Electrospun Collagen Nanofibers and Their Applications in Skin Tissue Engineering

Abstract

Electrospinning is a simple and versatile technique to fabricate continuous fibers with diameter ranging from micrometers to a few nanometers. To date, the number of polymers that have been electrospun has exceeded 200. In recent years, electrospinning has become one of the most popular scaffold fabrication techniques to prepare nanofiber mesh for tissue engineering applications. Collagen, the most abundant extracellular matrix protein in the human body, has been electrospun to fabricate biomimetic scaffolds that imitate the architecture of native human tissues. As collagen nanofibers are mechanically weak in nature, it is commonly cross-linked or blended with synthetic polymers to improve the mechanical strength without compromising the biological activity. Electrospun collagen nanofiber mesh has high surface area to volume ratio, tunable diameter and porosity, and excellent biological activity to regulate cell function and tissue formation. Due to these advantages, collagen nanofibers have been tested for the regeneration of a myriad of tissues and organs. In this review, we gave an overview of electrospinning, encompassing the history, the instrument settings, the spinning process and the parameters that affect fiber formation, with emphasis given to collagen nanofibers' fabrication and application, especially the use of collagen nanofibers in skin tissue engineering.

Keywords: Collagen; Electrospinning; Nanofiber; Scaffold; Skin; Tissue engineering.

Fig. 1

Classic concept of tissue engineering. Generally tissue engineering strategy involves the isolation of stem cells from a piece of healthy tissue. Harvested stem cells were cultured and expanded in vitro until the desirable cell number was achieved. Subsequently, the stem cells were seeded in 3-D constructs to form an engineered tissue which will be transplanted back to the patient. However, have to bear in mind that there are a number of different tissue engineering approaches which may skip or add additional steps to achieve the goal of tissue regeneration. For examples, the expanded stem cells can be injected directly back to the patient without a scaffold

Fig. 2

Schematic diagram of a typical electrospinning system. A Taylor cone is formed when polymeric solution collected at tip of needle is subjected to high electric potential. The polymeric solution whips across the gap between tip of capillary and grounded collector once electrical potential reached the critical value. Solvent is evaporated during traveling resulted in formation of solid non-woven fibers at grounded collector

Fig. 3

Schematic diagram of a coaxial electrospinning system A. Two different polymeric solutions were extruded through the inner needle and outer needle of a coaxial spinneret. The spinneret was subjected to high electrical potential for the formation of a charged jet that will whip across the distance towards the collector to form the coaxial nanofibers. Hollow nanofibers were produced when the core was removed. B and C Transmission electron microscopy image of coaxial nanofibers [170] (Reproduced with permission from MDPI). D Scanning electron microscopy image of hollow nanofibers (Reprinted with permission from Ref. [171]. Copyright ^© 2004 American Chemical Society)

Fig. 4

Schematic diagram of a bi-biofunctionalized coaxial nanofiber. Two different biomolecules were incorporated to the core and shell comprised of different polymers respectively. The shell will degrade first to release molecule A (round) followed by the degradation of the core to release molecule B (triangle) to achieve dual-stage molecule release

Fig. 5

Schematic diagram illustrating the mechanisms of pore formation on surface of nanofibers during the electrospinning process [172] (Reproduced with permission from Elsevier). Scanning electron microscopy image of porous nanofibers [173] (Reproduced with permission from Elsevier)

Fig. 6

Schematic diagram illustrating mixing and multilayering electrospinning system to produce mixed and multilayered nanofiber scaffolds

Fig. 7

Schematic diagram of commonly used cross-linking methods for collagen [174] (Reproduced with permission from BioMed Central)

Fig. 8

Schematic diagram showing in situ and post-electrospinning biofunctionalization of electrospun nanofibers

Fig. 9

Encapsulation of living cells within the electrospun nanofibers (Reprinted with permission from Ref. [121]. Copyright^© 2006 American Chemical Society)