Release Of Epidermal Growth Factor Research Articles

Oral Soft Tissue Regeneration Using Nano Controlled System Inducing Sequential Release of Trichloroacetic Acid and Epidermal Growth Factor.

The effect of nano controlled sequential release of trichloroacetic acid (TCA) and epidermal growth factor (EGF) on the oral soft tissue regeneration was determined. Hydrophobically modified glycol chitosan (HGC) nano controlled system was developed for the sequential release of TCA and EGF, and the release pattern was identified. The HGC-based nano controlled release system was injected into the critical-sized defects created in beagles' palatal soft tissues. The palatal impression and its scanned body was obtained on various time points post-injection, and the volumetric amount of soft tissue regeneration was compared among the three groups: CON (natural regeneration control group), EXP1 (TCA-loaded nano controlled release system group), EXP2 (TCA and EGF individually loaded nano controlled release system). DNA microarray analysis was performed and various soft tissue regeneration parameters in histopathological specimens were measured. TCA release was highest at Day 1 whereas EGF release was highest at Day 2 and remained high until Day 3. In the volumetric measurements of impression body scans, no significant difference in soft tissue regeneration between the three groups was shown in two-way ANOVA. However, in the one-way ANOVA at Day 14, EXP2 showed a significant increase in soft tissue regeneration compared to CON. High correlation was determined between the histopathological results of each group. DNA microarray showed up-regulation of various genes and related cell signaling pathways in EXP2 compared to CON. HGC-based nano controlled release system for sequential release of TCA and EGF can promote regeneration of oral soft tissue defects.

Analysis of the effect of trichloroacetic acid and epidermal growth factor release on cytoskeleton gene expression using the nano-controlled releasing system

Analysis of the effect of trichloroacetic acid and epidermal growth factor release on cytoskeleton gene expression using the nano-controlled releasing system

Hypoxic Pulmonary Endothelial Cells Release Epidermal Growth Factor which Results in Vascular Smooth Muscle Cell Arginase 2 Expression and Proliferation

The hallmark of pulmonary hypertension (PH) is vascular remodeling leading to alterations in hemodynamics and vasoreactivity. Endothelial cells (EC) are central in the response of a vessel to stimuli associated with PH. EC can proliferate contributing to vascular remodeling, but likely a more important role of EC is the release of factors that induce proliferation in the underlying smooth muscle cells (SMC) leading to intimal thickening. Hypoxia is associated with the development of PH in certain human diseases. We have previously shown that human pulmonary microvascular EC (hPMVEC) respond to hypoxia with proliferation that is dependent on arginase 2 up‐regulation. This arginase 2 up‐regulation is mediated by the release of epidermal growth factor (EGF) and resultant activation of EGF receptors (EGFR) on hPMVEC. We hypothesized that the release of EGF by hPMVEC would also result in proliferation of human pulmonary arterial SMC (hPASMC) via EGFR‐mediated arginase 2 up‐regulation. To test this hypothesis, we used conditioned media (CM) from hPMVEC grown either in normoxia or hypoxia to study the role of EGF released by hPMVEC on the regulation of arginase 2 and proliferation in hPASMC. When hPASMC were grown with CM from hypoxic hPMVEC there was a 9‐fold induction of arginase 2 protein levels and more than a doubling of viable hPASMC numbers compared to hPASMC grown with CM from normoxic hPMVEC. In another experiment, hPVMEC were transfected with a scramble siRNA (scramble) or an siRNA against EGF (siEGF) and then the hPMVEC placed in hypoxia to generate conditioned media. In the hPASMC treated with the CM from siEGF‐treated hypoxic hPMVEC there were lower levels of arginase 2 protein than in the hPASMC grown in CM from hPMVEC grown in normoxia; and substantially less arginase 2 than in hPASMC treated with CM from hypoxic hPMVEC treated with scramble. Furthermore, hPASMC treated with hypoxic CM from siEGF‐treated hPMVEC had substantially lower viable cell numbers than in hPASMC treated with hypoxic CM from scramble‐treated hPMVEC. When hPASMC were treated with hypoxic CM from hPMVEC the addition of an EGF neutralizing antibody to the CM prevented the increase in viable cell numbers seen with hypoxic CM. When hPASMC were transfected with siRNA against EGFR and then treated with hypoxic CM from hPMVEC the hypoxia‐induced increase in arginase 2 protein levels and viable cell numbers were prevented. These data demonstrate that hPMVEC release EGF, which can activate EGFR on hPASMC to induce arginase 2 protein expression and increase viable cell numbers. We speculate that EGF neutralizing antibodies or EGFR blocking antibodies are potential therapeutics to prevent and/or attenuate the vascular remodeling seen in PH associated with hypoxia.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Characterization of titanium surface coated with epidermal growth factor and its effect on human gingival fibroblasts

