Release Of Epidermal Growth Factor Research Articles

Bioluminescence Resonance Energy Transfer (BRET)-Mediated Protein Release from Self-Illuminating Photoresponsive Biomaterials.

Phototriggered release of various cargos, including soluble protein factors and small molecules, has the potential to correct aberrant biological events by offering spatiotemporal control over local therapeutic levels. However, the poor penetration depth of light historically limits implementation to subdermal regions, necessitating alternative methods of light delivery to achieve the full potential of photodynamic therapeutic release. Here, we introduce a strategy exploiting bioluminescence resonance energy transfer (BRET)-an energy transfer process between light-emitting Nanoluciferase (NLuc) and a photosensitive acceptor molecule-to drive biomolecule release from hydrogel biomaterials. Through a facile, one-pot, and high-yielding synthesis (60-70%), we synthesized a heterobifunctional ruthenium cross-linker bearing an aldehyde and an azide (CHO-Ru-N3), a compound that we demonstrate undergoes predictable exchange of the azide-bearing ligand under blue-green light irradiation (>550 nm). Following site-specific conjugation to NLuc via sortase-tag enhanced protein ligation (STEPL), the modified protein was covalently attached to a poly(ethylene glycol) (PEG)-based hydrogel via strain-promoted azide-alkyne cycloaddition (SPAAC). Leveraging the high photosensitivity of Ru compounds, we demonstrate rapid and equivalent release of epidermal growth factor (EGF) via either direct illumination or via BRET-based bioluminolysis. As NLuc-originated luminescence can be controlled equivalently throughout the body, we anticipate that this unique protein release strategy will find use for locally triggered drug delivery following systemic administration of a small molecule.

NIR‐Responsive Multifunctional Artificial Skin for Regenerative Wound Healing

AbstractEfficient wound repair with skin appendage regeneration following severe trauma poses a challenge due to the scarcity of skin grafts and decreased drug effectiveness in protease‐rich wound microenvironments. Here, a multifunctional artificial skin (NIR‐mFAS) with photothermal‐triggered drug delivery capabilities is designed to actively and comprehensively improve the regenerative potential of full‐thickness wounds. The antibacterial chitosan/silk fibroin hydrogel matrix of artificial skin, cross‐linked by electrostatic interactions, effectively encapsulates and sustains the release of epidermal growth factor (EGF) to accelerate re‐epithelialization and neovascularization by promoting the migration and proliferation of repair cells. Subsequently, the photothermal responsive polydopamine nanoparticles (PDA‐NPs) dispersed in the matrix enable precise control over the release of BMP4 under the irradiation of 1064 nm NIR, thereby inhibiting scarring by reducing myofibroblasts during the proliferative stage. Importantly, the concurrent controlled release of CHIR99021 can modulate cell fate by inducing the conversion of myofibroblasts into dermal papilla‐like cells, leading to hair follicle and sebaceous gland regeneration. The NIR‐mFAS functions as an advanced delivery system for achieving high‐quality wound healing with appendage regeneration and offers a smart therapeutic approach that can be applied to other treatments requiring coordinated delivery of multiple pharmacological agents.

The combined effect of epidermal growth factor and keratinocyte growth factor delivered by hyaluronic acid hydrogel on corneal wound healing

This study strategically incorporates epidermal growth factor (EGF) and keratinocyte growth factor (KGF) within a hyaluronic acid (HA) hydrogel to enhance corneal wound healing. The controlled release of EGF and KGF from the HA hydrogel is engineered to promote the regeneration of both the epithelial and stromal layers. Specifically, EGF plays a pivotal role in the regeneration of the epithelial layer, while KGF exhibits efficacy in the regeneration of the stromal layer. The combination of these growth factors facilitates efficient regeneration of each layer and demonstrates the capability to modulate each other's regenerative effects. The interplay between EGF and KGF provides an understanding of their cooperative influence on the dynamics of corneal wound healing. The results of this study contribute to the development of advanced strategies for corneal wound management and offer insights into the complex process of corneal regeneration.

