Project Portugal 2030

Summary

In response to the multifaceted challenges associated with diabetic foot ulcers (DFUs), the SMART-HEAL aims to strategically address the DFU complex healing process using therapeutical tools based on naturally derived materials and plant-extracted bioactive components to enhance wound healing efficacy, mitigate infection risks, and foster a moist and favorable environment for recovery across the spectrum of DFU severities. The proposed approach also underlines our commitment to innovative solutions to reduce their environmental impact. The project outlines the key strategies: (A) Design and development of a multifunctional 3D family of natural-origin architectures with flexibility to adapt to diverse wound characteristics. The proposed 3D delivery devices will be pH-responsive microfluidic microspheres loaded with NCs embedded into oleogels to serve as a drug delivery depot at the clinical site. These devices based on natural resources will be scalable due to reproducible manufacturing technologies to prioritize environmentally friendly and cost-efficient medical device production systems. (B) Implement a flexible platform based on ionic liquid (IL) technologies to isolate plant bioactive components. Biocompatible ionic liquids (Bio-ILs) will be utilized to selectively enhance the solubility of target compounds, facilitating mild extraction conditions to preserve the integrity of natural compounds (NCs) and reducing their risk of degradation. Besides, the tailored Bio-ILs are often non-toxic and recyclable, and they will offer higher NC yields and increased purity. Bio-ILs will isolate NCs such as acemannan and curcumin derived from Aloe vera and Curcuma longa. These NCs possess anti-inflammatory and oxidant features, among other specificities, and their incorporation into the proposed systems will create innovative wound care solutions. (C) link the physicochemical performance of the proposed devices and their biological response to establish their applicability in wound healing. Quantified clinical requirements (permeability, degradation, targeted delivery concentrations, and release kinetics) and therapeutic action of the matrices will be assessed to guide the development of the final device. in vitro assessment of the impact of the devices on direct interactions with human cell lines, specifically fibroblasts and keratinocytes will be made. Also, the effects of in vivo stimulation and inhibition of active agents released from the matrices, particularly on angiogenesis, will be explored. Simultaneously, the study will conduct an in vivo assessment of the active agent's penetration using skin models. These initial assays would serve as a crucial screening step to select the formulations that exhibit promising results for further in vivo investigation. Full-thickness skin defects created on rats' backs will be employed to evaluate the healing effects of selected value-added matrices. In SMART-HEAL, outreach activities will be implemented to engage the general public, collaborators, and stakeholders. Dissemination actions of the project will involve open-access publications, conferences, and workshops. SMART-HEAL will be an opportunity to raise critical knowledge on material-based technologies, answering society, clinical, and market demand for effective drug delivery systems for DFU care. The fabricated medical devices can be adapted for other chronic wounds. The proposal approaches are aligned with the goals of the 2030 Agenda.