Lead Beneficiary – MATERIALS RESEARCH CENTER (MRC)

Objectives

The general objective of this WP is the development of technology methods for the synthesis of different MXenes (Tibased, non-Tibased) and their deposition to electrospun polymer membrane and fabric tissue.

To reach this objective, the following intermediate tasks should be solved:

  1. MXenes synthesis using different concentration of hydrofluoric acid (HF) or mixture (LiF or NaF + HCl) and etching temperature.
  2. To obtain MXene nanolaminates with tailored size and surface properties.
  3. To produce the 3D electrospun membranes using various polymers (PCL, PLA, PLCL, PU, Chitosan, etc.) for various applications.
  4. To deposit MXenes to as-synthesised electrospun materials and fabrics.

Description

Secondment visits, structured in 5 tasks, will have a preparatory period before the visit and a reporting period after the visit. In total, 110 secondment months are allocated to complete the WP’s tasks. Task leaders (Lead participants) of each Task are marked in bold font. WP1 Leader is MRC team.

Besides joint research efforts, discussions and finalisation of reporting documents, preparations of publications and conference thesis, lectures and scientific seminars are foreseen within each task of this WP.

Task 1.1. Synthesis, functionalisation and characterisation of Ti-based and non-Ti-based Mxenes [MRC]

Total number of person months allocated to secondments = 3

Mxenes (Ti3C2, V2C, Ta4C3, etc.) with precise control of surface chemistry (-O- and OH-terminations) will be synthesised from: 1) sintered MAX material by MRC partner and/or 2) commercially available MAX phases through wet chemical etching using HF or mixture (LiF or NaF + HCl).

Task 1.2. Characterisation of Mxenes [MRC, AMU]

Total number of person months allocated to secondments = 8

Mxenes with different synthesis and delamination modes will be assessed by MRC and AMU. The Mxenes characterisation protocol will include structural characterisation (SEM, XRD, XPS, EDX, UV), electrochemical characterisation (using 5 mM [K3FeCN6] 3-/4-), Cyclic voltammetry, and Electrochemical impedance spectroscopy.

Mechanical characterisation of fabricated Mxenes will be performed, measuring young modules, hardness, and stiffness.

Critical load and morphology of the material will be examined applying scratch test on the surface of the sample. Structure characterisation is going to be performed using Profilometer Huvitz HRM300, as well as various microscopic techniques (including SEM and AFM).

Task 1.3. Elaboration of porous 3D electrospun membranes from different polymers or polymer blends [UL, RESPILON]

Total number of person months allocated to secondments = 21

PCL, PLA, PLCL, collagen-derived polymers, pullulan, cellulose-derivates, and chitosan polymers will be used to produce 3D electrospun membranes using conventional, multi-needles, and coaxial electrospinning.

Also, we will prepare nanofibers using needleless emulsion electrospinning.

RESPILON (2 x 12M) and BIOFABICS (1x12M) will perform total of 36 PM to UL for development of nanofiber scaffolds. SSU will perform secondment to RESPILON for needleless electrospinning of scaffolds.

The main target of this task is to provide reliable solution for different expected applications – tissue engineering, cardiac and nerve tissue regeneration, iPSCs investigation and for wearable electronics.

Task 1.4. Deposition of MXenes on 3D electrospun scaffolds [UL, MRC, RESPILON]

Total number of person months allocated to secondments = 56

Innovative protocols for precise uniform deposition of MXenes to electrospun scaffolds will be developed. Different pretreatment methods, e.g. alkali and acidic treatment, oxygen plasma treatment, will apply to ensure deposition of MXene within all entire volume of scaffold. To secure the conductivity and biocompatibility, different MXenes with several deposition methods will be used.

Call: SEP-210925766 – HORIZON-MSCA-2022-SE-01 ESCULAPE EU Grants: Application form (Part B1) (HE MSCA SE): V2.2 – 04.10.2022

Task 1.5. Deposition of MXenes to fabric materials [UL, EDI, MRC]

Total number of person months allocated to secondments = 22

Application of wearable electronics requires some additional parameters, such as uniform distribution and resistance to detergents and water. To achieve these requirements, novel technology of deep-layer deposition of MXene will be applied with an aim of uniform distribution of MXenes in material with different thickness (from 1 to 5 mm).

Deliverables

D1.1 Protocol on MXenes synthesis and their characterisation

D1.2 3D electrospun polymer production protocols with MXene deposition

D1.3 Materials and process engineering training

Lead Beneficiary – UNIWERSYTET IM. ADAMA MICKIEWICZA WPOZNANIU (AMU)

Objectives

The general objective of this WP is to characterise the materials to achieve the appropriate properties for relatively required applications.

In addition, biodegradation of 3D scaffolds will be evaluated in vivo.

To reach this objective, the following intermediate tasks will be solved:

  1. Evaluation of structural properties of developed materials by SEM and AFM.
  2. EDX and FT-IR characterisation of electrospun mats to assess chemical properties after surface modification.
  3. Determination of the chemical structure of the biomaterials within degradation process by spectroscopic (FT-IR) methods.

