Human Epidermal Membrane Research Articles

Mechanistic Evaluation of Hydration Effects on the Human Epidermal Permeation of Salicylate Esters.

We sought to understand when and how hydration enhances the percutaneous absorption of salicylate esters. Human epidermal membrane fluxes and stratum corneum solubilities of neat and diluted solutions of three esters were determined under hydrated and dehydrated conditions. Hydration doubled the human epidermal flux seen for methyl and ethyl salicylate under dehydrated conditions and increased the flux of neat glycol salicylate 10-fold. Mechanistic analyses showed that this hydration-induced enhancement arises mainly from an increase in the stratum corneum diffusivity of the three esters. Further, we showed that unlike methyl and ethyl salicylate, glycol salicylate is hygroscopic and the ∼10-fold hydration-induced flux enhancement seen with neat glycol salicylate may be due to its ability to hydrate the stratum corneum to a greater extent. The hydration-induced enhancements in in vitro epidermal flux seen here for glycol and ethyl salicylate were similar to those reported for their percutaneous absorption rates in a comparable in vivo study, whilst somewhat higher enhancement was seen for methyl salicylate in vivo. This may be explained by a physiologically induced self enhancement of neat methyl salicylate absorption in vivo which is not applicable in vitro.

Estimating Maximal In Vitro Skin Permeation Flux from Studies Using Non-sink Receptor Phase Conditions.

This study explored the impact of non-sink receptor conditions on the in vitro skin permeation test (IVPT) and sought to estimate equivalent sink condition IVPT data. Simulated diffusion model and experimental IVPT data were generated for ethyl salicylate across human epidermal membranes in Franz diffusion cells using six different receptor phases, with a 10 fold variation in ethyl salicylate solubility. Both simulated and experimental IVPT - time profiles were markedly affected by receptor phase solubility and receptor sampling rates. Similar sink condition equivalent estimated maximum fluxes were obtained by nonlinear regression and adjustment of linear regression estimates of steady state flux for relative saturation of the receptor phase over time for the four receptor phases in which the ethyl salicylate was relatively soluble. The markedly lower steady - state fluxes found for the other two phases in which ethyl salicylate was less soluble was attributed to an aqueous solution boundary layer effect. Non-sink receptor phase IVPT data can be used to derive equivalent sink receptor phase IVPT data provided the receptor phase solubility and hydrodynamics are sufficient to minimise the impact of aqueous diffusion layers on IVPT data.

Synergistic Skin Penetration Enhancer and Nanoemulsion Formulations Promote the Human Epidermal Permeation of Caffeine and Naproxen

We examined the extent of skin permeation enhancement of the hydrophilic drug caffeine and lipophilic drug naproxen applied in nanoemulsions incorporating skin penetration enhancers. Infinite doses of fully characterized oil-in-water nanoemulsions containing the skin penetration enhancers oleic acid or eucalyptol as oil phases and caffeine (3%) or naproxen (2%) were applied to human epidermal membranes in Franz diffusion cells, along with aqueous control solutions. Caffeine and naproxen fluxes were determined over 8 h. Solute solubility in the formulations and in the stratum corneum (SC), as well as the uptake of product components into the SC were measured. The nanoemulsions significantly enhanced the skin penetration of caffeine and naproxen, compared to aqueous control solutions. Caffeine maximum flux enhancement was associated with a synergistic increase in both caffeine SC solubility and skin diffusivity, whereas a formulation-increased solubility in the SC was the dominant determinant for increased naproxen fluxes. Enhancements in SC solubility were related to the uptake of the formulation excipients containing the active compounds into the SC. Enhanced skin penetration in these systems is largely driven by uptake of formulation excipients containing the active compounds into the SC with impacts on SC solubility and diffusivity.

