Table 2.
Studies on CS-based scaffolds for cutaneous tissue regeneration.
| Authors | Scaffold type | Study outline | Results | Conclusion |
|---|---|---|---|---|
| Guo et al. 2011 [63] |
Bilayer CS (DA 15–25%; MW: 100–170 kDa) +COL membranes (ratio NA) impregnated or not with TMC (DD 90%) and VEGF (plasmid-DNA encoded) | In vitro: CC in HUVEC culture In vivo: implantation of membranes on burn skin lesions on the backs of guinea pigs. HT, PCR, and Western-blot analyses Control groups: blank scaffolds and CS/COL/TMC/pDNA without VEGF Sample: not specified |
Greater cell viability and VEGF expression in scaffolds with TMC/pDNA-VEGF than the controls in vitro Greater angiogenesis, VEGF expression and better repair of wounds with TMC/pDNA-VEGF scaffolds in vivo |
CS+COL impregnated with TMC and VEGF promoted angiogenesis and dermal regeneration (P < 0.05), showing potential for use in the regeneration of epithelial lesions |
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| Tchemtchoua et al. 2011 [64] | Films, sponges, and CS nanofibrils (DA 16% and MW 67 kDa) | In vitro: CC in a culture of fibroblasts, keratinocytes, and endothelial cells In vivo: implantation in the subcutaneous tissue (back skin) of 10-week-old mice (biocompatibility) and in skin defects; HT evaluation Control: untreated defects Sample: n = 10 |
In vitro: greater adhesion, cell proliferation, and differentiation with nanofibrillar CS In vivo: greater biocompatibility and faster regeneration of wounds with nanofibrillar CS; CS sponges caused foreign body reaction |
The authors conclude that the nanofibrillar form has advantages over the others, being more biocompatible and effective in regeneration of the skin |
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| Sundaramurthi et al. 2012 [65] | CS (DA 15%; MW: NA) in nanofibrils or films (crosslinked with glutaraldehyde), in combination with PVA and RSPO1 (50 ng) | In vitro: CC in fibroblast cell culture; evaluation by RT-PCR In vivo: implantation on skin wounds on rats' backs; macroscopic and HT evaluation Control groups: untreated wounds (negative), Bactigras® (positive) Sample: n = 3 |
In vitro: greater cell adhesion and proliferation in nanofibrillar CS+PVA group (P < 0.05) In vivo: complete macroscopic regeneration after 2 weeks and better histopathological results in the CS+PVA+RSPO1 group (P < 0.05) |
CS+PVA demonstrated good results as carrier of the growth factor, constituting a biocompatible biomaterial with potential for application as a skin substitute |
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| Veleirinho et al. 2012 [66] | CS (medium MW; DA: NA) combined with the polymer PHBV (ratios: 2 : 3 and 1 : 4) | In vitro: CC in a culture of fibroblast cells of mouse; In vivo: implantation of scaffolds and a commercial biomaterial as a control in skin wounds on the backs of 2-month-old rats; macroscopic and HT evaluation of regeneration. Sample: not specified |
In vitro: cell viability and proliferation with CS+PHBV (1 : 4) similar to the control (P > 0.05) In vivo: greater organization and maturation of the epithelial tissue with CS+PHBV (1 : 4); lower occurrence of inflammatory infiltrate with CS+PHBV (2 : 3) |
CS+PHBV has potential for promoting skin regeneration, with biocompatibility in vitro |
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| Wang et al. 2013 [67] | CS membranes (MW 100 to 171 kDa; DA 15%) + COL and PLGA (ratio: NA) | In vivo: implantation of the scaffolds, with or without PLGA, on skin defects in backs of 2-month-old rats; macroscopic, HT, IHC, PCE analyses and tensile strength tests. Sample: n = 12 |
CS+COL+PLGA scaffolds demonstrated better healing and greater expression of IHC and PCR markers and higher mechanical performance (P < 0.05) | CS+COL scaffolds reinforced with PLGA demonstrated acceleration of angiogenesis and better skin regeneration than CS+COL (P < 0.05) |
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| Sarkar et al. 2013 [68] | Crosslinked CS membranes (MW 71 kDa; DA < 10%) whether or not combined with COL | In vitro: CC in culture of fibroblasts and keratinocytes. In vivo: implantation in human skin defects ex vivo; HT analyses. Control groups: not specified Sample: n = 3 |
In vitro: CS+COL demonstrated better cell adhesion, proliferation, and viability In vivo: CS+COL promoted partial reepithelialization with migration after 14 days; pure CS did not promote regeneration |
CS+COL scaffold promoted better regeneration of skin wounds than pure CS scaffolds (P < 0.05) |
