. 2021 Jul 14;13(14):2319. doi: 10.3390/polym13142319

Table 4.

In vitro and in vivo studies of gelatin for skin wound healing.

Author	Objective	Study Design	Subject	Duration	Outcome	Conclusion
Lei et al., (2019) [93]	To study the effectiveness of self-healing gelatin	In vitro	L929 cellsand L02 cells	24 h and 72 h	‒ FTIR showed absorption band at 2 935 cm⁻¹ and amide I band at 1640 cm⁻¹. ‒ Healing effectiveness was at 50% at 40th and 90% at 60 min. ‒ Pore size ∼100 μm was seen. ‒ Equilibrium swelling ratio was ~1.28. ‒ The temperature at the maximum rate of weight loss 308.7 °C. ‒ Cell viability was >90% up to 72 h. ‒ Absence of cytotoxicity was recorded.	The fabricated self-healing gelatin has application prospects in biomedical fields.
Akhavan-Kharazian et al., (2019) [94]	To characterize gelatin as a potential agent for wound healing	In vitro	Human fibroblast cells	7 days	‒ FTIR showed absorption band at 3264 cm ⁻¹ (amide A), 1675 cm ⁻¹ (amide I), 1542 cm ⁻¹ and (amide II). ‒ Addition of chitosan increased the swelling percentage. ‒ The elastic modulus, tensile strength and elongation at break were 1450 ± 31 MPa, 47.3 ± 2.1 3 MPa and 5 ± 0.2 %. ‒ WVTR result was 46.1 g/m²/h. ‒ A 16 mm diameter of zone of inhibition was recorded against Escherichia Coli. ‒ Good adhesion of fibroblast cells and viability was seen up to 7 days.	Gelatin has the potential to be integrated as a wound healing material.
Hsu et al., (2019) [95]	To study the efficacy of gelatin for wound healing in diabetic mice	In vivo	Male C57BL/6 J Narl mice	Up to 10 days	‒ Porous structure was in the range of 20 µm to 300 µm. ‒ FTIR showed absorption bands at 1650 cm⁻¹ and 1545 cm⁻¹ for amide I and amide II, respectively. ‒ The degradation rate increased proportionally to the amount of collagenase. ‒ Thick granulation tissues, increased re-epithelization and blood vessel formation were observed in the treated group.	Gelatin is capable of contributing to diabetic wound healing.
Nikpasand et al., (2019) [96]	To access the outcome of gelatin nanocomposite in wound healing	In vivo	50 male rats	Up to 21 days	‒ Wound contraction was seen over time starting from day 6. ‒ Re-epithelization and neovascularization was seen in the experimental group. ‒ High level of mononuclear cells polymorphonuclear cells and proliferation of fibroblast cell was seen. ‒ Hydroxyproline content was recorded at 97.88 ± 3.77 mg g⁻¹ indicating a high level of Col deposition.	Gelatin nanocomposite accelerates wound healing.
Enrione et al., (2018) [103]	To study the efficacy of salmon gelatin in wound healing	In vivo	6 Orictholagus cuniculus rabbits	Not specified	‒ The pore size was 185.2 ± 27.1 µm ‒ Young modulus, stress at break and strain at break were 150.0 ±17.3 MPa, 316.8 ± 18.4 MPa and 2.48 ± 0.99%, respectively. ‒ DSC was recorded at 318.1 ± 0.5 K. ‒ Up to 93% of wound closure by week 4 was seen.	Salmon gelatin is a potential wound dressing material.
Garcia-Orue et al., (2019) [104]	To access the effectiveness of gelatin crosslinked with different agents for wound healing	In vitro and ex vivo assay	L-929 fibroblasts and redundant tissue from patients	Up to 8 days	‒ FTIR showed absorption bands at 1630 cm⁻¹, 1530 cm⁻¹, 1230 cm⁻¹ for amide I, amide II and amide III. ‒ At 700% swelling equilibrium was reached. ‒ WVTR existed in the range of 773.7 ± 43.4 g/m² day and 787.0 ± 50.9 g/m². ‒ Absence of cytotoxicity confirmed through CCK-8 assay. ‒ >70% of cell viability was recorded on day 4 and day 8. ‒ Increase in cell proliferation markers, myofibroblast differentiation, cytokeratin 14 and 10 was seen.	Gelatin hydrofilm serves as a perfect biomaterial for wound dressing.
Zeng et al., (2015) [105]	To access the effectiveness of gelatin microcryogel for wound healing	In vitro and In vivo	human adipose-derived stem cells and nude mice	Up to 11 days	‒ Pore size was 400 µm width and 500 µm height. ‒ Swelling ratio was recorded at 23.49 ± 1.57%. ‒ Yong modulus was recorded at 8.25 ± 0.64 KPa. ‒ >65% of adherence of cells to the scaffold with 1.5 h. ‒ Gene expression study showed increase in vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), basic fibroblast growth factor (bFGF) and platelet-derived growth factor (PDGF) at 48th hour.	Gelatin microcryogel supports wound healing.
Jang et al., (2017) [97]	To analyse the effectiveness of gelatin paste containing dermal powder for wound healing	In vitro and in vivo	Fibroblasts and Sprague Dawley rats	18th and 48th day	‒ On 18th day, 85% of wound contraction was seen in the gelatin group. ‒ A thick spinous layer and hyperkeratosis was seen on day 48. ‒ Low level of elastic fibers and blood vessel formation was seen in the controlled group. ‒ No significant immune response was seen. ‒ Leukocyte values were 7.28 ± 3.24 and 8.78 ± 2.71 for days 18 and 48, respectively.	Gelatin promotes full thickness wound healing.
Gomes et al., (2015) [106]	To evaluate the effectiveness of gelatin in skin wound healing	In vitro and in vivo	human fetal fibroblasts (HFFF2) and 18 Wistar rats	Up to week 4	‒ The porosity was recorded as 78 ± 10% with a lowest viscosity and highest conductivity. ‒ Gelatin scaffold was rigid with an elasticity result of 162 ± 96 MPa and brittle, ε = 9 ± 5%. ‒ FTIR showed 3280 cm⁻¹, 1640 cm⁻¹, 1530 cm⁻¹ and 1240 cm⁻¹ for amide A, amide I, amide II and amide III, respectively. ‒ Cell viability reduced to 67% on 2nd day of cell seeding. ‒ Continuous cell growth in gelatin scaffold was seen up to day 9. ‒ Cells were scattered in the gelatin scaffold which then improved in density and alignment by day 7. ‒ Rapid healing was recorded in in vivo study for gelatin group. ‒ Wound contraction, formation of new blood vessels and complete healing was achieved by week 4.	Gelatin scaffold supports full thickness wound healing.