Technology

The most basic units of life are cells. An adult is comprised of trillions of cells. Many diseases are related to cells, for example cancer cells with their uncontrolled cell growth. Stem cells are "unspecialized" cells in your body, which divide and become specialized cells such as liver cells, muscle cells, blood cells, or other cells. Therefore, stem cells are an exciting area in medicine because of their potential to regenerate and repair damaged tissue.

At the moment, several studies are ongoing in which design materials are used to induce stem cell differentiation within a 3D environment. However, it is very difficult to form three-dimensional artificial tissues similar to the structurally complex tissue within the human body due to the technical limits in biomaterials. Drawbacks of the current matrices are poor reproducibility due to changes in composition between batches, animal origin and harsh method to recover cells from the matrix.

Polyisocyanopeptide (PIC) hydrogel is a new class of advanced polymers. The complex chemistry of the polymer allows the organization into a helix-like structure that is similar to the conformation of collagen, abundantly present in the extracellular matrix (structure around cells). 

PIC hydrogel is an improved platform for cell studies, because it combines the unique benefits of natural and synthetic biomaterials. PIC hydrogels uniquely perform like collagen, while possessing the same characteristics as other commercial hydrogels. Furthermore, it is fully reversible thermo sensitive, cells can be easy recovered and downstream processing after culturing is straightforward.

The unique combination of tunable biofunctionality and biomechanics of the PIC hydrogels makes them excellent matrices for 3D stem cell culture or regenerative medicine.

In addition, PIC has a strain stiffness that increases under applied force, thereby enabling hydrogel strain stiffness modulation according to the needs of each cell type. Hereby, PIC hydrogels create a cellular microenvironment with the right mechanical cues to control cell expansion and differentiation.

 

Advantages of PIC hydrogel

No batch to batch variation - because of synthetic origin

Excellent cell growth and differentiation

Represents biomechanical properties similar to natural matrices - same elasticity as collagen

Easy to use - reversible thermosensitive:
•    no difficulties in cell or organoid isolation
•    no difficulties with downstream processing or imaging after culturing

Biofunctionality -  by clicking (growth) factor of choice to the polymer

Non-toxic


Noviocell will build upon its synthetic PIC hydrogels and develop them into easy-to-use solutions. 

Drawbacks Natural matrices

Batch to batch variation - their exact composition cannot be defined

Pathogen transmission and immunogenicity

Technical challenges in handling - difficulties in cell or organoid isolation

Technical challenges with downstream processing after culturing - imaging

Experimental inertness - inability to experimentally vary composition

Due to their composition, they cannot be used for regenerative medicine

Drawbacks other Synthetic matrices

Do not adequately represent the complicated extracellular matrix

Limited cell growth and differentiation

Technical challenges in handling - difficulties in cell or organoid isolation

Technical challenges with downstream processing after culturing - imaging

References


Kouwer PHJ, Koepf M, Le Sage VAA, Jaspers M, van Buul AM, Eksteen-Akeroyd ZH, et al. Responsive biomimetic networks from polyisocyanopeptide hydrogels. Nature 2013.

Jaspers M, Dennison M, Mabesoone MFJ, MacKintosh FC, Rowan AE, Kouwer PHJ. Ultra-responsive soft matter from strain-stiffening hydrogels. Nat Commun. 2014.

Das RK, Gocheva V, Hammink R, Zouani OF, Rowan AE. Stress-stiffening-mediated stem-cell commitment switch in soft responsive hydrogels. Nat Mater 2015.

Bruekers, SMC, Jaspers M, Hendriks JMA, Kurniawan NA, Koenderink GH, Kouwer PHJ, Rowan AE, Huck WTS. Fibrin/fiber architecture influences cell spreading and differentiation. Cell Adhesion & Migration 2016.

Jaspers M, Pape ACH, Voets IK, Rowan AE, Portale G, Kouwer PHJ. Bundle formation in biomimectic hydrogels. Biomacromolecules 2016.

Zinkevich T, Venderbosch B, Jaspers M, Kouwer PHJ, Rowan AE, van Eck ERH, Kentgens APM. Solid state NMR characterization of tri-ethyleneglycol grafted polyisocynopeptides. Magn. Reson. Chem. 2016.

Mihaila S, Rowan AE, Feitz, WF, Oosterwijk E. Matrix-stiffness Driven Osteogenic Differentiation of Human Adipose Derived Stem Cells, TERMIS 2015.

Sun W, Eksteen-Akeroyd ZH, Nagelkerke A, Geutjes P, Zhou L, Wissing T, Wilson C, Feitz WF, Rowan AE, Oosterwijk E. Novel Polyisocyanopeptide Hydrogels for Rapid Vasculogenesis. TERMIS 2015.