Martina Žabčić

Interface-engineered soft piezoelectric architectures leverage chemically activated interfaces to amplify ultrasound-driven electromechanical coupling, enabling bioinspired, scalable communication with cells efficient.

Background/Objectives: Nature-inspired therapeutic strategies that promote biological regenerative mechanisms and replicate the native structural microenvironment conductive to formation of healthy tissue are increasingly recognized as a promising platform for skin tissue regeneration and wound healing. This study proposes an innovative design of novel multifunctional scaffolds composed entirely of natural components—gelatin, L-ascorbic (ASA) acid and allantoin—as a bioinspired approach for skin tissue regeneration through pro-regenerative, antimicrobial, and keratinocyte-supportive properties. Methods: The biocompatible, skin-adhesive scaffolds were prepared via a simple and environmentally friendly heat-induced crosslinking of gelatin with varying ASA contents, and by enriching the system with allantoin. The influence of ASA content on scaffold properties was investigated through characterization of their morphology, porosity, swelling behavior, skin tissue adhesion, and allantoin release potential. Biocompatibility was evaluated in vitro using human keratinocyte (HaCaT) cells, while antibacterial activity was assessed against Escherichia coli and Staphylococcus epidermidis. Results: The scaffolds revealed a highly porous, interconnected structure with tunable porosity (87.37–92.39%) and soft-tissue-matched mechanical properties (0.81–1.47 MPa). Incorporation of allantoin into the scaffolds enhanced their mechanical performance and swelling capacity. All scaffolds demonstrated antibacterial activity against both tested bacteria, supported keratinocyte viability and provided sustained release of allantoin for up to 76 h, confirming their multifunctional pro-regenerative potential. Conclusions: The novel gelatin/ascorbic acid scaffolds enriched with allantoin combine a porous replicated structure of native extracellular matrix, fluid absorption capacity, soft-tissue-like mechanical properties, stable skin tissue adhesion, cytocompatibility and antibacterial functionality with the pro-regenerative properties of allantoin, thereby representing a multifunctional and biologically inspired platform for advanced skin tissue regeneration and wound-healing applications.

A ZnO filler and cold atmospheric plasma boost the US response of piezo-PLLA films and improve cell–film contact. Enhanced piezostimulation transfers stimuli more efficiently, increasing antimicrobial activity and promoting human cell proliferation.

The main limitations of using a high-temperature drawing approach to tailor poly-l-lactide (PLLA) crystallization and molecular orientation for ultrasound-active piezoelectric structures stem from the intrinsic properties of the processed polymer, including low melting/softening elasticity and slow crystallization kinetics. Here, we found that applying different contacting layers, including polytetrafluoroethylene (PTFE) (as Teflon and Teflon S), cellulose (Paper) or polyimide (Kapton) deposited at the surface of PLLA, significantly affects the drawing process and tailors its oriented crystallization and molecular chain orientation. Consequently, the contacting layers contribute to the piezoelectric properties of PLLA (alone or with added morphologically anisotropic hydroxyapatite (HAp) filler), affecting its activation via ultrasound and generated electro-signal. Human keratinocytes (HaCaT cells) stimulated on these surfaces are shown to receive and respond to the transferred stimuli via the activation of the cytoskeleton and directional migration. The high-temperature (250 °C) drawing approach with contacting layers is a simple, solvent-free and economically viable way of broadening the applications of classical high-temperature drawing, opening new possibilities for further tailoring the piezoelectricity of organic piezoelectrics.

The main limitation of high-temperature drawing approach for tailoring crystallization and molecular orientation of poly-l-lactide (PLLA) toward ultrasound- active piezoelectric structures is set by intrinsic properties of the processed polymer, including low melting / softening elasticity and slow crystallization kinetics. Here we found that application of different contacting layers, including polytetrafluoroethylene (PTFE) (as Teflon and Teflon S), cellulose (paper) or polyimine (Kapton) deposited at the surface of PLLA, significantly affects the drawing process and tailors its oriented crystallization and molecular chain orientation. Consequently the contacting layers contribute to piezoelectric properties of PLLA, affect their activation by ultrasound and generated electro-signal. Human keratinocytes (HaCaT cells) grown stimulated on these surfaces are shown to receive and respond to the transferred stimuli by activation of the cytoskeleton and directional migration. The high-temperature drawing approach with contacting layers is simple, solvent-free and economically continent way for broadening limitations of classical high-temperature drawing which opens new possibilities for further tailoring piezoelectricity of organic piezoelectrics.

Objectives: To develop and evaluate graphene oxide/gelatin/alginate scaffolds for advanced wound therapy capable of mimicking the native extracellular matrix (ECM) and bio-stimulating all specific phases of the wound healing process, from inflammation and proliferation to the remodeling of damaged skin tissue in three dimensions. Methods: The scaffolds were engineered as interpenetrating polymeric networks by the crosslinking reaction of gelatin in the presence of alginate and characterized by structural, morphological, mechanical, swelling properties, porosity, adhesion to the skin tissue, wettability, and in vitro simultaneous release of the active agents. Biocompatibility of the scaffolds were evaluated in vitro by MTT test on fibroblasts (MRC5 cells) and in vivo using Caenorhabditis elegans assay. Results: The scaffolds exhibited a highly porous interconnected morphology with adjustable porosity (93–96%) and mechanical strength (1.10–2.90 MPa), hydrophilic nature with high capacity to absorb physiological fluids, and stable adhesion to the skin tissue. The obtained results of MRC5 cell viability indicate that the scaffolds are safe for biomedical applications. No mortality was detected among the Caenorhabditis elegans throughout the incubation period, indicating that the scaffolds are not toxic. The results of in vitro release study of allantoin, quercetin, and caffeic acid confirm the scaffolds’ significant potential for simultaneous release. Conclusion: The graphene oxide/gelatin/alginate scaffolds are promising candidates for non-invasive, dual ECM-mimetic, and multi-target wound therapy, offering an innovative strategy to address the complexities of wound healing process.