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Review
. 2009 Mar-Apr;1(2):226-36.
doi: 10.1002/wnan.26.

Nanostructured polymer scaffolds for tissue engineering and regenerative medicine

I O Smith  1 , X H Liu, L A Smith, P X Ma
Affiliations
Review

Nanostructured polymer scaffolds for tissue engineering and regenerative medicine

I O Smith et al. Wiley Interdiscip Rev Nanomed Nanobiotechnol. 2009 Mar-Apr.

Abstract

The structural features of tissue engineering scaffolds affect cell response and must be engineered to support cell adhesion, proliferation and differentiation. The scaffold acts as an interim synthetic extracellular matrix (ECM) that cells interact with prior to forming a new tissue. In this review, bone tissue engineering is used as the primary example for the sake of brevity. We focus on nanofibrous scaffolds and the incorporation of other components including other nanofeatures into the scaffold structure. Since the ECM is comprised in large part of collagen fibers, between 50 and 500 nm in diameter, well-designed nanofibrous scaffolds mimic this structure. Our group has developed a novel thermally induced phase separation (TIPS) process in which a solution of biodegradable polymer is cast into a porous scaffold, resulting in a nanofibrous pore-wall structure. These nanoscale fibers have a diameter (50-500 nm) comparable to those collagen fibers found in the ECM. This process can then be combined with a porogen leaching technique, also developed by our group, to engineer an interconnected pore structure that promotes cell migration and tissue ingrowth in three dimensions. To improve upon efforts to incorporate a ceramic component into polymer scaffolds by mixing, our group has also developed a technique where apatite crystals are grown onto biodegradable polymer scaffolds by soaking them in simulated body fluid (SBF). By changing the polymer used, the concentration of ions in the SBF and by varying the treatment time, the size and distribution of these crystals are varied. Work is currently being done to improve the distribution of these crystals throughout three-dimensional scaffolds and to create nanoscale apatite deposits that better mimic those found in the ECM. In both nanofibrous and composite scaffolds, cell adhesion, proliferation and differentiation improved when compared to control scaffolds. Additionally, composite scaffolds showed a decrease in incidence of apoptosis when compared to polymer control in bone tissue engineering. Nanoparticles have been integrated into the nanostructured scaffolds to deliver biologically active molecules such as growth and differentiation factors to regulate cell behavior for optimal tissue regeneration.

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Figures

Figure 1
Figure 1
SEM micrographs of a PLLA fibrous matrix prepared from 2.5% (wt/v) PLLA/THF solution at a gelation temperature of 8°C: (a) ×50; (b) ×20K. (From Ma and Zhang [6], copyright 1999 by John Wiley & Sons, Inc. Reprinted with permission.)
Figure 2
Figure 2
SEM images of NF-PLLA scaffolds. (a) x100, (b) x2000. (From Liu et.al [38], copyright 2005 by American Scientific Publishers. Reprinted with permission.)
Figure 3
Figure 3
SEM micrographs of PLLA nano-fibrous scaffolds with incorporated PLGA50–64K nanospheres. (From Wei and Ma [41], copyright 2007 by Elsevier. Reprinted with permission.)
Figure 4
Figure 4
SEM micrographs of nano-HA/PLLA 50:50 scaffold, x100, x1000. (From Wei and Ma [50], copyright 2004 by Elsevier. Reprinted with permission.)
Figure 5
Figure 5
SEM micrographs of PDLAA scaffolds incubated in 1.5x SBF for 30 days. (From Zhang and Ma [52], copyright 2004 by John Wiley & Sons, Inc. Reprinted with permission.)
Figure 6
Figure 6
Scanning electron microscopic views of neonatal mouse osteoblasts cultured for 3 days: (A) on the solid-walled scaffolds and (B–D) on the nano-fibrous scaffolds. Original magnification; A and B 1000X, C and D 8000X. (From Woo et al. [68], copyright 2004 by Elsevier. Reprinted with permission.)
Figure 7
Figure 7
In vitro response of NF and SW PLLA scaffolds after seeding with MC3T3-E1 osteoblasts and cultured under differentiation conditions for 6 weeks. Shown are histological sections of representative areas within the scaffold. H&E staining showing (a) overview of a NF scaffold, (b) overview of a SW scaffold, (c) center region of a NF scaffold, and (d) center region of a SW scaffold. Von Kossa’s silver nitrate staining showing (e) center region of a NF scaffold, and (f) center region of a SW scaffold. Scale bars of (a), (b), (e), and (f); 500 μm. Scale bars of (c) and (d); 100 μm. * denotes the PLLA scaffold, # a scaffold pore. Arrows in von Kossa stained sections denote mineralization. NF scaffolds retained a small amount of the histological dyes and therefore are more visible than the SW scaffolds in the pictures. (From Chen et al. [28], copyright 1999 by Wiley & Sons, Inc. Reprinted with permission.)
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