ObjectivesDifferent strategies, such as modifications on the implant abutments surface have been proposed to accelerate and improve the formation of the biological seal (BS). The aim of this study was to characterize a titanium (Ti) surface impregnated with epidermal growth factor (EGF) and to assess its influence on the metabolism and adhesion of oral mucosal cells. DesignTi discs were coated with EGF (100 nM) conjugated with a fluorophore and analyzed by fluorescence microscopy. The surface roughness analysis (Ra) of the EGF-coated Ti was performed by confocal microscopy. The EGF released in the wet environment was determined at 0, 24, 48 and 72 h by fluorimetric quantification. For assessment of the biological effects of EGF-coated Ti, gingival fibroblasts were seeded (5 × 104 cells) onto the substrate coated or not with this growth factor. After 24 h, cell adhesion and viability were evaluated by ANOVA and Tukey tests, α = .05. ResultsImmediate release of EGF as well as its incorporation by fibroblasts within 1 h after cells were seeded was observed. EGF-coated Ti discs presented significantly enhance surface roughness. Increased cell viability was observed on the EGF-coated discs. ConclusionEGF applied to Ti discs stimulated the adhesion and metabolism of gingival fibroblasts and could be considered as an interesting alternative for improving the BS.

In vitro Dermal Delivery of Epidermal Growth Factor Using Redox-responsive Cubosomes

Reduction-responsive monoolein (MO) cubosome was prepared for the dermal delivery of epidermal growth factor (EGF) by including cystamine-crosslinked alginate in the water channel of the cubosome. On atomic force micrograph, the cubosome was found as round particles and it was tens of nanometers in diameter. Additives such as alginate, cystamine, and EGF seemed to have little effect on the size and the shape of cubosome. The release of EGF from the cubosome was promoted by dithiothreitol (DTT, a reducing agent), possibly because the disulfide bond of the cross-linker (cystamine) might be broken by the reducing agent. The cubosome promoted the permeation of EGF through an artificial skin mounted on a diffusion cell. Thiazolyl blue tetrazolium bromide (MTT) assay revealed that the cubosome exhibited no marked cellular toxicity after it was incubated with cell (CCD-986sk) for 24 h as long as the concentration was not greater than 20 ug/mL. Free EGF could hardly promote the cell proliferation at all the concentrations tested (0.25 ppm–1 ppm). EGF contained in the cubosome suspension significantly enhanced cell proliferation when EGF concentration was 0.75 and 1 ppm. EGF contained in the cubosome suspension could maintain about 85% of the initial biological activity while it was stored at 25°C for 4 weeks.

Epidermal Growth Factor-Releasing Radially Aligned Electrospun Nanofibrous Patches for the Regeneration of Chronic Tympanic Membrane Perforations.

Chronic tympanic membrane (TM) perforations can cause otorrhea. To date, various types of tissue engineering techniques have been applied for the regeneration of chronic TM perforations. However, the application of nanofibers with radially aligned nanostructures and the simultaneous release of growth factors have never been applied in the regeneration of chronic TM perforations. Here, epidermal growth factor (EGF)-releasing radially aligned nanofibrous patches (ERA-NFPs) are developed and applied for the regeneration of chronic perforated TMs. First, radial alignments and the presence of EGF in the ERA-NFPs are analyzed. EGF is confirmed to be released from the ERA-NFPs until 8 weeks. In an in vitro study, cell viability assay, immunocytochemistry, and wound-healing assay indicate rational enhancement of healing by the combination of radial alignments and EGF release. The effect of ERA-NFPs on TM cells is revealed by quantitative real-time polymerase chain reaction. An in vivo animal study shows that the ERA-NFPs effectively stimulates the healing of the chronic TM perforations. The TMs healed by ERA-NFPs show histological properties similar to those of normal TMs. These results indicate that ERA-NFPs may be an efficient platform for the regeneration of chronic TM perforations, laying the foundation for nonsurgical treatments of chronic otitis media.

