AngioChip: a biodegradable scaffold
with built-in vasculature for organ-ona-chip engineering and direct surgical
anastomosis
Boyang Zhang (Department of Chemical Engineering, University of Toront, Toronto, Ontario,
Canada.)
Miles Montgomery (Department of Chemical Engineering, University of Toront, Toronto,
Ontario, Canada.)
M. Dean Chamberlain (Institute of Biomaterials and Biomedical Engineering, University of
Toronto, Toronto, Ontario, Canad)
Laura A. Wells (Institute of Biomaterials and Biomedical Engineering, University of Toronto,
Toronto, Ontario, Canad)
Aric Pahnke (Department of Chemical Engineering, University of Toront, Toronto, Ontario,
Canada.)
Stéphane Massé (The Toby Hull Cardiac Fibrillation Management Laboratory, Toronto General
Hospital, Toronto, Ontario)
Jihye Kim (Department of Chemistry, University of Toronto, Toronto, Ontario, Canada)
Lewis Reis (Institute of Biomaterials and Biomedical Engineering, University of Toronto,
Toronto, Ontario, Canad)
Momen Abdulah (Toronto General Research Institute, University Health Network, Toronto,
Ontario, Canada.)
Sara S. Nunes (Toronto General Research Institute, University Health Network, Toronto,
Ontario, Canada.)
Kumaraswamy Nanthakumar (The Toby Hull Cardiac Fibrillation Management Laboratory,
Toronto General Hospital, Toronto, Ontario)
Michael V. Sefton (Department of Chemical Engineering, University of Toront, Toronto, Ontario,
Canada)
Milica Radisic (Department of Chemical Engineering, University of Toront, Toronto, Ontario,
Canada)
Introduction The fields of regenerative medicine and
tissue engineering have presented exciting
possibilities to regenerate tissues and organs.
Significant progresses have been made in the area
of skin, and bone replacement. Newly developed
bioengineering tools have moved this field further
towards regenerating complex solid organ such as
liver, pancreas, and heart, etc1. To generate
complex organs, the next-generation bioscaffold/biomaterial must provide intricate internal
architecture, such as a built-in 3-D micro-vascular
system, matching the complexity of a human organ.
Modern fabrication techniques, such as 3-D printing,
have demonstrated tremendous progress in this
area. However, one key problem in 3-D printing is to
solidify material rapidly upon deposition, which
limits the choices of biomaterials. In addition, it is
difficult to manufacture internal cavities by
depositing materials above an empty cavity2, such
as creating hollow channel networks mimicking
native vasculatures, which are required to deliver
nutrient into a tissue construct. Leaching of
sacrificial material to form cavity is limited by
availability of biocompatible solvent and leaching
product, hence further limiting the choice of
biomaterials. As results, few biomaterials have been
printed at high resolution with complex
vasculatures that meets the requirement of
tissue/organ replacement.
Materials and Methods
Results
We have developed a 3-D micro-patterning
technique that overcame the two obstacles
mentioned above. With this technique, thin
biomaterial sheets were pre-patterned, presolidified and stamped on to each other layer-bylayer to form complex suspended structures in the
micro-scale. This technique avoids the need of
rapidly solidifying deposited material and can
create internal cavities easily without sacrificial
materials. Complex bio-scaffolds made of a
synthetic biodegradable elastomer
(Poly(octamethylene maleate (anhydride) citrate)
(POMaC) )3 and includes built-in 3-D branched
vascular networks perfusible through a single inlet
and a single outlet have been fabricated (Figure 1).
The scaffolds exhibit anisotropic properties
matching the mechanical properties of adult rat
myocardium. The degradation rates and
permeability of the vascular scaffolds have also
been characterized. Furthermore, the vascular
scaffolds were used to engineer a vascularized
cardiac tissue patch from both neonatal rat
cardiomyocytes and human embryonic stem cell
derived cardiomyocytes (Figure 2), potentially used
for replacing damaged heart muscle after a heart
attack. Feasibility of surgically connecting the
scaffold vascular network to in vivo vascular system
was demonstrated on the femoral artery of rat
hindlimb in the preliminary animal study (Figure 3).
Discussion and Conclusion
This 3-D micro-patterning approach could provide
next generation bio-scaffolds that are valuable in
biological research for creating complex cellular
interaction, in drug discovery for creating complex
tissue model, and in regenerative medicine for
tissue replacement.
Scanning electron microscopy image of the cross sectional view of a vascular scaffold with multilayer interconnected branched networks. Scale bar: 400um (i), 200um (ii).
Confocal fluorescent images of Cardiac tissue patch and built-in micro-vasculature. A(i,ii)
Sarcomeric-α-actinin (green), actin (red), scale bar: 10um. A(iv) Troponin T (red). B(I,ii,iii,iV) CD31
(red), Scale bar: (i)200um, (ii, iii)100um.
Images of implanted vascular scaffold with surgical vascular anastomosis to the femoral artery of
rat hindlimb. (ii) Image of cardiac patch with built-in branched network perfusible through a single
inlet and outlet.
References
1 Laurencin, C. T. & Khan, Y. Regenerative engineering. Science translational medicine 4,
160ed169, doi:10.1126/scitranslmed.3004467 (2012). 2 Derby, B. Printing and
Prototyping of Tissues and Scaffolds. Science 338, 921-926,
doi:10.1126/science.1226340 (2012). 3 Tran, R. T. et al. Synthesis and characterization
of a biodegradable elastomer featuring a dual crosslinking mechanism. Soft Matter 6
(2010).