Iontophoretic delivery of lipophilic and hydrophilic drugs from lipid nanoparticles across human skin

The combined effects of iontophoresis and lipid nanoparticles on drug delivery across human epidermal membrane (HEM) were investigated. The delivery of lipophilic and hydrophilic drugs, all trans-retinoic acid (ATRA), salicylate (SA), and acyclovir (ACV), across HEM from lipid nanoparticles, solid lipid nanoparticles (SLN) and nanostructured lipid carriers (NLC), was compared in passive and iontophoresis experiments in vitro. Iontophoresis experiments were also performed with synthetic Nuclepore membrane for comparison. Drug distribution in the skin after iontophoretic delivery with the lipid nanoparticles was examined using a model probe rhodamine B base (RhoB). The drug-loaded lipid nanoparticles had average sizes of ∼118–169nm and a negative zeta potential. Iontophoresis did not enhance the delivery of ATRA across HEM from SLN and NLC. However, HEM distribution study of RhoB suggested that lipophilic drugs could be delivered into the deeper layer of the skin following iontophoretic delivery of the drugs from the lipid nanoparticles. Iontophoresis enhanced the delivery of hydrophilic drug SA with the lipid nanoparticles. Similarly, iontophoresis enhanced the delivery of ACV when it was loaded in SLN. These results suggest that lipid nanoparticles are a promising drug delivery method that can be combined with iontophoresis to improve skin delivery of hydrophilic drugs.

Evaluation of β-blocker Gel and Effect of Dosing Volume for Topical Delivery

Although topical administration of β-blockers is desired because of the improved therapeutic efficacy and reduced systemic adverse effects compared with systemic administration in the treatment of infantile hemangioma, the permeation of β-blockers across skin under finite dose conditions has not been systematically studied and an effective topical β-blocker formulation for skin application is not available. The present study evaluated the permeation of β-blockers propranolol, betaxolol, and timolol across human epidermal membrane (HEM) from a topical gel in Franz diffusion cells in vitro under various dosing conditions. The effects of occlusion and dosing volume on percutaneous absorption of β-blockers from the gel were studied. The permeation data were compared with those of finite dose diffusion theory. The results showed that skin permeation of β-blockers generally could be enhanced two to three times by skin occlusion. The cumulative amounts of β-blockers permeated across HEM increased with increasing dosing volume. An adequate fit was obtained between the theoretical curve and experimental permeation data, indicating that the experimental results of the gel are consistent with finite dose diffusion theory. In conclusion, the findings suggest the feasibility of using topical gels of β-blockers for infantile hemangioma treatment and topical application with skin occlusion is preferred.

Effects of solvent on percutaneous absorption of nonvolatile lipophilic solute

Understanding the effects of solvents upon percutaneous absorption can improve drug delivery across skin and allow better risk assessment of toxic compound exposure. The objective of the present study was to examine the effects of solvents upon the deposition of a moderately lipophilic solute at a low dose in the stratum corneum (SC) that could influence skin absorption of the solute after topical application. Skin permeation experiments were performed using Franz diffusion cells and human epidermal membrane (HEM). Radiolabeled corticosterone (3H-CS) was the model permeant. The solvents used had different evaporation and skin penetration properties that were expected to impact skin deposition of CS and its absorption across skin. The results show no correlation between the rate of absorption of the permeant and the rate of solvent evaporation/penetration with ethanol, hexane, isopropanol, and butanol as the solvent; all of these solvents have fast evaporation rates (complete evaporation in <30min after application). This suggests no differences in solvent-induced deposition of CS in the SC for the fast-evaporating solvents. The results of these fast-evaporating solvents were different from those of water, propylene glycol, and polyethylene glycol 400, that a relationship between permeant absorption and the rate of solvent evaporation was observed.

Bacterial cellulose membranes as transdermal delivery systems for diclofenac: In vitro dissolution and permeation studies

Bacterial cellulose (BC) membranes were explored as novel nanostructured transdermal delivery systems for diclofenac sodium salt (a typical non-steroidal anti-inflammatory drug). Diclofenac sodium salt loaded BC membranes were prepared through a simple methodology, using glycerol as plasticizer, and characterized in terms of structure, morphology and swelling behavior. The membranes were very homogeneous, quite flexible and presented a considerably higher swelling behavior when compared with pure BC. In vitro diffusion studies with Franz cells, were conducted using human epidermal membranes, and showed that the incorporation of diclofenac in BC membranes provided similar permeation rates to those obtained with commercial patches and substantially lower than those observed with a commercial gel. This release profile together with the ease of application and the simple preparation and assembly of the drug-loaded membranes clearly indicates the enormous potentialities of using BC membranes for transdermal administration of diclofenac.