Development and Evaluation of Multistructured and Hierarchical Epidermal Growth Factor-Poly (<inline-formula> <tex-math notation="LaTeX">$\varepsilon$ </tex-math> </inline-formula>-Caprolactone) Scaffolds

In this paper, we separately fabricated the poly ( ε -caprolactone) (PCL) scaffolds containing epidermal growth factor (EGF) by using our-self fabricated electrospinning machine for tissue regeneration application. Several fundamental properties, including the dimensions, wettability, and EGF release profiles, of the fabricated EGF-PCL bead, fibrous, and multistructured scaffolds were characterized by using the scanning electron microscopy (SEM), contact angle goniometer, and vertical diffusion system. The EGF release profiles of three scaffolds were measured for 200 h, and the multistructured scaffold performed stable and long EGF release properties. Furthermore, the in vitro and in vivo experiments were conducted to evaluate the performance of three types of EGF-PCL scaffolds. The NIH-3T3 fibroblast cells were cultured on the scaffolds to study the effects of the released EGF by using the Alamar Blue Cell Viability Assays, fluorescence image analysis, and SEM. The animal experiment demonstrated that the multistructured EGF-PCL scaffold achieved 95% of the wound healing rate to the cut-damaged wounds after 16 days. Moreover, the histopathological skin tissue showed that the wound regenerated well after the treatment of the multistructured EGF-PCL scaffold. The developed multistructured EGF-PCL scaffold has a high potential for the wound healing applications.

Monoolein cubic phase containing alginate/cystamine gel for controlled release of epidermal growth factor

Monoolein (MO) cubic phase including alginate and cystamine in its water channel controlled the release of epidermal growth factor (EGF) by responding to changes in pH value and the reductive conditions of the release medium. The crosslinking degree of alginate gel with cystamine and the complex coacervation of alginate and EGF were investigated by using light scattering. TEM micrographs of cubic phases revealed MO bilayers along with water channels. Differential scanning calorimetry indicated that the cubic-to-hexagonal phase transition took place at 60.2 °C. Additives such as stearyl trimethyl ammonium chloride and cystamine decreased the transition temperature by a few to more than 10 °C. The release of EGF loaded in cubic phases was completed in 5 h and, thereafter, no significant additional release was observed. The release % of EGF loaded in MO cubic phase containing alginate and cystamine increased not only with the increase of pH but also glutathione concentration. The MO cubic phase containing alginate/cystamine gel can be used as a carrier for the delivery of peptide and protein drugs.

Collagen-based scaffold incorporated with PLGA microspheres for controlled epidermal growth factor release in skin tissue engineering

Collagen-based scaffold incorporated with PLGA microspheres for controlled epidermal growth factor release in skin tissue engineering

In Vitro and In Vivo Studies of a Collagen-Based Scaffold Carrying PLGA Microspheres for Sustained Release of Epidermal Growth Factor in Skin Regeneration

<i>In Vitro</i> and <i>In Vivo</i> Studies of a Collagen-Based Scaffold Carrying PLGA Microspheres for Sustained Release of Epidermal Growth Factor in Skin Regeneration

Preparation and properties of a novel carbon nanotubes/poly(vinyl alcohol)/epidermal growth factor composite biological dressing.

Wound dressings with drug delivery system have drawn increasing attention in skin damage recombination. Herein, a novel composite biological dressing was prepared and based on poly(vinyl alcohol) (PVA) combined with carbon nanotubes (CNTs) and epidermal growth factor (EGF) by electrospinning on gauze. The properties of the CNTs/PVA/EGF composite dressing were systemically investigated by general observation, and scanning electron microscopy (SEM). In vitro, the cytotoxicity of this dressing was investigated using a methyl thiazolyl tetrazolium (MTT) assay on L929 fibroblasts. In order to study the sustained release of EGF from this dressing, the concentration of EGF at different times was tested by ELISA. Furthermore, the biological activity of the released EGF was also evaluated using the MTT assay. Moreover, an in vivo experiment was conducted to observe whether this dressing was capable of improving healing in the model of wounded skin on rats. It was revealed that this dressing had a well-distributed microstructure by SEM. Additionally, the grade of cytotoxicity was low, and the EGF had a sustained release rate from this dressing. Furthermore, a maximum accumulative release rate of 12.47% was identified at 12 h, and was retained at 9.4% after 48 h. Simultaneously, the relative growth rate of L929 fibroblasts in the 12 h experimental group and 48 h group was 291.24 and 211.3%, respectively. Next, the efficacy of these products was evaluated in vivo using Sprague-Dawley rats with a skin injury model. The healing of wounded skin of rats was sped up by this dressing based on the gross and histological appearances. From 7 to 10 days, the wounds in the experimental group were almost healed. In conclusion, this CNTs/PVA/EGF dressing had a well-distributed structure and an ability to release EGF at a sustained rate with the activity being favorable. On the basis of those results, a positive influence of designed dressing for accelerated wound healing was confirmed.

