Advancing burn wound treatment: exploring hydrogel as a transdermal drug delivery system

Figures & data

Table 1. Classification of burn by depth.

Burn degree/thickness		Depth	Treatment	Healing time
First (superficial)		Superficial epidermis	- Cool water irrigation - Application of burn creams or ointment	With minimal scarring in about a week
Second	superficial-partial thickness	Epidermis and superficial of dermis	- Use of topical antimicrobial creams or dressings to prevent infection	With minimal scarring, < 3 weeks if there is no wound infection
	deep-partial thickness	Epidermis and deep dermis	- Use of topical antimicrobial creams or dressings to prevent infection - Surgical intervention may be necessary	Possibility of scarring, 3–5 weeks
Third (full thickness)		Epidermis, dermis, and hypodermis (subcutaneous tissue)	- Surgical intervention, including excision and skin grafting - Temporary coverage with dressing /skin substitute	Scarring, >8 weeks
Fourth (full thickness)		Beyond the full thickness of the skin to involve muscles and bones	- Surgical intervention, often including excision, debridement, reconstruction, and grafting	Scarring, >8 weeks

Figure 1. Characteristics of an ideal burn wound dressing.

Figure 2. Properties of hydrogel as a potential wound dressing for burn wound healing. Reprinted from an open-access source (Negut et al., 2018).

Figure 3. Therapeutic agents-incorporated hydrogels that improve their versatility as a burn wound dressing.

Table 2. Strategies for transdermal therapeutic agents delivery enhancement in burn wound healing by using hydrogel systems as the delivery carrier.

