Scaffolding plays a pivotal role in tissue engineering. To mimic the archit
ecture of a natural extracellular matrix component-collagen, nona-fibrous m
atrices have been created with synthetic biodegradable polymers in our labo
ratory using a phase-separation technique. To improve the cell seeding, dis
tribution, mass transport, and new tissue organization, three-dimensional m
acroporous architectures are built in the nano-fibrous matrices. Water-solu
ble poragen materials are first fabricated into three-dimensional negative
replicas of the desired macroporous architectures. Polymer solutions are th
en cast over the porogen assemblies in a mold, and are thermally phase-sepa
rated to form nano-fibrous matrices. The porogen materials are leached out
with water to finally form the synthetic nano-fibrous extracellular matrice
s with predesigned macroporous architectures. In this way, synthetic polyme
r matrices are created with architectural features at several levels, inclu
ding the anatomical shape of the matrix, macroporous elements (100 mu m to
millimeters), interfiber distance (microns), and the diameter of the fibers
(50-500 nm). These scaffolding materials circumvent the concerns of pathog
en transmission and immuno-rejection associated with natural collagen. With
the flexibility in the design of chemical structure, molecular weight, arc
hitecture, degradation rate, and mechanical properties, these novel synthet
ic matrices may serve as superior scaffolding for tissue engineering. (C) 2
000 John Wiley & Sons, Inc.