Biologically Triggered Delivery of EGF from Polymer Fiber Patches.

Wound healing is modulated by complex spatial and temporal regulation of growth factors within a wound site. Regenerative medicine seeks to generate materials that can mimic this environment for the healing of chronic or traumatic wounds. Herein, we report a programmed release of epidermal growth factor (EGF) from coextruded polymer fiber patches, which is triggered by the natural biological cascade of wound healing. Genetically engineered EGF containing a matrix metalloproteinase (MMP) cleavage site was covalently conjugated to a nonwoven poly(ε-caprolactone) (PCL) fiber mat fabricated by multilayered melt coextrusion. The genetically modified EGF showed rapid release in the presence of a biological trigger, MMP-9, while a control protein showed negligible release. The biologically responsive fiber mat dramatically enhanced proliferation and migration of human keratinocytes in the presence of MMP-9. This study describes the release of a critical wound-healing growth factor as triggered by the biology inherent in the healing process.

Altered timing of riboflavin and ultraviolet light pathogen inactivation improves platelet in vitro quality.

The platelet (PLT) storage lesion is in part caused by the collection and/or production process. Pathogen inactivation (PI) further accelerates its development leading to a reduced in vitro PLT functionality and hence quality. Although the treatment of PLT concentrates (PCs) with riboflavin and ultraviolet light PI should occur within 22 hours of collection, in this study the impact of treatment timing on in vitro PLT quality was investigated. Apheresis PCs were PI treated on the day of production or on Days 1, 3, or 4 of storage or left untreated as control. A panel of in vitro variables was used to monitor quality throughout 7-day storage, including metabolism, PLT activation, and release of microparticles. Changes in phosphorylation profiles of proteins in the lysate and levels of PLT factor 4, thrombospondin, and epidermal growth factor (EGF) in the releasate were analyzed by immunoblots or enzyme-linked immunosorbent assay. By Day7 of storage, units illuminated on Day4 showed a smaller impact of the PI process than units treated on the day of production or one day after on PLT quality such as PLT activation; metabolic activity; microvesicle and EGF release; and phosphorylation of p38, ERK, and HSP27. PCs treated on Day3 of storage displayed an intermediate effect. The timing of PI treatment of PCs influences in vitro PLT quality. Based on these results, timing recommendations should be reconsidered. If PI is applied, inventory management in blood banks might improve with a more flexible collection and treatment regime.

EGF-Loaded Hyaluronic Acid Based Microparticles as Effective Carriers in a Wound Model

Epidermal growth factor (EGF) is widely recognized to be involved in the regenerative process, but only a few studies document its effect on acute wounds when EGF release is sustained over a period of time by encapsulation in an emulsion-based hydrogel. Among hydrogels, hyaluronic acid (HA) is a promising carrier because it is biodegradable and known to bind to the components of the Extracellular Matrix (ECM) which undergoes remodeling during regeneration. Coupled with EGF in microparticulates, it may serve to directly deliver the cytokine to the impaired ECM to stimulate cells for ECM remodeling. In this study, a very simple and effective way is demonstrated to produce EGF-conjugated HA microspheres for the purpose of targeted and sustained EGF delivery to damaged ECM in acute wounds. This approach is advantageous due to its simplicity which may serve to accelerate research in wound regeneration and relevant drug discovery.

Abstract 2272: Association of G-protein estrogen receptor (GPER) in primary breast cancer in Caucasian and Black women by tumor immunophenotype and menopausal status

