Report

Teaser, summary, work performed and final results

Periodic Reporting for period 3 - CELL HYBRIDGE (3D Scaffolds as a Stem Cell Delivery System for Musculoskeletal Regenerative Medicine)

Teaser

Aging worldwide population demands new solutions to permanently restore damaged tissues, thus reducing healthcare costs. Regenerative medicine offers alternative therapies for tissue repair. Although first clinical trials revealed excellent initial response after implantation...

Summary

Aging worldwide population demands new solutions to permanently restore damaged tissues, thus reducing healthcare costs. Regenerative medicine offers alternative therapies for tissue repair. Although first clinical trials revealed excellent initial response after implantation of these engineered tissues, long-term follow-ups demonstrated that degeneration and lack of integration with the surrounding tissues occur. Causes are related to insufficient cell-material interactions and loss of cell potency when cultured in two-dimensional substrates, among others.
Stem cells are a promising alternative due to their differentiation potential into multiple lineages. Yet, better control over cell-material interactions is necessary to maintain tissue engineered constructs in time. It is crucial to control stem cell quiescence, proliferation and differentiation in three-dimensional scaffolds while maintaining cells viable in situ. Stem cell activity is controlled by a complex cascade of signals called “niche”, where the extra-cellular matrix (ECM) surrounding the cells play a major role. Designing scaffolds inspired by this cellular niche and its ECM may lead to engineered tissues with instructive properties characterized by enhanced homeostasis, stability and integration with the surrounding milieu.
This research proposal aims at engineering constructs where scaffolds work as stem cell delivery systems actively controlling cell quiescence, proliferation, and differentiation. This challenge will be approached through a biomimetic design inspired by the mesenchymal stem cell niche. Three different scaffolds will be combined to achieve this purpose: (i) a scaffold designed to maintain cell quiescence; (ii) a scaffold designed to promote cell proliferation; and (iii) a scaffold designed to control cell differentiation. To prove the design criteria, the evaluation of stem cell quiescence, proliferation, and differentiation will be assessed for musculoskeletal regenerative therapies.

Work performed

We are making progress in all work packages (WP), namely WP1, WP2, WP3, WP4, and WP5. In WP1, we started to optimize the protocol to modify hydrogels with biological moieties that could be of interest to maintain cell quiescence. Furthermore, protocols to study cell quiescence are being developed. In WP2, we started to work on optimization of the surface properties of electrospun fibers, and most interestingly we have developed a method to increase cell migration capacity throughout the scaffolds. Equally interesting, we have found out that cells in 3D express much lower levels of lamins compared to conventional 2D cultures. This might lead to important fundamental discoveries. In WP3, we have started to develop protocols for brush binding to 3D printed scaffolds and are currently exploring the possibility to conduct proteomics studies to discover the protein signature on 3D scaffolds for osteochondral differentiation. In addition, looking at facilitating the clinical translation of the end results of the project, we are also currently evaluating the use of human platelet lysate instead of the classical fetal bovine serum. In WP4, we have started to study the integration of the different scaffolds compartments developed in WP1, WP2, and WP3. In particular, we have started to study the interface between the hydrogel and the electrospun compartments. In WP5, we have obtained the ethical permission to perform animal studies and are currently designing the first working protocols.

Final results

Progress beyond the state of the art and potential scientific and socio-economic impact are still as described in the original description of action of the project.

Website & more info

More info: http://www.moronilab.org.