MATRICES FOR ZONAL CARTILAGE TISSUE ENGINEERING - Intelligent Scaffolds for Tissue Engineering and Regenerative Medicine - page 749

engineering. Many other hydrogel materials also have potential
for cartilage tissue engineering, including chitosan, 93 hyaluronic
acid, 94 peptide-amphiphiles, 95 poly( N -isopropylacrylamide), and
poly(acrylic acid). 96 At this point, it is unclear whether an “ideal”
matrix will be found; there may, however, be specific material char-
acteristics that are “better” for specific regions of the cartilage and
foreachcelltype.Combinationofmultiplehydrogels,suchasfibrin-
alginate 97 or gelatin-chitosan, 98 may be useful to tailor properties
such as degradation and produce a protein-carbohydrate network
that resembles the collagen-glycosaminoglycan network of native
articular cartilage to a greater extent than single component hydro-
gels. Control over the organization of the matrix to replicate the
organizationoftheextracellularmatrixinarticularcartilage,suchas
the orientation of the collagen fibers, remains to be addressed. Bio-
mechanicalstimulationthroughspecificallydesignedbioreactors,or
in vivo stimulation, will likely be needed to achieve such organiza-
tion.
Work remains to be done to characterize cell responses to
thedifferenthydrogelsandintheformationofconstructswithzonal
differences. Studies to date have focused primarily on multiple lay-
eringtechniquestoeitherformthesecondlayeratopaprepolymer-
ized layer or combine two prepolymerized gels using an intermedi-
atelayerasanadhesive.Forthelatterapproach,natural“glues”such
as fibrin or novel chondroitin sulfate-based adhesives 99 have great
potential to forma strong interlayer bond.
More sophisticated approaches currently being investigated for
producing zonal constructs include hydrogel printing 100 using tech-
niques adapted from technologies used to produce polymer scaf-
folds for biomedical applications. 101 Incorporation of releasable
growth factor gradients, by embedding microcarriers in a hydro-
gel, is another approach recently taken to generating constructs
with zonal differences. 102 If typical zonal differences are attainable
andmaintainable in vitro ,zonaltissue-engineeredcartilagecouldbe
useful as an advanced model of cartilage behavior under various
stimulatory and disease conditions. Finally, the effectiveness of pre-
scribing zonal differences in vitro after implantation in vivo will be
key to determining whether or not such zonal matrices will be ben-
eficial in a clinicalsetting.