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| Zeinali et al. 2014 [24] | CS membranes (medium MW; DA 15–25%) crosslinked with PHBV, with or without SC (2 × 106) | In vitro: CC in umbilical cord SC culture; In vivo: implantation in skin defects on 4–8-week-old rats' backs; HT and IHC analyses. Control not specified. Sample: n = 10 |
In vitro: CS+PHBV showed greater cell proliferation and viability In vivo: greater regeneration of cutaneous tissue with CS+PHBV+SC Statistical analysis not performed |
CS+PHBV added to stem cells was capable of regenerating full thickness skin defects in rats |
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| Guo et al. 2014 [69] | Bilayer CS (MW 100–170 kDa; DA 15–25%) +COL and silicone membranes (ratio: NA) |
In vivo: implantation of scaffolds in excisional or burnt skin lesions in guinea pigs; HT, IHC and IF evaluations; c Control group: commercial bandage; sample: n = 2 |
CS+COL produced results inferior to the control in the regeneration of burn lesions (P < 0.05) There was no significant difference with excisional lesions (P > 0.05) | CS and collagen demonstrated effectiveness similar to the commercial product in the regeneration of skin damaged by excisional wounds |
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| Revi et al. 2014 [29] | CS sponges (MW 354 kDa; DA 14%) impregnated or not with keratinocytes and fibroblasts |
In vivo: implantation of scaffolds or unspecified commercial product (positive control) in dorsal skin lesions of rabbits; HT and IHC analyses; no negative control. Sample: n = 6 |
CS scaffolds with or without cells exhibited slower complete reepithelization of lesions (28 days) than commercial product (14 days) (P = 0.02 compared to CS without cells and P = 0.03 compared to CS with cells) |
CS sponges combined with dermal cells showed potential for application in the regeneration of complete skin defects |
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| Han et al. 2014 [27] | CS sponges + GEL (ratio NA) incorporated with antibacterial drugs. MW and DA not reported. Drugs not reported |
In vitro: CC in culture of skin fibroblasts); porosity, water absorption and biodegradation tests; In vivo: implantation of scaffolds in skin lesions on rabbits' backs; HT analysis of biocompatibility; no negative control. Sample: n = 4 |
In vitro: CS+GEL demonstrated adequate CC In vivo: inflammatory infiltrate present within 15 days, being lower in sponges with antimicrobials; there was no lesion regeneration Statistical analysis was not performed |
CS+GEL exhibited adequate physicochemical properties and cytocompatibility in vitro, but induced inflammation in vivo |
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| Ahamed et al. 2015 [70] | CS+ cellulose (ratio NA), incorporated with nanoparticles of silver, with or without gentamicin. MW and DA not reported |
In vivo: implantation in skin lesions in the backs of Wistar rats; macroscopic, biochemical and planimetric analyses. Controls: sterile cotton gauze dipped with gentamicin or standard soframycin ointment. Sample: n = 3 |
Scaffolds with or without gentamicin did not exhibit any difference between one another but were better than controls The healing was complete after 25 days P not reported |
CS + cellulose was effective in the regeneration of skin wounds |
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| Wang et al. 2016 [71] | COL+CS (DA < 15%; MW 106–171 kDa) + PLGA + PUR (ratio NA) | In vivo: implantation in skin lesions on the backs of 2-month-old Sprague-Dawley rats; SEM, HT and IHC analyses; tensile strength tests; Control groups; commercial membrane (COL + silicon); Sample: n = 12 |
COL+CS+PLGA+PUR showed greater expression of angiogenesis markers, better regeneration of cutaneous tissue wounds and better mechanical performance than commercial membrane used as control | COL+CS+PLGA+PUR membranes promoted better regeneration of skin defects in comparison with commercial membrane (P < 0.05) |
CC: cytocompatibility; COL: collagen; CS: chitosan; DA: degree of acetylation; HT: histological; IHC: immunohistochemical; kDa: kilodaltons; MW: molecular weight; PCE: polycaprolactone-polyethylene glycol polymer; PHBV: poly(3-hydroxybutyrate-co-3-hydroxyvalerate; PLGA: polylactic-co-glycolic acid; PUR: polyurethane; PVA: polyvinyl-alcohol; RT-PCR: real time-polymerase chain reaction; RSPO1: R-spondin-1 angiogenesis growth factor; TMC: trimethyl chitosan chloride; VEGF: vascular endothelial growth factor.