracked in vivo (iii) The early adherence of ADM was probably related to early angiogenesis |
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Yeum et al. 2013 [30] | Comparative in vivo study | SIS +/− mouse bMSCs | Enhanced wound closure and less wound inflammation with bMSCs | (i) bMSCs were repeatedly transplanted every 2 days for 2 weeks (ii) In vivo cell tracking was performed |
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Bondioli et al. 2014 [60] | Comparative in vitro study | Fibroblasts +/− human ADM | The matrix extract significantly increased the proliferation rate of fibroblasts | Only an in vitro study as part of the characterization of the matrix |
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