Hydrogel dressing

Hydrogel dressings exhibit chemical or physical cross-linking. Chemical cross-linking involved formation of covalent bonds between polymer chains. Chemically cross-linked hydrogel dressings are synthesized by chain-growth polymerization, step-growth polymerization, enzymes, or irradiation polymerization. Synthetic dressings incorporating nanoparticles such as PVA and polyethylene glycol (PEG) are assembled using chemical cross-linking mechanisms.[9][10] Physically cross-linked hydrogel dressings are assembled via ionic interaction, hydrogen bonding, hydrophobic interactions, or crystallization. Physically cross-linked hydrogels disintegrate due to local changes in pH, ionic strength, and temperature.[3] Natural dressings incorporating polysaccharides and proteoglycans/proteins form a 3D network using physical cross-linking.[11] Hydrogel dressings mimic the cross-linked 3D network of extracellular matrix fibers in human skin.[1]

Hydrogels can be formed through a self-assembly process in which monomers diffuse in solution then form non covalent interactions. Hydrogels used in wound dressings can be self-assembled upon addition of divalent metal cations or electrically charged polysaccharides due to electrostatic interactions.[12][13] Self-assembly via hydrophobic interactions can be induced in amphiphilic polysaccharides-based gels by addition of water; it can also be induced in non amphiphilic polysaccharide-based hydrogels by addition of hydrophobic grafts.[8][12]

Cross-linking of soluble hydrophilic monomers forms a 3D insoluble netted structure which can incorporate a large amount of water.[14] The 3D polymeric network of hydrogels is highly hydrated with 90-99% water w/w; it is capable of binding many times more water molecules when assembled than in the uncross-linked state.[2][3] Hydrogel dressings can absorb up to 600 times their initial amount of water, including fluid-based wound exudates.[2][14] Hydrogels are effective biomaterials for wound dressings and tissue engineering because they exchange fluid, hydrating necrotic tissues.[2][6] The absorption of secretions causes the hydrogel dressing to swell, expanding the cross links in the polymer chains.[6] The expanded 3D cross-linked network can irreversibly incorporate pathogens and detritus, thereby removing them from the wound.[6]

Some hydrogel dressings have intrinsic antimicrobial properties. Hydrogel dressings formed from antimicrobial peptides (AMPs) and chitosan have inherent antimicrobial activity.[15][16][17] The antimicrobial properties of hydrogel dressings can be enhanced by addition of metal nanoparticles, antibiotics, or other antimicrobial agents.[15][18][19][20] Silver and gold nanoparticles can also be incorporated into hydrogel dressings to enhance antimicrobial activity.[15] Some hydrogel dressings have antibiotics such as ciprofloxacin and amoxicillin incorporated into their structure which are unloaded into the wound as fluid is exchanged.[15][19] Some hydrogel dressings have incorporated stimuli-responsive nitric oxide-releasing agents and other antimicrobial agents.[15][20]

Hydrogel dressings can adhere directly to the wound bed under normal physiological conditions via oxidation-reduction reactions of quinones.[2][21] The adhesive properties of hydrogels have been shown to be enhanced by addition of positively charged microgels (MR) into the 3D matrix to increase electrostatic and hydrophobic interactions.[22]

Wound dressings should be stretchable to prevent tearing. Hai Lei et al. demonstrated that poor elasticity and hysteresis in naturally-derived protein-based hydrogels can be remedied by the addition of polyprotein cross-linkers.[23] The flexibility of hydrogels can also be enhanced by incorporating microgels into the matrix.[22][24] Hydrogel dressings mimic the fibrous nature of native ECM to maintain cell-to-cell communication at the wound bed for tissue regeneration.[24]

Self-healing hydrogels automatically and reversibly repair damage done due to mechanical and chemical stress.[25] Self-healing mechanisms can involve "dynamic covalent bonding, non-covalent interactions" and mixed interactions.[25] Covalent interactions involved in self-healing include Schiff base formation and disulfide exchange.[25] Non-covalent interactions are generally less stable and make the hydrogel more sensitive to microenvironmental changes (e.g. pH, temperature).[25] Some hydrogel dressings are self-healing due to mixed mechanisms such as host-guest and protein-ligand interactions.[25]

Hydrogel dressings are available in sheet, amorphous, impregnated, or sprayable forms.[15][26][27][28][29] Sheet-form hydrogel dressings are non-adhesive against the wound and are effective in healing partial-thickness wounds.[26] Amorphous hydrogels are more effective in treatment of full-thickness wounds than sheet-form dressings because they can conform to the shape of the wound bed and they facilitate autolytic debridement.[27] Impregnated hydrogel dressings are dry dressings (e.g. gauzes) saturated with an amorphous hydrogel.[28] Sprayable hydrogel dressings are composed of amorphous hydrogels which rapidly increase in viscosity after application.[29] Sprayable hydrogels have also been shown to increase the penetration and efficacy of therapeutic agents.[2]

"Smart" hydrogels which are stimuli-responsive (i.e. thermoresponsive, bioresponsive, pH-responsive, photoresponsive, and redox-responsive) are also being produced.[3] pH-responsive hydrogel dressings which release growth factors and antibiotic agents as the pH of the wound increases from normal skin levels (pH 4–6) to internal levels (pH ~7.4).[30] Redox-responsive hydrogel dressings can be disintegrated on-demand by addition of a reducing agent.[31] Assembly of the 3D network of photoresponsive hydrogel dressings is initiated by UV radiation.[32] Thermoresponsive hydrogel dressings which exhibit temperature-dependent sol-gel transition and/or temperature-dependent drug release.[33][34]

Polysaccharide-based hydrogel dressings have been synthesized from polymers such as hyaluronic acid, chitin, chitosan, alginate, and agarose.[1][40][47][48][49] Naturally-derived protein/proteoglycan hydrogel dressings have been synthesized from polymers such as collagen, gelatin, kappa-carrageenan, and fibrin.[1][49][50][51]  

Synthetic hydrogel dressings may be derived from synthetic polymers such as polyvinyl alcohol (PVA), poly(ethylene glycol) (PEG), polyurethane (PU), and poly(lactide-co-glycolide) (PLGA).[1][52][53] Synthetic hydrogel dressings may also be formed from designer peptides.[8][54] Researchers are applying 3D printing to the synthesis of hydrogel dressings.[55][56]

Hydrogels may be modified to incorporate metal cations (e.g. copper (II)), degradable linkers (e.g. dextran), and adhesive functional groups (e.g. RGD).[1] Integrating biological derivatives into synthetic hydrogels allows producers to tailor binding affinities and specificity, mechanical properties, and stimuli-responsive properties.[1]