Development of Thiol-Ene Reaction-Based HA Hydrogel with Sustained Release of EGF for Enhanced Skin Wound Healing.

This study develops a novel drug delivery system using a hyaluronic acid (HA) hydrogel for controlled release of epidermal growth factor (EGF) to enhance skin wound healing. Conventional hydrogel-based methods suffer from a burst release and limited drug delivery times. To address this, we employ bioconjugation to introduce an acrylate group to EGF, enabling chemical bonding to the HA hydrogel matrix through thiol-ene cross-linking. This approach results in sustained-release delivery of EGF based on the degradation rate of the HA matrix, overcoming diffusion-based limitations. We confirm the introduction of the acrylate group using matrix-assisted laser desorption ionization-time-of-flight (MALDI-TOF) mass spectrometry. We evaluated the hydrogel morphology and rheological properties following binding of acrylate-conjugated EGF to the HA matrix. Assessment of the EGF release profile demonstrates delayed release compared to unconjugated EGF. We evaluate the impact on cells through cell proliferation and scratch assays, indicating the system's efficacy. In a rat wound healing model, the sustained release of EGF from the hydrogel system promotes appropriate tissue healing and restores it to a normal state. These findings suggest that this practical drug delivery system, involving the modification of growth factors or drugs to chemically bind healing factors to hydrogels, can achieve long-lasting effects.

Hyaluronic acid hydrogel for controlled release of heterobifunctional photocleavable linker-modified epidermal growth factor in wound healing

Peptide and protein drugs, such as epidermal growth factor (EGF), face challenges related to stability and bioavailability. Recently, hydrogels have emerged as promising carriers for these drugs. This study focuses on a light-responsive hydrogel-based drug delivery system for the controlled release of EGF in wound healing. A photocleavable (PC) linker was designed to bind EGF to the hydrogel matrix, enabling UV light-triggered release of EGF. Hydrogels have evolved from drug reservoirs to controlled release systems, and the o-nitrobenzyl-based PC linkers offer selective cleavage under UV irradiation. We used a thiol-ene crosslinked hyaluronic acid (HA) hydrogel matrix modified with the PC-linked EGF. The release of EGF from the HA hydrogel under UV irradiation was evaluated, along with in vitro and in vivo experiments to assess the controlled effect of EGF on wound healing. Our results indicate that the successful development of a light-responsive hydrogel-based system for precise temporal release of EGF enhances the therapeutic potential in wound healing. This study highlights the importance of incorporating stimulus-responsive functionalities into hydrogel-based drug delivery systems to optimize protein drugs in clinical applications.

Chitosan Resin-Modified Glass Ionomer Cement Containing Epidermal Growth Factor Promotes Pulp Cell Proliferation with a Minimum Effect on Fluoride and Aluminum Release.

The development of biomaterials that are able to control the release of bioactive molecules is a challenging task for regenerative dentistry. This study aimed to enhance resin-modified glass ionomer cement (RMGIC) for the release of epidermal growth factor (EGF). This RMGIC was formulated from RMGIC powder supplemented with 15% (w/w) chitosan at a molecular weight of either 62 or 545 kDa with 5% bovine serum albumin mixed with the same liquid component as the Vitrebond. EGF was added while mixing. ELISA was used to determine EGF release from the specimen immersed in phosphate-buffered saline at 1 h, 3 h, 24 h, 3 d, 1 wk, 2 wks, and 3 wks. Fluoride and aluminum release at 1, 3, 5, and 7 d was measured by electrode and inductively coupled plasma optical emission spectrometry. Pulp cell viability was examined through MTT assays and the counting of cell numbers using a Coulter counter. The RMGIC with 65 kDa chitosan is able to prolong the release of EGF for significantly longer than RMGIC for at least 3 wks due to its retained bioactivity in promoting pulp cell proliferation. This modified RMGIC can prolong the release of fluoride, with a small amount of aluminum also released for a limited time. This biomaterial could be useful in regenerating pulp-dentin complexes.