Abstract Background: Assignment of breast cancer therapies is largely defined by immunohistochemical analyses that evaluate steroid hormone and growth factor receptor status in primary tumor biopsies. Patients whose tumors are devoid of these receptors have fewer treatment options, and poor survival. This outcome is more commonly measured among Black versus Caucasian patients, and in patients with intact ovarian function. The G-protein coupled estrogen receptor, GPER, holds significance for breast cancer biology and treatment as 17β-estradiol and ER antagonists trigger the release of epidermal growth factor (EGF)-ligands and GPER associates directly with clinicopathological factors that predict advanced disease. Experimental design: GPER was measured by immunohistochemical analysis and a semi-quantitative scoring method in 521 primary breast tumors obtained from the NCI Cooperative Breast Cancer Tissue Resource and the Nashville Breast Health Study, including tumor specimens derived from 389 Caucasian and 108 Black patients. GPER was correlated with disease progression variables and evaluated by race, menopausal status and tumor immunophenotype. Results: GPER is expressed in more than two-thirds of invasive breast carcinomas in this study with no difference observed between Caucasian and Black women (p = 0.69). Coexpression of GPER and ER was measured in less than half of all tumors (48%). Additionally, GPER is commonly expressed in ER-negative tumors (107/171; 62%) and in triple negative breast cancer (TNBC) (42/56; 75%) and did not differ by race for this newly defined measure of estrogen responsiveness (p = 0.42). Moreover, while ER-negative tumors are more common in pre- (79/153; 52%) versus postmenopausal women (92/336; 27%), GPER expression is not influenced by menopausal status. GPER is positively associated with tumor size (particularly in premenopausal women) in both studies, and with frank metastases at first diagnosis in the NCI population. No significant association was seen with nodal invasion. Survival data in NBHS patients found that women who died of breast cancer are more likely to have GPER-positive tumors than survivors. Conclusion: GPER is expressed in the majority of invasive breast tumors (&amp;gt; 60%) at diagnosis and is commonly retained in patients with ER-negative or triple-negative disease regardless of race or menopause. Unlike ER, which varies inversely with variables that predict advanced disease, GPER is positively associated with these same prognostic parameters. These data support GPER as an independent marker of estrogen responsiveness and breast cancer progression. Most importantly, our results suggest that GPER represents a promising therapeutic target since its expression is constant across multiple types of invasive breast cancer, including patients with TNBC and in tumors from pre- and postmenopausal women. Citation Format: Sandra L. Deming-Halverson, Carl Graeber, Jason Machan, Edmond Sabo, Wei Zheng, Edward J. Filardo. Association of G-protein estrogen receptor (GPER) in primary breast cancer in Caucasian and Black women by tumor immunophenotype and menopausal status. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2272.

Preparation of bioactive and antimicrobial PLGA membranes by magainin II/EGF functionalization

Development of dual functional materials that are capable of both reducing bacterial interaction and encouraging host tissue integration has gained importance in design of biomaterials. In this study, we prepared a bilayer poly (lactide co-glycolide) fibrous membrane with antibacterial and bioactive properties by electrospinning. The antibacterial layer was produced by covalent immobilization of antimicrobial peptide, Magainin II. The bioactive layer incorporating epidermal growth factor (EGF) molecules was subsequently electrospun on the antibacterial layer. The membranes were characterized by X-ray photoelectron spectroscopy, scanning electron microscopy and fluorescence microscopy. EGF release was detected by enzyme-linked immunosorbent assay. The antibacterial activity was tested against Escherichia coli (E. coli) and Staphylococcus aureus (S. aureus). The ability to support tissue cell integration was detected by using L-929 mouse fibroblasts. The dual functional membranes established enhanced antibacterial properties and increased tissue cell compatibility. This combined approach suggests a promising strategy for wound dressings, vascular grafts and dental membranes as well as catheters and fixation devices.

Layer-by-layer polysaccharide-coated liposomes for sustained delivery of epidermal growth factor

A three-dimensional layer-by-layer (LbL) structure composed by xanthan and galactomannan biopolymers over dioctadecyldimethylammonium bromide (DODAB) liposome template was proposed and characterized for protein drug delivery. The polymers and the surfactant interaction were sufficiently strong to create a LbL structure up to 8 layers, evaluated using quartz crystal microbalance (QCM) and zeta potential analysis. The polymer–liposome binding enthalpy was determined by isothermal titration calorimetry (ITC). The bilayer of biopolymer-coated liposomes with diameters of 165 (±15)nm, measured by dynamic light scattering (DLS), and ζ-potential of −4 (±13)mV. These bilayer-coated nanoparticles increased up to 5 times the sustained release of epidermal growth factor (EGF) at a first order rate of 0.005min−1. This system could be useful for improving the release profile of low-stability drugs like EGF.

