Design of injectable hybrid platforms to tackle bacteria contamination and biofilm in chronic skin wounds
External reference persons Prof. Ana Leite Oliveira Universidade Catolica Portuguesa - Porto (Portogallo)
Research Groups 05-Bioingegneria Industriale
Thesis type EXPERIMENTAL, IN LAB
Description Chronic skin wounds represent one of the leading concerns faced by the healthcare systems daily, as millions of patients suffer from this pathology worldwide. Their treatment is a huge economical burden requiring expensive medical cares, long hospitalization and often leading to unsuccessful tissue healing. The major cause of delayed or failed wound closure is the spreading of high level of bacteria in the wound site, which promote the biofilm formation and interfere with the common pathway of matrix metalloproteinases responsible for tissue regeneration. To promptly tackle infections and disrupt the biofilm, patients are generally treated with high dosages of antibiotics for long periods thus, further promoting the development of antibiotic-resistant bacteria. For these reasons, researchers are hardly working on alternative antibiotic-free strategies to topically manage hard-to-close infected wounds. Among them, the design of hydrogel-based formulations releasing therapeutic ions (e.g., silver, iron oxide, zinc oxide) or naturally-derived molecules (e.g., tannic acid, gallic acid, curcumin, lactoferrin) has gained increasing interest. However, the uncontrolled payload release upon treatment administration remains a challenging issue. Hence, great effort has been devoted towards the investigation of strategies to personalize and tune the release of the encapsulated therapeutic agents, thus further increasing the effectiveness of such engineered formulations.
In this scenario, this Masterís thesis aims at developing an innovative injectable hybrid platform derived from the combination of ad hoc designed multi-stimuli responsive hydrogels and nanoparticles and able to face bacteria contamination through a smart and co-current release of multiple therapeutic agents. Specifically, an amphiphilic poly(ether-urethane) will be first synthesized and functionalized, promoting the exploitation of green approaches (e.g., plasma treatment), to prepare smart hydrogels responsive to temperature and alkaline pH and able to work as drug delivery carriers. Then, antimicrobial therapeutic agent-loaded nanocarriers will be developed and embedded in the hydrogel formulation to obtain hybrid platforms. Subsequently, such formulations will be in vitro characterized to assess their suitability as smart chronic wound treatments. Specifically, the hybrid hydrogels will be tested for their capability to: (i) co-currently entrap drug/nanocarriers within their network without affecting their responsiveness to temperature; (ii) release their payload via an alkaline pH-controlled mechanism and (iii) disrupt the biofilm through the dual-release of antibacterial agents, while preserving cell viability.
This work results from a collaboration between the Politecnico di Torino (Prof. Gianluca Ciardelli) and the Universidade Catolica Portoguesa (Prof. Ana Leite Oliveira).
The candidate will be supervised during the entire period of the thesis. He/she should be available to work both in Italy (Alessandria, 2-3 months) and in Portugal (Porto, 6 months). Specifically, the poly(ether urethane) synthesis, functionalization, physico-chemical characterization and hydrogel formulation will be performed at the Biomedical Lab in Alessandria; the nanocarrier engineering, their loading in the gelling formulation and the hybrid platform biological characterization will be performed at Prof. Oliveiraís Lab in Porto.
Required skills Max 2 exams left. Capacity for team working. Basic knolwedge in (bio)materials and nanotechnology preferred.
Deadline 26/10/2022 PROPONI LA TUA CANDIDATURA