In Vitro and In Vivo Evaluation of Epidermal Growth Factor (EGF) Loaded Alginate-Hyaluronic Acid (AlgHA) Microbeads System for Wound Healing.

The management of skin injuries is one of the most common concerns in medical facilities. Different types of biomaterials with effective wound-healing characteristics have been studied previously. In this study, we used alginate (Alg) and hyaluronic acid (HA) composite (80:20) beads for the sustained release of epidermal growth factor (EGF) delivery. Heparin crosslinked AlgHA beads showed significant loading and entrapment of EGF. Encapsulated beads demonstrated biocompatibility with rat L929 cells and significant migration at the concentration of AlgHAEGF100 and AlgHAEGF150 within 24 h. Both groups significantly improved the expression of Fetal Liver Kinase 1 (FLK-1) along with the Intercellular Adhesion Molecule-1 (ICAM-1) protein in rat bone Mesenchymal stem cells (rbMSCs). In vivo assessment exhibited significant epithelialization and wound closure gaps within 2 weeks. Immunohistochemistry shows markedly significant levels of ICAM-1, FLK-1, and fibronectin (FN) in the AlgHAEGF100 and AlgHAEGF150 groups. Hence, we conclude that the EGF-loaded alginate-hyaluronic acid (AlgHA) bead system can be used to promote wound healing.

EGF, a veteran of wound healing: highlights on its mode of action, clinical applications with focus on wound treatment, and recent drug delivery strategies

Epidermal growth factor (EGF) has been used in wound management and regenerative medicine since the late 1980s. It has been widely utilized for a long time and still is because of its excellent tolerability and efficacy. EGF has many applications in tissue engineering, cancer therapy, lung diseases, gastric ulcers, and wound healing. Nevertheless, its in vivo and during storage stability is a primary concern. This review focuses on the topical use of EGF, especially in chronic wound healing, the emerging use of biomaterials to deliver it, and future research possibilities. To successfully deliver EGF to wounds, a delivery system that is proteolytically resistant and stable over the long term is required. Biomaterials are an area of interest for the development of such systems. These systems may be used in non-healing wounds such as diabetic foot ulcers, pressure ulcers, and burns. In these pathologies, EGF can reduce the risk of amputation of the lower extremities, as it accelerates the wound healing process. Furthermore, appropriate delivery system would also stabilize and control the EGF release profile in a wound. Several in vitro and in vivo studies have already proven the efficacy of such systems in the above-mentioned types of wounds. Moreover, several formulations such as ointments and intralesional injections are already available on the market. However, these products are still problematic in terms of inadequate diffusion of EGF, low bioavailability storage conditions, and shelf-life. This review discusses the nano formulations comprising biomaterials infused with EGF which could be a promising delivery system for chronic wound healing in the future.

Epidermal growth factor-loaded microspheres/hydrogel composite for instant hemostasis and liver regeneration

Rapid hemostasis and effective healing for the non-compressible liver wounds which are not able to be sewn, especially for those large-area wounds, remain great clinical challenges. In this study, we fabricated epidermal growth factor (EGF)-loaded chitosan microspheres (CM) and then incorporated them into a photo-crosslinking gelatin methacryloyl (GelMA) hydrogel. The results showed that the EGF-loaded CM/GelMA precursor solution could transform into a hydrogel and cease bleeding at laceration sites without external stress. Subsequently, the sustained release of EGF accelerated wound closure and promoted liver regeneration. The in vitro experiments demonstrated that the microsphere/hydrogel composite could promote the proliferation and migration of L02 ​cells. Moreover, the histological and immunohistological analyses indicated that EGF-CM/GelMA composite could alleviate inflammation in the mouse liver and promote liver remodeling. Overall, this multi-functional microsphere/hydrogel composite will inspire the development of clinical applications for noncompressible hemostasis and successive wound closure.

Hypoxic pulmonary endothelial cells release epidermal growth factor leading to vascular smooth muscle cell arginase-2 expression and proliferation.