Description

Secondment visits, structured in 5 tasks will have a preparatory period before the visit and a reporting period after the visit. In total, 80 secondment months are allocated to complete the WP’s tasks. Task leaders (Lead participants) of each Task are marked in bold font.

This WP will provide full characterisation of novel materials using structural, chemical, physical, and biological approaches with selection of materials for the specific application.

Besides joint research efforts, discussions, and finalisation of reporting documents, preparations of publications and conference thesis, lectures and scientific seminars are foreseen within each task of this WP.

Task 2.1. Characterisation of MXene-based membrane structural properties [UEF, AMU, RESPILON]

Total number of person months allocated to secondments = 32

Within this Task, we will provide structural characterisation of the tested materials on the basis of SEM/FIB, TEM, ICP-MS, DLS, and optical spectroscopy methods.

Task 2.2. Assessment of of MXene-based membrane chemical properties [AMU, VU]

Total number of person months allocated to secondments = 20

We will evaluate the effects of MXenes on chemical properties of materials after surface modification using XRD, Raman, FTIR methods.

Task 2.3. Biodegradation ability [UEF]

Total number of person months allocated to secondments = 10

Degradation in simulated fluids will be assessed for modified 3D mats. The chemical structure of the biomaterials within the degradation will be studied. 

Task 2.4. Evaluation of conductivity [AMU, VU]

Total number of person months allocated to secondments = 17

Electrical characterisation (electroconductive) of electrospun mats will be measured by means of a special homemade experimental setup based on Keithley instruments. The four-probe method will be used.

Task 2.5. Biocompatibility and toxicity evaluation [SSU]

Total number of person months allocated to secondments = 1

Cell viability, proliferation and differentiation potential of prepared and modified 3D mats will be evaluated on Mesenchymal Stem Cells (MSC), Schwann cells (SCs) and Cardiomyoblasts cell lines (www.atcc.org).

Cell proliferation assays and fluorescent microscopy will be used to investigate cell proliferation and migration within the scaffolds. Based on complex physical, chemical and biological evaluation of novel materials, appropriate 3D mats will be selected for the WP3 – testing towards biomedical application.

Deliverable

D2.1 Structural, chemical and degradation parameters of 2D mats depending on deposition techniques

D2.2 Technical report on results of conductivity

D2.3 Technical report on results of cell response

Lead Beneficiary – SUMY STATE UNIVERSITY (SSU)

Objectives

The general objective of this WP is to assess the effectiveness of newly produced materials and their effectiveness in tissue regeneration as a platform for tissue equivalents technologies. To reach this objective the following intermediate tasks will be solved:

  1. To assess the application of conductive 3D scaffolds for tissue engineering approaches [SSU].
  2. To study of in vitro/in vivo effectiveness of 3D matrix loaded with MXenes for regenerative medicine (cardiac patches and nerve tissue regeneration) [SSU, UNICAMP].
  3. To provide an extensive research human iPSC-derived cells for modelling of 3D matrix loaded with MXenes model regenerative medicine [Inserm].
  4. To study the effectiveness of MXene-based wearable devices and wearable biosensors (WBSs) for biomedicine [EDI, VU].

Description

Secondment visits, structured in 5 tasks will have a preparatory period before the visit and a reporting period after the visit. In total, 124 secondment months are allocated to complete the WP’s tasks. Task leaders (Lead participants) of each Task are marked in bold font. 

This WP will provide development of exploitation strategies by investigation of novel materials for tissue regeneration purpose, iPSCs biology, and wearable electronics.

Besides joint research efforts, discussions, and finalisation of reporting documents, preparations of publications and conference thesis, lectures and scientific seminars are foreseen within each task of this WP.

Task 3.1 Development of organ-on-chip and bioreactor chambers [BIOFABICS]

Total number of person months allocated to secondments = 66

Development of 3D printed organ-on-chip and bioreactor chambers with optimised shape and properties for tissue engineering and 3D cell culture use of nanofbrous scaffolds with MXenes.

Task 3.2. Assessment of 3D matrix loaded with MXenes in spinal ventral root reimplantation and stabilisation [UNICAMP]

Total number of person months allocated to secondments = 8

Combination of surgical repair of lesioned roots by the application of a fibrin biopolymer associated with the application will be evaluated on electrospun membrane functionalised with MXenes.

Task 3.3. Investigation of in-vivo effectiveness of heart tissue patches for cardiac injuries repair [SSU]

Total number of person months allocated to secondments = 6

The chronic model with ischemia/reperfusion injury will be created to assess the functional effects of cardiac patch implantation. The dynamic integration of the patch with the beating heart will be assessed, including histological and immunohistochemical investigation of heart samples.

