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WIREs Nanomed Nanobiotechnol
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Nanostructured polymer scaffolds for tissue engineering and regenerative medicine

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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 Copyright © 2009 John Wiley & Sons, Inc. This article is categorized under: Implantable Materials and Surgical Technologies > Nanomaterials and Implants

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Scanning electron microscope micrographs of a poly(l‐lactic acid) (PLLA) fibrous matrix prepared from 2.5% (wt/v) PLLA/ tetrahydrofuran solution at a gelation temperature of 8°C: (a) × 50; (b) × 20 K. (Reprinted, with permission, from Ref. 6. Copyright 1999 Wiley Periodicals, Inc.).

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In vitro response of nanofibrous (NF) and solid‐walled (SW) poly(l‐lactic acid) (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 an NF scaffold, (b) overview of an SW scaffold, (c) center region of an NF scaffold, and (d) center region of an SW scaffold. Von Kossa's silver nitrate staining showing (e) center region of an NF scaffold, and (f) center region of an 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. (Reprinted, with permission, from Ref. 28. Copyright 2006 Elsevier).

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Scanning electron microscopic views of neonatal mouse osteoblasts cultured for 3 days: (a) on the solid‐walled (SW) scaffolds and (b, c) on the nanofibrous scaffolds. Original magnification; A and B 1000×, C 8000×. (Reprinted, with permission, from Ref. 68. Copyright 2004 Elsevier).

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SEM micrographs of PDLLA scaffolds incubated in 1.5× SBF for 30 days. (Reprinted, with permission, from Ref. 52. Copyright 2004 Wiley Periodicals, Inc.).

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SEM micrographs of nanoHA/PLLA 50 : 50 scaffold, × 100, × 1000. (Reprinted, with permission, from Ref. 50. Copyright 2004 Elsevier).

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SEM micrographs of poly(l‐lactic acid) (PLLA) nanofibrous scaffolds with incorporated PLGA50‐64K nanospheres. (Reprinted, with permission, from Ref. 41. Copyright 2007 Elsevier).

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SEM images of nanofibrous PLLA (NF‐PLLA) scaffolds. (a) × 100, (b) × 2000. (Reprinted, with permission, from Ref. 32. Copyright 2005 American Scientific Publishers.).

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