The hallmark of pulmonary hypertension (PH) is vascular remodeling. We have previously shown that human pulmonary microvascular endothelial cells (hPMVEC) respond to hypoxia with epidermal growth factor (EGF) mediated activation of the receptor tyrosine kinase, EGF receptor (EGFR), resulting in arginase‐2 (Arg2)‐dependent proliferation. We hypothesized that the release of EGF by hPMVEC could result in the proliferation of human pulmonary arterial smooth muscle cells (hPASMC) via activation of EGFR on the hPASMC leading to Arg2 up‐regulation. To test this hypothesis, we used conditioned media (CM) from hPMVEC grown either in normoxia (NCM) or hypoxia (HCM). Human PASMC were incubated in normoxia with either HCM or NCM, and HCM caused significant induction of Arg2 and viable cell numbers. When HCM was generated with either an EGF‐neutralizing antibody or an EGFR blocking antibody the resulting HCM did not induce Arg2 or increase viable cell numbers in hPASMC. Adding an EGFR blocking antibody to HCM, prevented the HCM‐induced increase in Arg2 and viable cell numbers. HCM induced robust phosphorylation of hPASMC EGFR. When hPASMC were transfected with siRNA against EGFR the HCM‐induced increase in viable cell numbers was prevented. When hPASMC were treated with the arginase antagonist nor‐NOHA, the HCM‐induced increase in viable cell numbers was prevented. These data suggest that hypoxic hPMVEC releases EGF, which activates hPASMC EGFR leading to Arg2 protein expression and an increase in viable cell numbers. We speculate that EGF neutralizing antibodies or EGFR blocking antibodies represent potential therapeutics to prevent and/or attenuate vascular remodeling in PH associated with hypoxia.

Controlled Release of Epidermal Growth Factor from Furfuryl-Gelatin Hydrogel Using in Situ Visible Light-Induced Crosslinking and Its Effects on Fibroblasts Proliferation and Migration.

Hydrogels are widely used in tissue engineering as materials that regulate cell proliferation, migration, and differentiation. They also act as promising biomaterials that can provide a variety of stimuli by influencing the surrounding microenvironment, which can be achieved by modulating their mechanical properties, thereby aiding soluble factor delivery. Here, we developed a gelatin-based injectable hydrogel that has controllable mechanical properties and demonstrates sustained drug release without the need for invasive surgery. Gelatin was modified with furfuryl groups, and riboflavin phosphate was used as a photoinitiator to crosslink the hydrogel using visible light. A hydrogel–with a storage modulus in the range of 0.2–15 kPa was formed by maintaining the concentration of furfuryl-gelatin within 10–30% w/v. Consequently, their mechanical properties can be tailored for their applications. The furfuryl-gelatin hydrogel was loaded with maleimide-modified epidermal growth factor (EGF) as a model drug to achieve a controlled-release system. The sustained release of maleimide-EGF due to gelatin hydrogel matrix degradation was observed. Cell proliferation and scratch assays were performed to verify its effect on fibroblasts. When EGF was physically entrapped in the hydrogel matrix, the released EGF considerably affected cell proliferation and scratch closure of fibroblasts at the beginning of the culture. By contrast, maleimide-EGF was released sustainably and steadily and affected cell proliferation and scratch closure after the initial stage. We demonstrated that the release of soluble factors could be controlled by modulating the mechanical properties. Thus, the injectable hydrogel formed by in situ visible light-induced crosslinking could be a promising biomaterial for tissue engineering and biomedical therapeutics.