Task 3.4. Investigation of human iPSC-derived cells for modelling of 3D matrix loaded with MXenes model regenerative medicine [Inserm]

Total number of person months allocated to secondments = 38

The fibrotic content induced by the ECM will be quantified and visualised by western blot and second harmonic generation using multiphotonic microscopy. The model will inherit cardiomyopathy, associated with DMD and neuronal dysfunction in DMD, using patient-derived neurons and cardiomyocytes. The impact of the healthy and pathological ECM will be compared using determined pathological features in vitro. By considering the severity of the DMD disease, dystrophin deficiency and its consequences on the cardiomyocyte ECM relationship dysfunction, the choice of this disease turns out to be very pertinent to investigate for the first time. The ECM property changes on patient-specific healthy and DMD hiPSC-CMs organised in 2D and 3D.

Task 3.5. Assessment of various wearable devices and wearable biosensors (WBSs) for biomedicine [EDI]

Total number of person months allocated to secondments = 6

We will employ 3D matrix loaded with MXenes in the wearable devices and wearable biosensors (WBSs).

MXenes based materials will also be assessed for use in various wearable devices in roles such as electrodes, wires, deformation sensors, etc. The most promising usecase will be selected to implement in a proof-of-concept wearable system prototype.

Deliverables

D3.1 – Training on assessment of human iPSC-derived cells for modelling of 3D matrix loaded with MXenes model regenerative medicine
D3.2 – Report about the medical application of MXeme-loaded membranes
D3.3 – Report on technologies involving the 3D matrix loaded with MXenes in the wearable devices and wearable biosensors

Lead Beneficiary – University of Latvia (UL)

Objectives

Management objectives: to ensure efficient delivery of administrative, legal, and financial aspects of the projects.

Dissemination and exploitation objectives: to provide efficient dissemination activities to support the plan for exploitation of project results by stakeholders during and after the project. Communication activities will inform industry and public about the project's output. One of the core dissemination objective is to transfer the research-based knowledge to companies and organisations that may adopt the usage of conductive MXene-based membranes biomedical strategy. Particularly, the specific objectives are:

  1. To promote the project among the relevant stakeholders including the general public, scientific community, policy makers and medical market players.
  2. To ensure that all the data generate in the project is findable, accessible, interoperable, and reusable (FAIR).
  3. To disseminate the project results among the main stakeholders to maximise the benefits of the results obtained in the project for maximum societal benefit.
  4. To use the results for their commercial exploitation to find and make new concepts of conductive MXene-based membranes biomedical strategies available in the market.

Description

Task 4.1. Coordination and communication

The PM will manage internal communication and organise quarterly consortium meetings alternating between online and in person. The PM will facilitate ethical and legal approval (as required).

Lead: UL will be the EC point of contact and will establish communication procedures, organise and record all meetings; ALL partners will contribute to regular meeting and prompt communications.

Task 4.2. Progress monitoring and reporting

The PM will monitor timelines for each deliverable and suggest reprioritisation if required. They will organise reporting to the funders (M12 & M24). Efficient implementation of the reporting requirements as defined in the Grant Agreement.

Lead: UL will monitor and approval all documents prior to submission the EC and provide a part-time project manager who will administer and collate financial and technical reports and deliverables; ALL partners contribute to reports.

Task 4.3. Financial Management

The task is to ensure that all budget related actions are performed correctly and within the rules and regulations set out by the Commission and the CA.

Lead: UL will receive and distribute all grant payments; ALL partners' financial departments will provide timely financial reports.

Task 4.4. Risk Management

This task implies regular review and updates to the risk register, and development of mitigation plans as required. Lead: UL will monitor and update the risk register ensuring it is an agenda item at all meetings; ALL partners will contribute to ongoing risk assessment and mitigation strategies.

Task 4.5. Dissemination and communications

The consortium will promote the results of the ESCULAPE project, as described in Section 2.3.1. A single project brand (logo and PR materials) will be developed to strengthen its outreach and recognition.

A GDPR-compliant list of stakeholders will be maintained as a mailing list.

Lead: AMU and VU will develop and launch the website and social media, prepare dissemination materials, manage the publication policy. ALL partners will contribute to preparing materials for dissemination and communications.

Task 4.6. IPR and Data Management

Exploitation and DMP will be established and implemented in accordance with the requirements of the FAIR Open Access of Research Data. The plans and updates will be included in the Plan for Exploitation, Dissemination and Use.

Lead: AMU will develop and manage the implantation of the DMP and work with in-house IP experts on the IPR strategy ALL will work to ensure compliance with the DMP and support the development of an IPR portfolio. 

Task 4.7. Exploitation Strategy

Identification of early adopters and evolution of preliminary plans for exploitation in Section 2.

Lead: MRC will develop the exploitation plans; ALL partners will contribute to the exploitation strategy, compliance with the DMP, and support the development of an IPR portfolio.

Deliverables

D4.1 – Dissemination, Exploitation and Communication plan

D4.2 – Data Management Plan

D4.3 – Progress report 1 

D4.4 – Mid-term meeting