Light‐Controlled Growth Factors Release on Tetrapodal ZnO‐Incorporated 3D‐Printed Hydrogels for Developing Smart Wound Scaffold

Abstract

Advanced wound scaffolds that integrate active substances to treat chronic wounds have gained significant recent attention. While wound scaffolds and advanced functionalities have previously been incorporated into one medical device, the wirelessly triggered release of active substances has remained the focus of many research endeavors. To combine multiple functions including light-triggered activation, antiseptic, angiogenic, and moisturizing properties, a 3D printed hydrogel patch encapsulating vascular endothelial growth factor (VEGF) decorated with photoactive and antibacterial tetrapodal zinc oxide (t-ZnO) microparticles is developed. To achieve the smart release of VEGF, t-ZnO is modified by chemical treatment and activated through ultraviolet/ visible light exposure. This process would also make the surface rough and improve protein adhesion. The elastic modulus and degradation behavior of the composite hydrogels, which must match the wound healing process, are adjusted by changing t-ZnO concentrations. The t-ZnO-laden composite hydrogels can be printed with any desired micropattern to potentially create a modular elution of various growth factors. The VEGF-decorated t-ZnO-laden hydrogel patches show low cytotoxicity and improved angiogenic properties while maintaining antibacterial functions in vitro. In vivo tests show promising results for the printed wound patches, with less immunogenicity and enhanced wound healing.

Rational Design and Preparation of Functional Hydrogels for Skin Wound Healing

“…Therefore, loading growth factors or peptides that promote angiogenesis in hydrogels has become a feasible strategy. For example, Siebert et al (2021) developed a 3D printing hydrogel patch coated with VEGF and modified by tetrapod zinc oxide (t-ZnO) particles with photoactivity and antibacterial effect. The controlled release of VEGF could be achieved by chemical modification of t-ZnO and activation with ultraviolet/visible light.…”

Mechanisms and applications of bioinspired underwater/wet adhesives

“…Recently, various functional hydrogels have been widely used to promote wound healing. [108][109][110][111][112][113][114][115][116][117][118] Chang and coworkers developed a unique bioglass (BG)/oxidized sodium alginate (OSA) composite hydrogel that showed excellent bioactivity to promote vascularization and accelerate tissue regeneration. 119 On the one hand, the BG improves the tissue bonding strength by providing an alkaline microenvironment to stimulate bond formation between the OSA and the amino groups on the surrounding tissue.…”

3D-Printed Products for Topical Skin Applications: From Personalized Dressings to Drug Delivery

“…Stimuli-responsive delivery systems are smart approaches for the controlled and sitespecific release of molecules [168]. Siebert et al (2021) proposed a multifunctional wound hydrogel patch containing VEGF decorated with photoactive tetrapodal zinc oxide and activated through ultraviolet/visible light stimulus. The stimulus-responsive system provided controlled release of VEGF with green light exposure over 120 s. Two concentrations of VEGF were studied and the release rate was not affected by VEGF concentration.…”

“…Additionally, tetrapodal zinc oxide features antimicrobial activity, which is important to the adequate wound healing process, in agreement with the in vitro antibacterial assays. The in vivo studies of the wound healing model showed that the 3D-printed scaffold with tetrapodal zinc oxide and VEGF promoted faster wound healing, by enhanced anti-inflammatory, angiogenesis and cell proliferation effects [151].…”