To Study the Efficacy of Placental Extract Gel in Chronic Non Healing Foot Ulcer

Wound healing is a complex and regulated process that is critical in maintaining the skin barrier function. The numerous disease processes can affect the events involved in wound healing, resulting in chronic, non-healing wounds. These would subject them to significant discomfort and distress and drain the medical system resources enormously. A chronic wound can be defined as that does not heal in an orderly set of stages and in a predictable amount of time or within three months. They remain in the inflammatory phase for too longand never heal or may take years.3,4 Chronic leg and foot ulcers occur in many adults with diabetes, chronic venous insufficiency, arterial disease, prolonged pressure, or neuropathy.5 Chronic ulcers may last for 12 to 13 months and even recur in 60-70% of cases. They cause loss of function and decreased quality of life and significant morbidity.6,7 These chronic ulcers are predominantly seen in elderly, becoming more prevalent and more difficult to treat and are associated with high treatment costs. So wound care has become essential in these ulcers, and surgical debridement and dressings are the corners stones. Many wound dressings like gauge, films, hydrocolloids, gels, foams etc. were developed to both protect the healing wound from infection and to promote the healing process.1 Placental extract gel is a rich source of various peptides, amino acids, nucleotides, PDRNs and carbohydrates, which are believed to support the healing process.9 Application of placental extract preparation increases collagen synthesis, increases tissue protein, accelerates neoangiogenesis, and epithelialization.10 It has an immunotropic effect and causes the release of Epidermal growth factor, Fibroblast growth factor at the tissue level. It also reduces surrounding tissue inflammation and oedema and reduces microbial burden.11 Its application accelerates healing because of amino acids, nucleotide and vitamins that improve healing.

Retraction Note to: Decellularized scaffolds containing hyaluronic acid and EGF for promoting the recovery of skin wounds

There is no effective therapy for the treatment of deep and large area skin wounds. Decellularized scaffolds can be prepared from animal tissues and represent a promising biomaterial for investigation in tissue regeneration studies. In this study, MTT assay showed that epidermal growth factor (EGF) increased NIH3T3 cell proliferation in a bell-shaped dose response, and the maximum cell proliferation was achieved at a concentration of 25 ng/ml. Decellularized scaffolds were prepared from pig peritoneum by a series of physical and chemical treatments. Hyaluronic acid (HA) increased EGF adsorption to the scaffolds. Decellularized scaffolds containing HA sustained the release of EGF compared to no HA. Rabbits contain relatively large skin surface and are less expensive and easy to be taken care, so that a rabbit wound healing model was use in this study. Four full-thickness skin wounds were created in each rabbit for evaluation of the effects of the scaffolds on the skin regeneration. Wounds covered with scaffolds containing either 1 or 3 μg/ml EGF were significantly smaller than with vaseline oil gauzes or with scaffolds alone, and the wounds covered with scaffolds containing 1 μg/ml EGF recovered best among all four wounds. Hematoxylin-Eosin staining confirmed these results by demonstrating that significantly thicker dermis layers were also observed in the wounds covered by the decellularized scaffolds containing HA and either 1 or 3 μg/ml EGF than with vaseline oil gauzes or with scaffolds alone. In addition, the scaffolds containing HA and 1 μg/ml EGF gave thicker dermis layers than HA and 3 μg/ml EGF and showed the regeneration of skin appendages on day 28 post-transplantation. These results demonstrated that decellularized scaffolds containing HA and EGF could provide a promising way for the treatment of human skin injuries.

An intrinsically bioactive hydrogel with on-demand drug release behaviors for diabetic wound healing

Prolonged, intense inflammation and excessive oxidative stress hinder diabetic wounds from healing normally, leading to disorders downstream including the postponement of re-epithelialization and extracellular matrix (ECM) formation. Herein, we report a hyaluronic acid (HA) and chitosan based hydrogel (OHA-CMC) with inherent antibacterial and hemostatic activities fabricated via Schiff base reaction. By encapsulating nanotechnologically-modified curcumin (CNP) and epidermal growth factor (EGF) into the hydrogel, OHA-CMC/CNP/EGF exhibited extraordinary antioxidant, anti-inflammatory, and migration-promoting effects in vitro. Meanwhile, OHA-CMC/CNP/EGF presented on-demand drug release in synchrony with the phases of the wound healing process. Specifically, curcumin was rapidly and constantly released to alleviate inflammation and oxidative stress in the early phase of wound healing, while a more gradual and sustained release of EGF supported late proliferation and ECM remodeling. In a diabetic full-thickness skin defect model, OHA-CMC/CNP/EGF dramatically improved wound healing with ideal re-epithelialization, granulation tissue formation, and skin appendage regeneration, highlighting the enormous therapeutic potential this biomaterial holds as a diabetic wound dressing.

