TABLE 5.
Application of perinatal tissue extract alone or compared to/combined with with perinatal tissue or cells of non-perinatal origin in in vivo animal models of skin wound healing. Time points indicated in the “Dosage” and “Outcome” column mean days (d) or weeks (w) of/after treatment.
| Perinatal tissue extracts | |||||
|---|---|---|---|---|---|
| PnD | Dosage | Application (carrier) | Wound type, animal | Outcome | References |
| hAM extract | 83.3 μg extract/cm2 | a) Topical | Burn 1st degree, rat | hAM+chitosan-gel increased cutaneous regeneration (granulation tissue, fibroblast proliferation, vascularization) compared to controls (PBS, gel) (d15, d25, d31). High concentrated hAM extract (1 mg/ml) achieved better effects than low concentrated hAM extract (0.1 mg/ml) | Momeni et al. (2018) |
| 8.33 μg extract/cm2 | b) Topical (chitosan hydrogel) | ||||
| hAM extract | 100 μg/ml wound dressing (applied volume not spec.) | Topical (PVA/SA gel) | Full-thickness, rat | hAM+PVA/SA-gel accelerated wound closure, increased re-epithelization, granulation tissue areas, neovascularization, collagen proliferation and reduced number of inflammatory cells compared to Medifoam™ hydrogel or the control (sterile gauze) (d6, d9, d12) | Choi et al. (2014) |
| hP extract | 3.98 µl extract/cm2 | Subcutaneous injection | Full-thickness, mouse | hP extract accelerated wound healing (d3-d9) TGF-β increased in the early phase of wound healing (d6) and VEGF in the late phase (d14) compared to PBS control | Hong et al. (2010) |
| 3.33 μl extract/cm2/d | Subcutaneous injection or Intraperitoneal injection | Skin flap, rat | hP extract enhanced flap survival, angiogenesis, reduced necrotic areas, induced antioxidative response and inhibited apoptosis compared to PBS control. Daily application (d0-d6) of low dose localized or systemic hP injections or high dose. Systemic high dose HP injections showed the best effects. (d7) | Kwon et al. (2019) | |
| 0.45 and 1.35 ml/kg/d every day for 7 days | |||||
| a) hP extract | a) 35 μg/cm2 | Subcutaneous injection | Full-thickness, rat | hP and placental laminin accelerated wound closure compared to PBS controls (d5, d7, d9) | Mukherjee et al. (2020) |
| b) Placental laminin | b) 11 μg/cm2 | ||||
| a) hAM powder | 2 μg hAM/cm2 | Topical | Burn 2nd degree, rat | hAM powder, AV, and hAM+AV accelerated wound healing compared to untreated wounds (d24) | Rahman et al. (2019) |
| b) hAM powder+AV | 1 μg hAM + 1 μg AV/cm2 | ||||
| Solubilized hAM | Not specified | Topical (hyaluronic acid hydrogel) | Full-thickness, mouse | hAM-hyaluronic acid hydrogel accelerated wound closure, wound re-epithelialization, vascularization compared to controls (hydrogel, untreated). Hydrogel ± hAM counteracted wound contracture in contrast to untreated wounds (d7, d14) | Murphy et al. (2017) |
| hP–ECM | Not specified | Topical (hybrid with silk fibroin) | Full-thickness, rat | hP-ECM-silk fibroin scaffolds accelerated wound closure (pronounced angiogenesis, enhanced granulation tissue formation, early re-epithelialization) compared to controls (collagen-silk-fibroin scaffolds, sham) (d7, d14, d21) | Rameshbabu et al. (2018) |
| hWJ-ECM | 450 μl/cm2 | Topical (hWJ-ECM scaffold) | Full-thickness, mouse | WJ-ECM scaffolds accelerated wound closing and re-epithelization compared to wounds without scaffolds (d7, d12) and counteract wound contracture (d18) | Beiki et al. (2017) |
| hWJ-ECM | 353.7 μl/cm2 | Topical (Matrigel) | Full-thickness, mouse | Acellular hUC-WJ+Matrigel enhanced wound closure and augmented the differentiation of fibroblasts into myofibroblasts compared to control (DMEM-Matrigel) (d5, d7) | Bakhtyar et al. (2017) |
| Perinatal tissue extracts compared to perinatal tissue | |||||
| PnD | Dosage | Application (carrier) | Wound type, animal | Outcome | References |
| a) hAM powder | Not specified | Topical | Full-thickness, pig | Amnion+hydrogel and amnion powder accelerated wound healing compared to AmniograftR > hydrogel only > untreated wounds > graft jacket. The treatment with graft jacket-only led to the worst healing (most wound, most contraction, least epithelialization (d28) | Murphy et al. (2020) |
| b) hAM powder+hydrogel | |||||
| c) AmniograftR | |||||
| Perinatal tissue extracts combined with cells of non-perinatal origin | |||||
| PnD | Dosage | Application (carrier) | Wound type, animal | Outcome | References |
| a) hPE+autologous BM-MSC | Concentration of hPE not specified (commercial preparation) 1 × 10^6 cells/cm2 | Topical | Full-thickness, rabbit | hP-E+ BMSC achieved better results on wound healing (accelerated wound closure, earlier disappearance of inflammatory reaction, better epithelialization, neovascularisation, and collagen formation than the other groups (d7, d14, d21, d30) | Akela et al. (2013) |
| b) hPE+buffy coat in autologous plasma) | |||||
| c) hPE+autologous plasma | |||||
Abbreviations: AV, aloe vera; BM-MSC, bone marrow mesenchymal stromal cells; hAM, human amniotic membrane; hPE, human placenta extract; hP-ECM, human placenta extracellular matrix; hUC-WJ-ECM, human umbilical cord Wharton´s jelly extracellular matrix; PVA, polyvinyl alcohol; SA, sodium alginate.