Noviocell BV proposes a novel ground breaking technology that will radically improve stem cell research, revolutionize the field of 3D cell culture, will enable personalized drug screening and reform the current therapeutic options for regenerative medicine.

Noviogel (PIC) is a fully synthetic biomimetic extracellular matrix; however, it has almost identical biomechanical properties to natural matrices. 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 ECM. In addition, the porous fibrous polymer network has a stiffness that increases under applied force similar to collagen or fibrin.

Technology Noviogel

Technology Noviogel 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.

Poly iso cyano peptide (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 bio-functionality 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.

L.M. Nibourg et al., Acta Ophthalmol.. 2016, 94, 721-729

L.M. Nibourg et al., Exp. Eye. Res. 2016, 143, 60-67

L. Ikonen et al., Biomed Research International. 2013, Article ID 285678

I. Kusters et al., PLoS ONE 2011, 6(5): e20435

A. Brizard et al., Angewandte Chemie, International Edition 2008, 47, 2063 – 20

F. Li et al. ChemPhysChem 2010, 11, 1956-196

M.R. de Jong et al., J. Control. Release, 132: e26-e27 (2008)

M. Montalti et al., Langmuir, 2006, 22, 2299 – 2303

K. J. C. van Bommel et al., Organic and Biomolecular Chemistry, 2005, 3, 2917 – 2920

M. De Loos et al., Org. Biomol. Chem. 2005, 3, 1631-1639

K.J.C. van Bommel et al. J. Control. Release 2005, 101, 287-290

A. Friggeri et al., Chemistry, a European Journal, 2005, 11, 5353 – 5361

A. Friggeri et al., Cosmetics & Toiletries 2005, 120: 67 – 76

K. J. C. van Bommel et al., Angewandte Chemie, International Edition 2004, 43, 1663 – 1667

A. Friggeri et al. J. Control. Release 2004, 97, 241-248

A. Heeres et al., Journal of the American Chemical Society, 2003, 125, 14252 – 14253

Jaspers M et al. Nonlinear mechanics of hybrid polymer networks that mimic the complex mechanical environment of cells. Nat Commun. 2017 May 25;8:15478.

Deshpande SR et al.Biomimetic Stress Sensitive Hydrogel Controlled by DNA Nanoswitches. Biomacromolecules. 2017 Oct 9;18(10):3310-3317.

Hammink R et al.Affinity-Based Purification of Polyisocyanopeptide Bioconjugates. Bioconjug Chem. 2017 Sep 15

Zimoch, J., et.al. Polyisocyanopeptide hydrogels: a novel thermo-responsive hydrogel re-vascularization and the development of organotypic structures, Acta Biomaterialia (2018)

Nehar Celikkin et al. 3D Printing of Thermoresponsive Polyisocyanide (PIC) Hydrogels as Bioink and Fugitive Material for Tissue Engineering Polymers 2018, 10, 555

Unique reversible thermo-sensitive characteristics

Synthetic origin and no batch-to-batch variation

Bio-degradable and non-toxic

Elastic behavior as collagen

Bio-functional applications through custom-made specific hydrogels

Get in touch?

If you require any further information or details, feel free to contact us.