Synthesis and characterization of tunable PEG-based hydrogel : From injectable to 3D printable biomimetic constructs for tissue engineering applications

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Context

The development of multifunctional hydrogel platforms for tissue engineering, injectable cell therapies and in vitro 3D modeling has become one of the most active fronts in biomedical research. Most current systems face a fundamental trade-off: increasing mechanical performance to match with specific human tissues typically compromises cytocompatibility or injectability, and vice versa.
The clinical translation of tissue-engineered constructs is additionally constrained by the absence of formulations combining shear-thinning injectability for minimally invasive delivery with postinjection recovery of mechanical stiffness and structural integrity. Natural polymers such as alginate, gelatin, hyaluronic acid and chitosan offer excellent biocompatibility, but suffer from poor mechanical tunability and limited long-term stability in physiological conditions. Synthetic polymers such as poly(ethylene glycol) (PEG), polyacrylamide and polyvinyl alcohol afford precise control over mechanical properties, yet are often biologically inert. To address these limitations, we aim to develop a versatile hydrogel platform, easy to prepare and to process, presenting tunable and robust mechanical properties matching with human tissues. To avoid the addition of any biopolymer networks and overengineered polymer synthesis, the strategy will be to functionalize a PEG backbone with reactive chemical groups naturally present in tissues (i.e., amines, aldehydes, acrylamide functions). By fine-tunning the incorporation of these moieties and crosslinking pathways, we aim to achieve both robust mechanical performance and intrinsic cell-supportive properties, within an injectable shear-thinning hydrogel for tissue engineering and 3D bioprinting.

Aim of the project

The ultimate goal of this master thesis project is to generate a library of PEG-acrylamide-based hydrogel formulations covering the full spectrum of tissue stiffnesses encountered in the human body, from soft neural tissues (~0,1 kPa) to cartilage and bone-adjacent scaffolds (~50 kPa).
This internship focuses on the rational design, synthesis, and physicochemical characterization of a library of PEG-based hydrogels. The strategy draws on a panel of complementary PEG precursors already synthesized and available in the laboratory. The combination of precursor architecture (molar mass, arm number, functional group density) and crosslinking pathway will allow systematic tuning of the hydrogel network topology, gelation rate and final mechanical properties.

Work Organization

The candidate will join the Polymer Materials Engineering Laboratory (IMP, UMR CNRS 5223), based at Polytech Lyon 1 and will integrate a vibrant, international, and multidisciplinary team working at the interface of polymer science and plasma medicine for biomedical applications.
The candidate will be supported by a tutor; subsequently, she/he will work autonomously, as soon as she/he has acquired the ability to perform the experimental work. This includes the design, synthesis, preparation and the optimization of PEG-based polymers and hydrogel formulations from these functional precursors. The physicochemical properties of the developed formulations (e.g., by rheology, compression tests, swelling/dissolution tests, etc.) will be assessed by the candidate in a second step. If time permits, cytotoxicity and preliminary biocompatibility assays on relevant primary cells or cell lines will be performed followed by cell encapsulation feasibility on selected formulations. The candidate has to show excellent organization skills that will be translated in its ability to design experiments, maintain a clear and clean lab notebook, and interpret data critically. She/he will be integrated into weekly team meetings and lab scientific life.

Background requirements

  • Background in polymer chemistry (synthesis and characterization of polymers).
  • Knowledge in rheology (flow and oscillatory principles) constitutes a strong asset.
  • Scientific rigor, self-motivation and enthusiastic positive attitude are demanded.
  • Proficiency in English is requested.

People to contact

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Summary