Hydrogel composition	Nanoparticles/Nanoparticle-based carriers	Particle Size (nm)	Therapeutic agents	Burn wound model	Findings
	Non-polymeric
Oxidized dextran (ODex), adipic dihydrazide grafted hyaluronic acid (HA-ADH), and quaternized chitosan (HACC)	Silver (Ag) Reducing agent: Chitosan	∼50–190	–	P. aeruginosa infected burn wound in rat model	- Enhanced antibacterial effect against E. coli, S. aureus, and P. aeruginosa compared to the hydrogel only group in both in vitro and in vivo experiments. - Promoted burn wound healing, as evidenced by minimal scar formation, nearly complete re-epithelialization, well-organized collagen deposition, and significant suppression of inflammatory factors compared to other groups, including commercial Ag dressings containing 1.2% ionic silver (Chen et al., 2021).
Carbopol-940	Silver (Ag) Reducing agent: Mimosa tenuifora (plant extract)	∼21	–	Second-degree burn wound in rat model	- Enhanced antibacterial effect against E. coli in vitro, surpassing that of the control gel, gel loaded with Mimosa tenuifora (MtE), and commercially available Ag NPs loaded gel. - Accelerated wound healing in comparison to the control gel, as well as gels loaded with MtE and commercially available Ag NPs (Martínez-Higuera et al., 2021).
Carbomer 934 P	Silver (Ag)	<20	–	Acute burn injury in mouse model	- Enhanced antibacterial activity against MRSA and P. aeruginosa compared to both blank gel and commercially available silver nanoparticles gel. - Prevented bacterial colonization and effectively reduced inflammation, surpassing the effectiveness of both the blank gel and commercially available silver nanoparticle gel. - Accelerated wound healing, characterized by a faster wound closure rate, a higher level of re-epithelialization, increased collagen deposition, and reduced scar formation, in comparison to both the blank gel and a commercially available silver nanoparticles gel (Chen et al., 2020).
Ulvan (green algae Ulva Lactuca Linn extract)	Silver (Ag) Reducing agent: Ulvan	∼13–22	–	Second-degree thermal burn wound in rat model	- Enhanced antibacterial effect against S. epidermidis, E. coli, S. aureus, and P. aeruginosa compared to the hydrogel only group in in vitro experiment. - Accelerated wound closure during the initial 14 days following the burn injury compared to the hydrogel only group and negative control. - Improved re-epithelization compared to the hydrogel only group and negative control (Sulastri et al., 2023).
Sodium alginate and kappa-carrageenan with a concentration ratio of 60:40	Silver (Ag) Reducing agent: Sodium alginate and kappa-carrageenan	∼2–6	–	Second-degree burn wound in mouse model	- Improved antibacterial effect against E. coli and S. aureus compared to the other hydrogels with varying ratios of sodium alginate and kappa-carrageenan concentrations. - Accelerated wound closure during the initial 14 days following the burn injury compared to the other hydrogels with varying ratios of sodium alginate and kappa-carrageenan concentrations. - Improved angiogenesis and collagen deposition at the wound site compared to the other hydrogels with varying ratios of sodium alginate and kappa-carrageenan concentrations (Zia et al., 2020).
Gelatin	Titanium dioxide (TiO2)	15–25	–	Third-degree burn wound in mouse model	- Increased antibacterial activity against S. aureus and P. aeruginosa compared to the gelatin gel only group and SSD 1% ointment in the in vitro experiment. - Promoted wound healing by facilitating wound contraction, stimulating angiogenesis, and promoting fibroblast proliferation and granulation tissue formation compared to only gelatin gel and silver SSD 1% ointment groups (Javanmardi et al., 2018).
Methylcellulose	Silver oxide (AgO)	–	–	Second-degree burn wound in rat model	- Enhanced antibacterial effect against E.coli, S. aureus, and K. pneumoniae compared to the hydrogel only group in in vitro experiment. - Promoted wound healing by suppressing inflammation, enhancing re-epithelialization and collagen deposition compared to control and the hydrogel only groups (Kim et al., 2018).
Carbopol	Nanoemulsion	∼160–180	Curcumin and resveratrol	Second-degree burn wound in rat model	- Improved curcumin and resveratrol skin penetration and retention. - Accelerated wound healing in burnt rats by enhancing antioxidant and anti-inflammatory potential, while also increasing collagen and amino acid levels in the skin compared to the control group, as well as only curcumin-loaded nanoemulgel and resveratrol-loaded nanoemulgel (Alyoussef et al., 2021).
Starch-g-poly (acrylic acid-co-acrylamide) with 0.3 w/v% of starch	Nanoemulsion	175	Myrtus oil	Second-degree burn wound in rat model	- Improved drug sustained release compared to the hydrogel sample containing 1 w/v% of starch. - Enhanced antibacterial effect against E.coli, Candida albican, and MRSA compared to the hydrogel sample with 1 w/v% of starch in in vitro experiment. - Accelerated wound healing compared to the control group, as well as the group treated with myrtus oil nanoemulsion-loaded hydrogel containing 1 w/v% starch and silver sulfadiazine 1% (Moradi et al., 2023).
Poloxamer (P407, P188) and polyvinyl alcohol (PVA)	Plant lipid droplets(CLD)	∼133.5	hFGF2	Deep second-degree burn wound in mouse model	- Achieved controlled and sustained release of CLD-hFGF2 from hydrogel to promote cell proliferation and migration. - Accelerated wound healing rate compared to the control group, CLD-containing hydrogel group, and CLD-hFGF2 group. - Accelerated the re-epithelialization, promoted collagen deposition and angiogenesis compared to other treatment groups (Zhang et al., 2022).
	Polymeric
Poloxamer (P407) and polyvinyl alcohol (PVA)	Gelatin	∼11	Mupirocin	Third-degree burn wound in rat model	- Promoted antibacterial activity against S. epidermis, S.aureus, and P. aeruginosa compared to mupirocin ointment (Kamlungmak et al., 2020). - Enhanced wound healing by lowering inflammation as well as improving wound contraction, angiogenesis, and granulation tissue formation compared to the hydrogel only group and mupirocin ointment (Kamlungmak et al., 2021).
Poly(N-isopropylacrylamide) (PNIPAM)	Silk fibroin-sodium alginate	∼200	Vancomycin	MRSA-infected third-degree burn wound in rat model	- Showed good antibacterial activity against MRSA. - Promoted wound healing by lowering wound inflammation, accelerating angiogenesis, re-epithelialization, and collagen deposition with the synergistic effect of EGF loaded directly into the hydrogel (Rezaei et al., 2020).
Carbopol®934	Polycaprolactone (PCL)	∼225	Fusidic acid (FA)	MRSA-infected burn wound in rat model	- Enhanced antibacterial activity against S.aureus, and MRSA compared to that of FA solution and commercially available FA cream. - Enhanced FA retention on skin surface compared to both FA-based hydrogel and the commercially available FA cream. - Accelerated wound contraction and re-epithelization, decreased the bacterial colonization in wounds compared to other treatment groups (Ullah et al., 2023).
Carboxymethyl chitosan (CMCS) and sodium alginate (SA)	Poly(lactic-co-glycolic acid) (PLGA)	∼420	bFGF	MRSA-infected burn wound in mouse model	- Promoted wound healing by accelerating wound closure, enhancing collagen deposition and re-epithelialization - Inhibited bacterial growth and controlled inflammation in both in vitro and in vivo experiments with the synergistic effect of porphyrin photosensitizer sinoporphyrin sodium loaded directly into the hydrogel (Mai et al., 2020).
	Combination of non-polymeric and polymeric
Recombinant methacrylated collagen and glycidyl methacrylated quaternary ammonium chitosan	Liposome and cyclodextrin (CD) metal organic skeleton loaded with ultrafine silver nanoparticles	∼122 and ∼93	Asiaticoside (AS)	E. coli and S. aureu-infected burn wound in rat model	- Enhanced antibacterial activity against E. coli and S. aureu in the presence of ultrafine silver nanoparticles within the hydrogel. - Promoted the in vitro cell migration and tube formation in the presence of AS-loaded liposomes within the hydrogel. - Accelerated the wound healing rate and lowered the bacteria remaining in the wound area compared to the control group, hydrogel only group, ultrafine silver nanapoarticles-loaded hydrogel group and commercially available Aquacel Ag group. - Enhanced wound healing by lowering inflammation, improving cell proliferation, collagen deposition and angiogenesis compared to the control group, hydrogel only group, ultrafine silver nanapoarticles-loaded hydrogel group and commercially available Aquacel Ag group (Feng et al., 2023).

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