Tuning Tissue Growth with Scaffold Degradation in Enzyme-Sensitive Hydrogels
How to tune tissue growth with hydrogel degradation?
Franck J. Vernerey
Dpt. of Mechanical Engineering, University of Colorado, Boulder
k: franck.vernerey@colorado.edu
http: // vernereygroup. wordpress. com
Abstract
Despite tremendous advances in the field of tissue engineering, a number of
obstacles are still hindering its successful translation to the clinic. One of these
challenges has been to design cell-laden scaffolds that can provide an appropriate environment for cells to successfully synthesize new tissue while providing
a mechanical support that can resist physiological loads at the early stage of
in-situ implementation. A solution to this problem has been to balance tissue
growth and scaffold degradation by creating new hydrogel systems that possess both hydrolytic and enzymatic degradation behaviors. Very little is known,
however, about the complex behavior of these systems, emphasizing the need
for a rigorous mathematical approach that can eventually assist and guide experimental advances. To address this issue, I will discuss a model for interstitial
growth based on mixture theory, that can capture the coupling between degradation, swelling, and transport of extracellular matrix (ECM) molecules released
by cartilage cells (chondrocytes) within a hydrogel scaffold. The model particularly investigates the relative roles of hydrolytic and enzymatic degradations
on ECM diffusion and their impacts on two important outcomes: the extent of
ECM transport (and deposition) and the evolution of the scaffold’s mechanical
integrity. Numerical results based on finite element analysis show that if
properly tuned, enzymatic
degradation differs from hydrolytic degradation in that
it can create a degradation
front that is key to maintaining scaffold stiffness while
allowing ECM deposition.
These results therefore suggest a hydrogel design that
could enable successful insitu cartilage tissue engineering
(a) The construct is composed of cells and the mixture of solid and fluid phases
which are either secreted by cell or key elements of porous scaffold. (b) Growth
in hydrogel scaffolds at microscale is shown. In this study we consider two cellsecreted molecules; enzymes and ECM, which are essential to model the tissue
growth and hydrogel degradation. (c) Cartilage cells secreted extracellular matrix, shown by histological images stained for aggrecan, which increased as a
function of time. By week 12, there was evidence of matrix connectivity in
the hydrogel. The compressive modulus of the construct decreased with culture
time indicating that the hydrogel was undergoing bulk degradation.
References
[1] V ERNEREY F. J., A mixture approach to investigate interstitial growth in
engineering scaffolds. Biomech. Model. Mechanobiol., 1-20, 2015.
[2] A KALP U., C HU S., S KAALURE S. C., B RYANT S. J., D OOSTAN A.,
V ERNEREY F. J. Determination of the Polymer-Solvent Interaction Parameter for PEG Hydrogels in Water: Application of a Self Learning Algorithm. Polymer, 66:1,135-147, 2015.
[3] D HOTE V., V ERNEREY F. J., Mathematical model of the role of degradation on matrix development in hydrogel scaffold. Biomech. Model.
Mechanobiol., 13:1, 167-183, 2014.
[4] D HOTE V., S KAALURE S., A KALP U., ROBERTS J., B RYANT S. J.,
V ERNEREY F. J., On the role of hydrogel structure and degradation in
controlling the transport of cell-secreted matrix molecules for engineered
cartilage. J. Mech. Behav. Biomed. Mater., 19:61-74, 2013.
Vita
Dr. Vernerey is an Associate Professor and
and head of the Programmable Active Soft
Matter Research Group in Mechanical Engineering at the University of Colorado, Boulder. He received his Ph.D. from Northwestern University in 2006 in the field of Theoretical and Applied Mechanics with a concentration on continuum mechanics and multiscale
methods.
His expertise lies in using theoretical and computational approaches to better
understand, control and tune the response of active soft matter, including active particles, vesicles and hydrogels. Applications range from bio-separation,
targeted drug delivery and tissue engineering. Dr. Vernerey is the recipient of
the 2014 NSF CAREER award, is currently the principal investigator of several projects funded by the US National Science Foundation and the National
Institute of Health and is the author of about 50 scientific publications.
Lectures series
The mission of the lecture series is to bring the most outstanding
scholars in the area of mechanical behaviour of materials to University of Reims and to expose our students, faculty, and professional
community to the latest advances in the field.
• Séminaires SFR CAP-Santé, Reims
Jeudi 28 janvier 2016 à 11h00,
Salle ”Biomolécules”,
RdC des UFRs de Pharmacie et de Médecine.
The future integrated multiscale analysis system will be
constructed based on complexity science-based mathematical framework. As regard bone and cartilage
tissue engineering, biopolymers have been extensively
used owing to their ability to favourably interact with
cells and also to be susceptible to enzymatic degradation providing space for tissue ingrowth. In this context, using porous polymeric gels as biomimetic materials, it is crucial to appreciate that several concomitant
approaches are always required.
Host: Prof. Sophie Gangloff
BIOS EA 4691, Université de Reims
For more information about this event contact the seminar coordinator Dr. Larbi Siad at
k larbi.siad@univ-reims.fr
03 26 91 89 77
H 06 33 20 90 11