Evaluation of diclofenac prodrugs for enhancing transdermal delivery

Objective: The purpose of this study was to evaluate the approach of using diclofenac acid (DA) prodrugs for enhancing transdermal delivery.Methods: Methanol diclofenac ester (MD), ethylene glycol diclofenac ester (ED), glycerol diclofenac ester (GD) and 1,3-propylene glycol diclofenac ester (PD) were synthesized and evaluated for their physicochemical properties such as solubilities, octanol/water partition coefficients, stratum corneum/water partition coefficients, hydrolysis rates and bioconversion rates. In vitro fluxes across human epidermal membrane (HEM) in the Franz diffusion cell were determined on DA-, MD-, ED-, GD- and PD-saturated aqueous solutions.Results: The formation of GD and ED led to the prodrugs with higher aqueous solubilities and lower partition coefficients than those of the parent drug. Prodrugs with improved aqueous solubility showed better fluxes across HEM in aqueous solution than that of the parent drug, with GD showing the highest aqueous solubility and also the highest flux. There is a linear relationship between the aqueous solubility and flux for DA, ED and PD, but GD and MD deviated from the linear line.Conclusion: Diclofenac prodrugs with improved hydrophilicity than the parent drug could be utilized for enhancing transdermal diclofenac delivery.

Evaluation of Skin Permeation of β-Blockers for Topical Drug Delivery

β-Blockers have recently become the main form of treatment of infantile hemangiomas. Due to the potential systemic adverse effects of β-blockers, topical skin treatment of the drugs is preferred. However, the effect and mechanism of dosage form pH upon skin permeation of these weak bases is not well understood. To develop an effective topical skin delivery system for the β-blockers, the present study evaluated skin permeation of β-blockers propranolol, betaxolol, timolol, and atenolol. Experiments were performed in side-by-side diffusion cells with human epidermal membrane (HEM) in vitro to determine the effect of donor solution pH upon the permeation of the β-blockers across HEM. The apparent permeability coefficients of HEM for the β-blockers increased with their lipophilicity, suggesting the HEM lipoidal pathway as the main permeation mechanism of the β-blockers. The pH in the donor solution was a major factor influencing HEM permeation for the β-blockers with a 2- to 4-fold increase in the permeability coefficient per pH unit increase. This permeability versus pH relationship was found to deviate from theoretical predictions, possibly due to the effective stratum corneum pH being different from the pH in the donor solution. The present results suggest the possibility of topical treatment of hemangioma using β-blockers.

Predicting skin penetration of actives from complex cosmetic formulations: an evaluation of inter formulation and inter active effects during formulation optimization for transdermal delivery

Twenty products, containing a radiolabelled form of each active in typical cosmetic formulations, were made and applied to female human epidermal membranes mounted in Franz diffusion cells for 48h under 'in use' conditions. The products consisted of combinations of five formulations (a hydro-alcoholic gel, an oil in water emulsion, a water in oil emulsion, a microemulsion and an oil) with four model drug actives (testosterone, hydrocortisone, 5-fluorouracil and ketoconazole). Steady-state flux appeared to be reached by 8h and maintained for all products, other than for the microemulsions, consistent with the actives being present in the residual formulation on the skin at saturation. The recovery for each active at the end of the 48-h study (from a series of stratum corneum tape strips, the remaining skin, cumulative amount penetrating into the receptor solution, product washed from the skin and on the donor chamber cap) ranged from 86.5% to 100.6%. The rank order of the fluxes for the actives from the hydro-alcoholic gel is consistent with the known active molecular size and polarity determinants for maximum epidermal flux. Actives with similar steady-state (maximum) fluxes from a range of formulations had retention in the stratum corneum and similar transport rate constants through the stratum corneum. The microemulsion formulation significantly enhanced both the stratum corneum steady-state flux and transport rate constant for 5-fluorouracil, hydrocortisone and testosterone. The penetration flux of each active could be related to its size and polarity and appeared maximal when the actives in the different cosmetic formulations applied to the skin under 'in use' conditions were likely to remain in the residual product on the skin as a saturated solution after solvent evaporation. Enhanced penetration fluxes can be achieved by formulation selection and an appropriate choice/mix of emollients/adjuvants. The principles described here provide a framework for understanding the delivery of cosmetic ingredients from various formulations.

