Promising treatment approaches in repairing tissue defects include implementation
of regenerative medicine strategies, particularly delivery of preadipocytes to sites
where adipose tissue damage needs to be repaired or where fat needs to be generated.
In this study, we suggest that the injectable hyaluronic acid/adipic acid dihydrazide
(HA/ADH) hydrogel may be an adipose-tissue-like material in terms of biological compatibility
as well as mechanical behavior. First, we show that the hydrogel enables and supports
growth, proliferation and differentiation of 3T3-L1 preadipocytes. Second, given that
adipose tissue is a weight-bearing biological structure, we investigate the large
deformation mechanical behavior of the hydrogel with and without embedded preadipocytes,
by performing confined and unconfined compression tests and then calibrating a strain
energy density (SED) function to the results. Four test groups were examined: (1)
Hydrogel specimens right after the preparation without cells, (2) and (3) 3-days-cultured
hydrogel specimens with and without cells, respectively, and (4) 6-days-cultured hydrogel
specimens with cells. A one-term Ogden SED was found to adequately describe the hyperelastic
behavior of the hydrogel specimens in all experimental groups. Importantly, we found
that the mechanical properties of the hydrogel, when subjected to compression, are
in good agreement with those of native adipose tissue, with the better fit occurring
3-6 days after preparation of the hydrogel. Third, computational finite element studies
of the mechanical (stress-strain) behavior of the HA/ADH hydrogel when containing
mature adipocytes indicated that the stiffnesses of the constructs were mildly affected
by the presence of the adipocytes. Hence, we conclude that injectable HA/ADH hydrogel
may serve as a vessel for protecting preadipocytes during, and at a short-term after
delivery to native tissues, e.g. in research towards regenerative medicine in tissue
reconstructions.