MICRO-AND NANOTECHNOLOGIES TO ENGINEER BONE REGENERATION - Micro and Nanotechnologies in Engineering Stem Cells and Tissues - page 231

which degrade the silk over a period of time. The addition of cell-binding domains
allows native tissue growth in the matrix, allowing tissue to attain normal physio-
logical function. 53 Addition of the peptide arginine-glycine-aspartic acid (RGD) to
the surface of silk films increases cell density. In a study, films with RGD peptide
on the surface had higher cell counts after 24 h, and cells continued to increase after
14 days (Fig. 10.5). 14
In vitro studies on electrospun silk scaffolds reported cell growth and ECM
formation after 14 days of incubation. Various combinations of silk, polyethylene
oxide (PEO), bone morphogenic protein 2 (BMP-2), and nHAp, were used to
fabricate scaffolds. BMP-2 and nHAp integrated scaffolds exhibited significant
increase in calcium deposition and BMP-2 transcription levels. 35 Enhanced attach-
ment and spreading of humanMSCs and anterior cruciate ligament (ACL) fibroblasts
was observed on RGD-modified silk scaffolds. 14 RGD functionalization also
increases cellular mineralization; osteoblast-like cells (Saos-2) mineralized signifi-
cantly on substrates containing parathyroid hormone. 55
10.5 SUMMARY
The research to date suggests that nano- and microparticles or fibers have immense
potential for applications in bone tissue engineering. Nanoparticles and nanofibers
have shown to improve the mechanical properties of biodegradable polymeric
implants. A few studies show that nano- and microparticle incorporated composite
and scaffold implants are cytocompatible (in vitro) and biocompatible (in vivo).
Some of the nanoparticles such as carbon nanotubes can also be functionalized for
targeting, drug delivery, and bioimaging. Furthermore, their intrinsic physical
properties can be harnessed for therapeutic and imaging applications. Although
these nano- and microparticles improve the mechanical properties of bone tissue
engineering scaffolds, little is known about their long-term biocompatibility and
biodistribution upon their release from the scaffolds in vivo. 61,62 Although silk
scaffolds produced by electrospinning are biocompatible, their mechanical propert-
ies can be improved by the dispersion of micro- and nanoparticles as reinforcing
agents. Furthermore cell-binding domains can be modified to limit their suscepti-
bility toward macrophage degradation. The future direction of tissue engineering
field will see attempts to overcome these challenges and continue to create more
biomimetic scaffolds because these nano- and microtechnologies show great promise
with multifunctional capabilities for bone tissue engineering.
ACKNOWLEDGMENTS
The authors would like to acknowledge of the financial support of the National
Institutes of Health (grants no. 1DP2OD007394-01).