In vitro and in vivo assessment of the effect of Laurus novocanariensis oil and essential oil in human skin

Laurus novocanariensis is an endemic plant from the Madeira Island forest that derives a fatty oil, with a strong spicy odour, from its berries that has been used for centuries in traditional medicine to treat skin ailments. This work aimed to investigate the effect of the application of both the oil and its essential oil on normal skin, to assess their safety and potential benefits. Diffusion studies with Franz cells using human epidermal membranes were conducted. The steady-state fluxes of two model molecules through untreated skin were compared with those obtained after a 2-h pre-treatment with either the oil or the essential oil. Additionally, eleven volunteers participated in the in vivo study that was conducted on the forearm and involved daily application of the oil for 5 days. Measurements were performed every day in the treated site with bioengineering methods that measure erythema, irritation and loss of barrier function. Slightly higher steady-state fluxes were observed for both the lipophilic and the hydrophilic molecule when the epidermal membranes were pre-treated. Nevertheless, such differences had no statistical significance, which seems to confirm that neither the oil nor the essential oil impaired the epidermal barrier. Results collected with the Chromameter, the Laser Doppler Flowmeter and the visual scoring are in agreement with those established in the in vitro study. They indicate that the repeated application of the oil did not cause erythema, because the results observed in the first day of the study were maintained throughout the week. Application of the oil did not affect the skin barrier function, because the transepidermal water loss remained constant throughout the study. The stratum corneum hydration was slightly reduced on days 4 and 5. This work shows that both the oil and the essential oil were well tolerated by the skin and did not cause significant barrier impairment or irritation.

Biocellulose Membranes as Supports for Dermal Release of Lidocaine

Biocellulose (BC) is a highly pure form of cellulose, produced in the form of a swollen membrane, with several applications in the biomedical area. In this study, the behavior of BC membranes as systems for topical delivery of lidocaine was evaluated. The BC-lidocaine membranes were prepared and characterized in terms of structural and morphological properties. A uniform distribution of the drug inside the BC membranes was observed. In vitro diffusion studies with Franz cells were conducted using human epidermal membranes and showed that the permeation rate of the drug in BC membranes was slightly slower than that obtained with the conventional systems, which was attributed to the establishment of interactions between the lidocaine molecules and the BC membrane, as evidenced by FTIR and NMR analysis. These results indicate that this methodology can be successfully applied for the dermal administration of lidocaine regarding the release profile and ease of application.

In vitro Human Epidermal Penetration of 1-Bromopropane

1-Bromopropane (1-BP; CAS number 106-94-5), also known as n-propyl bromide, is a halogenated short-chain alkane used as an organic solvent with numerous commercial and industrial applications, including garment dry cleaning and vapor degreasing of metals. The purpose of this study was to determine the dermal absorption characteristics and corrosivity of 1-BP. Heat-separated human epidermal membranes were mounted on static diffusion cells. Different exposure scenarios were studied (infinite dose, finite dose, and transient exposure) using neat 1-BP and saturated aqueous solution as donor. Steady-state fluxes for infinite-dose neat 1-BP exposure averaged 625 to 960 μg cm−2 h−1. The finite-dose (10 μl/cm2 = 13.5 mg/cm2) unoccluded donor resulted in penetration of <0.2% of the applied dose (22 μg/cm2). A 10-min transient exposure to infinite dose resulted in total penetration of 179 μg/cm2. Steady-state 1-BP fluxes from neat application of a commercial dry cleaning solvent were similar (441 to 722 μg cm−2 h−1). The permeability coefficient of 1-BP in water vehicle was 0.257 ± 0.141 cm/h. The absorption potential of 1-BP following dermal exposure is dependent upon the type and duration of exposure. Donor losses due to evaporation were approximately 500-fold greater than dermal absorption flux; evaporation flux was 420 mg cm−2 h−1. 1-BP is cytotoxic but not corrosive, based on results from a cultured reconstructed human epidermal model (EpiDerm Skin Corrosivity Test).