Novel chitosan-ulvan hydrogel reinforcement by cellulose nanocrystals with epidermal growth factor for enhanced wound healing: In vitro and in vivo analysis

Several dressing materials can be used efficiently in recent times, both in their natural and synthetic combinations like; microfibers, film, nanofibers, hydrogels, and various drugs. The specific characteristics, such as biocompatibility and providing a favorable environment for wound healing, make many polysaccharides pivotal as wound dressings. Keeping in view the importance of these polysaccharides, we have developed novel chitosan-ulvan hydrogel incorporated by cellulose nanocrystals (CNCs) loading epidermal growth factor (EGF) drug (CS-U-CNC-EGF) by the freeze-dried process. The morphological features of novel hydrogel were perceived by FTIR, XRD, FESEM, and DSC analysis. The incorporation of the nanocrystals content modified the porous microstructure at pore size from 237 ± 59 μm to 53 ± 16 μm, improved mechanical stress curve from 0.57 MPa to 1.2 MPa, thermal and swelling behavior. The novel nanocomposites revealed non-toxic behavior and excellent cell proliferation. Whereas hydrogel showed sustained release of the epidermal growth factor (EGF), thereby enhancing EGF delivery at the wound site for 15 days from a 100% wound contraction treated group. Moreover, the controlled release of EGF from CS-U-CNC-EGF hydrogels showed significantly faster-wound healing efficiency concerning considerably faster granulations tissue formation and collagen deposition. The study's results point to possible future applications of this composite hydrogel in wound healing as a wound dressing material.

Spatially heterogeneous epidermal growth factor release from microporous annealed particle (MAP) hydrogel for improved wound closure.

Microporous annealed particle (MAP) hydrogel has been a promising scaffold platform technology to promote immediate tissue integration in injured tissue environments. The addition of growth factors has the potential to accelerate tissue integration and enhance scaffold-mediated healing. Growth factor releasing scaffolds face the translational hurdle of limited solubilized protein shelf stability; however, to address this hurdle we present a lyophilized MAP scaffold which can be effectively rehydrated directly prior to use. Our new approach includes a heterogenous MAP scaffold wherein 5% of the microgels contain immobilized heparin loaded with epidermal growth factor (EGF) at 1 μg mL-1. We demonstrate that these scaffolds, which are directly loaded with EGF following lyophilization maintain equivalent properties to scaffolds loaded passively via diffusion into water-swollen microgels, including EGF release profiles and cell migration studies that did not significantly differ. Further, these heterogeneous scaffolds exhibit a significant increase in cellular migration in vitro and quicker re-epithelialization in vivo. This progress on spatially heterogenous growth factor release from MAP scaffolds has great potential to improve complex wound treatment and advance the field of growth factor releasing scaffolds.

A Multi-Donor Ex Vivo Platelet Activation and Growth Factor Release Study Using Electric Pulses With Durations Up to 100 Microseconds

In vitro platelet activation is established in various clinical settings for wound healing and tissue regeneration. After separating platelet rich plasma (PRP) from whole blood, a biochemical activator, typically bovine thrombin (BT), is applied to activate PRP, which clots the PRP and releases growth factors beneficial for wound healing. BT’s drawbacks, particularly cost, availability, workflow challenges, and potential immune responses, motivated the development of ex vivo electrical activation of PRP using pulsed electric fields (PEFs) with durations on the order of hundreds of nanoseconds and electric field strengths from $\sim 10$ -100 kV/cm. PEFs permeabilize platelets to facilitate Ca2+ transport into the cells to induce platelet activation; however, membrane permeabilization does not require PEFs of such short duration and high intensity. This study demonstrates that 5- $100~\mu \text{s}$ duration PEFs effectively activate platelets. Treating PRP with ten different single pulse waveforms with durations between 5 and $100~\mu \text{s}$ induces similar or higher levels of platelet derived, vascular endothelial, and epidermal growth factor release compared to BT. These results indicate the potential clinical relevance of microsecond PEFs for platelet stimulation, which may reduce the expense and device footprint for PEF mediated platelet stimulation compared to nanosecond pulse generators, facilitating technology transition for clinical and trauma applications.

