Nano-fibrous tissue engineering scaffolds capable of growth factor delivery

Abstract

Tissue engineering aims at constructing biological substitutes to repair damaged tissues. Three-dimensional (3D) porous scaffolds are commonly utilized to define the 3D geometry of tissue engineering constructs and provide adequate pore space and surface to support cell attachment, migration, proliferation, differentiation and neo tissue genesis. Biomimetic 3D scaffolds provide synthetic microenvironments that mimic the natural regeneration microenvironments and promote tissue regeneration process. While nano-fibrous (NF) scaffolds are constructed to mimic the architecture of NF extracellular matrix, controlled-release growth factors are incorporated to modulate the regeneration process. The present article summarizes current advances in methods to fabricate NF polymer scaffolds and the technologies to incorporate controlled growth factor delivery systems into 3D scaffolds, followed by examples of accelerated regeneration when the scaffolds with growth factor releasing capacity are applied in animal models.

Fig. 1

Scanning electron micrographs of a macro-porous NF PLLA scaffold prepared from sugar sphere template leaching and TIPS, with (A) macro-pore network structure and (B) NF wall matrix architecture (37). Reproduced with permission from John Wiley & Sons.

Fig. 2

Scanning electron micrographs of a PLGA NS immobilized PLLA NF scaffold: (A) macro-pore network structure of the NS-containing scaffold and (B) NS immobilized on the NF wall matrices (53). Reproduced with permission from Elsevier.

Fig. 3

In vitro release kinetics of BMP-7 from NS-immobilized scaffolds. Three distinct release profiles were achieved with NS composed of different LG/GA ratios (50/50 or 75/25) or molecular weights (6.5 K, 64 K or 113 K) (53). Reproduced with permission from Elsevier.

Fig. 4

BMP-7 NS-containing scaffolds induced ectopic bone formation after subcutaneously implanted in rats for six weeks: (A) fibrous tissue growth in the NS-containing scaffolds without BMP-7, (B) fibrous tissue growth in the NS-containing scaffolds adsorbed with 5 μg BMP-7/scaffold, and (C) bone formation in the NS-containing scaffolds encapsulated with 5 μg BMP-7/scaffold (H&E staining) (53). Reproduced with permission from Elsevier.

Fig. 5

MS-scaffolds encapsulating PDGF promoted angiogenesis in a release profile-dependant way, after subcutaneously implanted in rats for one week. Left panel is at a lower magnification (10×), right panel is at a higher magnification (40×). (A), (D) blank scaffolds, (B), (E) fast-releasing MS-scaffolds encapsulating 25 μg PDGF/scaffold, and (C), (F) slow-releasing MS-scaffolds encapsulating 25 μg PDGF/scaffold (von Willebrand factor immunohistochemical staining) (77).