Cryopreservation of tissue-engineered epithelial sheets in trehalose

Tissue-engineered epidermal membranes are useful for clinical wound healing. To facilitate these products in the clinic, optimized storage methods need to be developed. We studied the efficiency of extracellular trehalose at various concentrations for cryopreserving human tissue-engineered epidermal membranes compared with that of dimethyl-sulfoxide (DMSO) used by most organ banks for cryopreserving skin grafts and artificial skin substitutes. Keratinocyte (KC) viability, proliferation and marker expression following cryopreservation in trehalose were examined with similar results to those using DMSO. Trehalose concentration (0.4 m) was optimized according to the described cellular activities following cryopreservation. Artificial epidermal substitutes were then cryopreserved in trehalose at the optimized concentration. Cell viability, growth factor secretion and wound healing properties of cryopreserved artificial epidermal substitutes using nude mice were examined and compared with those of DMSO cryopreservation. Cryopreservation with trehalose enhanced human KC viability in suspension and artificial skin substitutes. In addition, trehalose cryopreservation provided fast recovery of EGF and TGF-β1 secretion by KCs after thawing. When transplanted into nude mice, trehalose-cryopreserved artificial skin repaired skin defects in a similar manner to that of a non-cryopreserved control. Moreover, trehalose-cryopreserved artificial skin resulted in engraftment and wound closure that was significantly enhanced compared with that of DMSO-cryopreserved epidermal membranes. The results indicate that the use of trehalose improves cryopreservation of tissue-engineered epithelial sheets.

Negligible penetration of incidental amounts of alpha-hydroxy acid from rinse-off personal care products in human skin using an in vitro static diffusion cell model

Alpha-hydroxy acids (AHAs), primarily glycolic and lactic acids, are widely used in cosmetics to alleviate dyspigmentation, photodamage, and other aging skin conditions and as pH adjusters. Glycolic acid reportedly enhances skin damage after repeated ultraviolet light exposure, e.g., increased sunburn cell formation. This study assessed potential in vitro skin penetration of lactic acid and malic acid incorporated into rinse-off personal care products, compared with rinse-off and leave-on exposures to glycolic acid (10%, pH3.5) in a reference lotion. Radiolabeled AHA-fortified shampoo, conditioner, and lotion were evenly applied as single doses to human epidermal membranes mounted in static diffusion cells (not occluded). Exposures were 1–3min (rinse-off) or 24h (leave-on). Epidermal penetration of malic acid and lactic acid from the rinse-off shampoo and conditioner, respectively, was negligible, with >99% removed by rinsing, a negligible portion remaining in the stratum corneum (⩽0.15%), and even less penetrating into the viable epidermis (⩽0.04%). Glycolic acid penetration from the leave-on reference lotion was 1.42μgequiv./cm2/h, with total absorbable dose recovery (receptor fluid plus epidermis) of 2.51%, compared to 0.009%, 0.003%, and 0.04% for the rinse-off reference lotion, shampoo (malic acid), and conditioner (lactic acid) exposures, respectively. Dermal penetration of AHAs into human skin is pH-, concentration-, and time-dependent. Alpha-hydroxy acids in rinse-off shampoos and conditioners are almost entirely removed from the skin within minutes by rinsing (resulting in negligible epidermal penetration). This suggests that ultraviolet radiation-induced skin effects of AHA-containing rinse-off products are negligible.

Transport Behavior of Hairless Mouse Skin During Constant Current DC Iontophoresis I: Baseline Studies

The fluxes of charged and nonionic molecules across hairless mouse skin (HMS) were induced by direct current iontophoresis and used to characterize the transport pathways of the epidermal membrane. Experimental data were used to determine permeability coefficients from which the effective pore radii (Rp) of the transport pathways were calculated. Permeants used in these experiments were nonionic permeants (urea, mannitol, and raffinose), monovalent cationic permeants (sodium, tetraethylammonium, and tetraphenylphosphonium ions), and monovalent anionic permeants (chloride, salicylate, and taurocholate ions). The Rp estimates obtained by the anionic permeant pairs were 49, 22, and 20 Å for the chloride/salicylate (Cl:SA), chloride/taurocholate (Cl:TC), and salicylate/taurocholate (SA:TC) pairs, respectively; with the cationic permeant pairs, the Rp values obtained were 19, 30, and 24 Å for the sodium/tetraethylammonium (Na:TEA), sodium/tetraphenylphosphonium (Na:TPP), and the tetraethylammonium/tetraphenylphosphonium (TEA:TPP) pairs, respectively. Rp estimates for HMS obtained from nonionic permeant experiments ranged from 6.7 to 13.4 Å. When plotted versus their respective diffusion coefficients, all of the permeability coefficients for the cationic permeants were greater than those of the anionic permeants. Additionally, the magnitudes of permeability coefficients determined in the current study with HMS were of the same order of magnitude as those previously determined in our laboratory using human epidermal membrane under similar iontophoresis conditions.