Spatiotemporally Controlling the Release of Biological Effectors Enhances Their Effects on Cell Migration and Neurite Outgrowth.

It is a major challenge to coordinate topographic cues from scaffolds with the on-demand, sustained release of biological effectors to maximize their performance in tissue regeneration. Here, a system involving masked, photo-triggered release of biological effectors from a temperature-sensitive scaffold for augmented cell migration and neurite outgrowth is reported. The scaffold contains microparticles of a phase-change material (PCM) sandwiched between two layers of electrospun fibers. The biological effectors are co-loaded with a photothermal dye in the PCM microparticles. Under irradiation with a near-infrared laser, the PCM will be melted to swiftly release the biological effectors. By imposing a photomask between the scaffold and the laser, only those microparticles in the irradiated region are melted, enabling a spatial control over the release. By adjusting the photomask, different regions of the scaffold can be sequentially irradiated at designated times, realizing on-demand and sustained release of the biological effectors with spatiotemporal controls. In one demonstration, this method is used to accelerate the directional migration of NIH-3T3 fibroblasts along the uniaxial or radial direction of fiber alignment by controlling the release of epidermal growth factor. In another demonstration, the release of nerve growth factor is managed to significantly promote neurite outgrowth from PC12 cells.

Modulation of Epidermal Growth Factor Release by Biopolymer-Coated Liposomes

This work describes the development of polysaccharide-coated liposomes to modulate the delivery of epidermal growth factor (EGF), with the aim to produce different EGF release profiles depending on the milieu of infected wounds. For this purpose, cationic liposomes were coated with one layer of sodium alginate (ALG) followed by one layer of chitosan (CHI) using the layer-by-layer (LbL) technique. The coated liposomes exhibited apparent hydrodynamic diameters of 278 ± 36 and 216 ± 96 nm for Lip-ALG and Lip-ALG-CHI, respectively. Thus, it appears that adding the CHI layer compacted the Lip-ALG one. The incorporation efficiency of EGF was a maximum of 55% for liposomes with a polymeric coating. In vitro release experiments showed that Lip-ALG-CHI exhibits a higher release rate constant under acidic pH conditions, resembling those of infected tissue. Using an ex vivo model of EGF release in porcine ear skin, these liposomes were found to accumulate in the epidermis. Thus, coated liposomes could represent a local EGF delivery mechanism to promote healing.

Photo-responsive supramolecular hyaluronic acid hydrogels for accelerated wound healing

Supramolecular hydrogels confer control over structural properties in a reversible, dynamic, and biomimetic fashion. The design of supramolecular hydrogels with an improved structural and functional recapitulation of damaged organs is important for clinical applications. For wound healing management, in particular, an effective healing process, through the modulation of epidermal growth factor (EGF) delivery using supramolecular polysaccharide hydrogels, has yet to be developed. In this study, photo-responsive supramolecular polysaccharide hydrogels were formed through host-guest interactions between azobenzene and β-cyclodextrin groups conjugated to hyaluronic acid chains. By exploiting the photoisomerization properties of azobenzene under different wavelengths, a supramolecular hydrogel featuring a dynamic spatial network crosslink density through the application of a light stimulus was obtained. Under ultra violet (UV) light, the loosened hydrogel can rapidly release EGF, thereby enhancing EGF delivery at the wound site. Based on an in vivo assessment of the healing process through a full-thickness skin defect model, the controlled EGF release from a supramolecular hydrogel exhibited superior wound healing efficiency with respect to granulation tissue formation, growth factor levels, and angiogenesis. Therefore, the proposed supramolecular hydrogels are potentially valuable as controlled delivery systems for future clinical wound healing applications.