Wound Healing Effects of Rose Placenta in a Mouse Model of Full-Thickness Wounds

BackgroundRosa damascena, a type of herb, has been used for wound healing in Eastern folk medicine. The goal of this study was to evaluate the effectiveness of rose placenta from R. damascena in a full-thickness wound model in mice.MethodsSixty six-week-old C57BL/6N mice were used. Full-thickness wounds were made with an 8-mm diameter punch. Two wounds were made on each side of the back, and wounds were assigned randomly to the control and experimental groups. Rose placenta (250 µg) was injected in the experimental group, and normal saline was injected in the control group. Wound sizes were measured with digital photography, and specimens were harvested. Immunohistochemical staining was performed to assess the expression of epidermal growth factor (EGF), vascular endothelial growth factor (VEGF), transforming growth factor-β1 (TGF-β1), and CD31. Vessel density was measured. Quantitative analysis using an enzyme-linked immunosorbent assay (ELISA) for EGF was performed. All evaluations were performed on postoperative days 0, 2, 4, 7, and 10. Statistical analyses were performed using the paired t-test.Results On days 4, 7, and 10, the wounds treated with rose placenta were significantly smaller. On day 2, VEGF and EGF expression increased in the experimental group. On days 7 and 10, TGF-β1 expression decreased in the experimental group. On day 10, vessel density increased in the experimental group. The increase in EGF on day 2 was confirmed with ELISA.ConclusionsRose placenta was found to be associated with improved wound healing in a mouse full-thickness wound model via increased EGF release. Rose placenta may potentially be a novel drug candidate for enhancing wound healing.

A tubular gelatin scaffold capable of the time-dependent controlled release of epidermal growth factor and mitomycin C

A tubular gelatin scaffold for the time-dependent controlled release of epidermal growth factor (EGF) and mitomycin C (MMC) was fabricated. EGF was incorporated using silk fibroin carriers, and MMC was planted using polylactide (PLA) microspheres. The relationship between scaffold properties and crosslinking degrees was evaluated. As the crosslinking degree was increased from 23.7% to 65.3%, the mechanical properties of the scaffold obviously improved, and the compressive modulus increased to approximately 65kPa. The mass degradation of the scaffold was also controlled from 9 days to approximately 1 month. In vitro release tests indicated that the scaffold mainly released EGF in the early period and MMC in the later period. Urethral epithelial cells (UECs) and urethral scar derived fibroblast cells (UFCs) were coseeded in the scaffold at a ratio of 1:1. After 9 days of coculture, immunostaining results displayed that the proportion of UECs continuously increased to approximately 71%. These changes in cell proportion were confirmed by the results of Western blot analysis. Therefore, the scaffold promoted the growth but inhibited the regeneration of UFCs. This scaffold for time-dependent controlled release of multiple biofactors may be potentially useful in urethral reconstruction and other tissue engineering studies.

Evaluation of emulsion electrospun polycaprolactone/hyaluronan/epidermal growth factor nanofibrous scaffolds for wound healing.

Wound healing scaffolds provide cells with structural integrity and can also deliver biological agents to establish a skin tissue-specific microenvironment to regulate cell functions and to accelerate the healing process. In this study, we fabricated biodegradable nanofibrous scaffolds with an emulsion electrospinning technique. The scaffolds were composed of polycaprolactone, hyaluronan and encapsulating epidermal growth factor. The morphology and core-sheath structure of the nanofibers were characterized by scanning electron microscopy and transmission electron microscopy. The scaffolds were also characterized for chemical composition and hydrophilicity with a Fourier-transform infrared analysis, energy dispersive spectroscopy and the water contact angle. An invitro model protein bovine serum albumin and epidermal growth factor release study was conducted to evaluate the sustained release potential of the core-sheath structured nanofibers with and without the hyaluronan component. Additionally, an invitro cultivation of human skin keratinocytes (HaCaT) and fibroblasts on polycaprolactone/hyaluronan and polycaprolactone/hyaluronan-epidermal growth factor scaffolds showed a significant synergistic effect of hyaluronan and epidermal growth factor on cell proliferation and infiltration. Furthermore, there was an up-regulation of the wound-healing-related genes collagen I, collagen III and TGF-β in polycaprolactone/hyaluronan/epidermal growth factor scaffolds compared with control groups. In the full-thickness wound model, the enhanced regeneration of fully functional skin was facilitated by epidermal regeneration in the polycaprolactone/hyaluronan/epidermal growth factor treatment group. Our findings suggest that bioactivity and hemostasis of the hyaluronan-based nanofibrous scaffolds have the capability to encapsulate and control the release of growth factors that can serve as skin tissue engineering scaffolds for wound healing.