Flexible Nanosomes (SECosomes) Enable Efficient siRNA Delivery in Cultured Primary Skin Cells and in the Viable Epidermis of Ex Vivo Human Skin

AbstractThe extent to which nanoscale‐engineered systems cross intact human skin and can exert pharmacological effects in viable epidermis is controversial. This research seeks to develop a new lipid‐based nanosome that enables the effective delivery of siRNA into human skin. The major finding is that an ultraflexible siRNA‐containing nanosome—prepared using DOTAP, cholesterol, sodium cholate, and 30% ethanol—penetrates into the epidermis of freshly excised intact human skin and is able to enter into the keratinocytes. The nanosomes, called surfactant‐ethanol‐cholesterol‐osomes (SECosomes), show excellent size, surface charge, morphology, deformability, transfection efficiency, stability, and skin penetration capacity after complexation with siRNA. Importantly, these nanosomes have ideal characteristics for siRNA encapsulation, in that the siRNA is stable for at least 4 weeks, they enable highly efficient transfection of in vitro cultured cells, and are shown to transport siRNA delivery through intact human skin where changes in the keratinocyte cell state are demonstrated. It is concluded that increasing flexibility in nanosomes greatly enhances their ability to cross the intact human epidermal membrane and to unload their payload into targeted epidermal cells.

Relationship Between the Enhancement Effects of Chemical Permeation Enhancers on the Lipoidal Transport Pathway Across Human Skin Under the Symmetric and Asymmetric Conditions In Vitro

Previously, the mechanisms of action of chemical permeation enhancers (CPEs) were studied, and a quantitative structure-enhancement relationship for the lipoidal transport pathway of the stratum corneum was established under symmetric and equilibrium conditions. The present study examined whether the effects of CPEs under the asymmetric conditions could be predicted by those determined using the symmetric transport experimental approach. Both symmetric (same CPE concentration in both donor and receiver chambers) and asymmetric (CPE in the donor chamber only and phosphate-buffered saline solution in the receiver) transport experiments were carried out in a two-chamber side-by-side diffusion cell with human epidermal membrane (HEM). Corticosterone was the model permeant to probe the effects of CPEs upon the HEM lipoidal pathway under these conditions. A correlation between the experimental enhancement factors under the asymmetric conditions (E (Asym)) and those under the symmetric conditions (E (Sym)) was observed. The potencies of CPEs based on their donor concentrations are related to their lipophilicities. The results suggest that the symmetric configuration findings in the previous studies can be used to explain the effects of CPEs under the asymmetric condition likely encountered in practice and to understand drug delivery enhancement in transdermal enhancer formulation development.

Construction and Clinical Application of a Human Tissue-Engineered Epidermal Membrane

Prolonged healing times and hypertrophic scarring of the donor site for split-thickness-skin grafts thicker than 0.3 mm are common problems that continue to challenge plastic surgeons in the clinic. As such, a human tissue-engineered epidermal membrane was constructed to promote wound healing and reduce scar hypertrophy. An artificial allogenic epidermis was created in vitro using human keratinocytes and chitosan-gelatin membrane. Split-thickness skin graft donor sites were divided into three treatment groups: those covered with the combined keratinocyte/chitosan-gelatin membrane, those covered with chitosan-gelatin membrane only (control group), and those covered with traditional petroleum jelly gauze (blank group). The degree of wound healing was assessed at various time points after the operation by gross observation, hematoxylin and eosin staining, immunohistochemistry, and an assay of type I collagen using the picrosirius polarization method. Reverse-transcriptase polymerase chain reaction detection of the Y chromosome was also performed to distinguish between sexes. Over a 6-month observation period, treatment with the human tissue-engineered epidermal membrane (keratinocyte/chitosan-gelatin) appeared to decrease donor-site healing time (48 wounds in 24 cases). Average healing time was 8.1 +/- 1.3 days for the keratinocyte/chitosan-gelatin group, 16.4 +/- 1.7 days for the chitosan-gelatin group, and 22.9 +/- 4.2 days for the blank group. The artificial epidermis survived well and maintained a normal structure. Furthermore, hypertrophic scar formation was less severe for these wounds. Keratinocyte/chitosan-gelatin membranes can be constructed in vitro and survive temporarily in vivo. They can be used to promote wound healing and reduce the severity of hypertrophic scarring of skin graft donor sites.

Discussion: Construction and Clinical Application of a Human Tissue-Engineered Epidermal Membrane

Discussion: Construction and Clinical Application of a Human Tissue-Engineered Epidermal Membrane