Development and Application of Naturally Renewable Scaffold Materials for Bone Tissue Engineering - The Nanoscience and Technology of Renewable Biomaterials - page 301

The hydrophilicity of cellulose is amongst the highest of any natural biomaterial.
Its ability to bond hydrogen is what allows nanofibrils to eventually form macroscopic
fibers and also retain significant amounts of water relative to the native mass of the
cellulose (5-10 times more water). In our tissue engineering work, we have hypothe-
sized, for example, that the overall hydrophilicity of a modified carboxy methylcellulose
(CMC) can be too high for normal cellular adhesion. We found that ASCs refrained
from symmetrically occupying the interstitial pore spaces of a CMC sample that had a
high carboxylation loading level. Although the cells appeared to be viable, a unique
cluster formation was observed that was anchored from a small number of attached cells
(unpublished data).
Another powerful feature of cellulose that abets successful tissue engineering is its
porosity and ability to allow cells to penetrate. For example, permanently implanted
MC can be penetrated by skin cells that are then able to migrate deep into the cellulose
net (106). This is a remarkable finding for the treatment of very deep burns because
the fibroblasts and keratinocytes can penetrate the porous net of cellulose, synthesize an
extracellular matrix, and form dermal tissue over time.
The aspect of bioabsorbability merits attention. In the last example, the tissue engi-
neering of skin is a very likely event, but in the final analysis MC will not degrade in the
short term. Of course, the time dependence of degradation/absorption is clearly impor-
tant: a biomaterial cannot be too labile or else it will fail to perform its primary function
of behaving as a perfusible medium to allow cellular adhesion, proliferation, and tissue
organization. Yet, if it is not absorbed, it may eventually inhibit or severely attenuate
the final desired prospect of tissue in-growth. Interestingly, cellulose does eventually
become methodically resorbed within a time frame that is compatible with most tissue
engineering programs (90 days), but its retention for longer periods of time (in fact, for
the entire life of the host) has not been known to cause any adverse inflammatory or
allergic reactions.
In general, cellulose is becoming a very versatile biomaterial for tissue engineering.
Cellulose can be used in a variety of applications in which it is often superior to its
synthetic counterparts due to its durability and biocompatibility.

11.3.4 Naturally Occurring Fibrous Protein Materials in BTE

Collagen, the most abundant protein in the body, has been extensively investigated for
biomedical applications. Collagen is a biocompatible, biodegradable, osteoinductive
material (6, 107). In addition, it has properties, such as amino acid sequences, that make
it an ideal material for cell attachment, proliferation, and differentiation (108). Kakudo
et al . was successful in using a three-dimensional (3D) human adipose-derived stem
cell (hASC) seeded collagen scaffold for a bone construct (109). After being cultured
in vitro for 14 days, the scaffolds were able to induce cell ingrowth and osteogenic
differentiation with the addition of osteogenic supplements in the culture media. Once
grown in vitro , the scaffolds were implanted into nude mice and new bone formation
occurred. In another application, Shih et al . showed that osteogenic differentiation of
bone marrow-derived hMSCs was significantly higher for cells grown on type I col-
lagen nanofibers compared to those seeded on polystyrene tissue culture plates (110).