Fabrication of nano-fibrous poly(l-lactic acid) scaffold reinforced by surface modified chitosan micro-fiber
Introduction
The goal of tissue engineering is to regenerate defective or damaged tissues and organs. One of the key factors of tissue engineering is the use of porous scaffolds to mimic the extracellular matrix (ECM) for cellular attachment, proliferation, and differentiation [1]. Collagen is the main ECM component in nearly every tissue including bone, skin, ligament, and tendon. The fibrillar structure of collagen, with a diameter range of 50–500 nm is important for cell adhesion and proliferation [2], [3], [4], [5]. A nano-fibrous scaffold should therefore serve as better environment for cell function [6], [7], [8]. Recent research has also validated that cells can attach and organize better around the nano-scale materials than their micro-scale counterparts [9], [10]. However, nano-scale scaffolds are usually weaker than the microscale scaffolds, limiting their applications in tissue engineering [11], [12]. If micro- and nano-fibers are combined in the same construct, the nano-network would favor cell growth and the micro-fibers would provide the scaffold with better mechanical properties.
Biodegradable synthetic and natural polymers are currently widely used to fabricate tissue engineering scaffolds. Synthetic PLLA is a non-toxic, biocompatible, and biodegradable material widely used in tissue engineering [13], [14], [15]. Previous studies have shown that nano-fibrous PLLA scaffolds could be fabricated by thermal induced phase separation (TIPS) method and had potential applications in nerve and vascular tissue engineering [15], [16]. However, PLLA has several obvious disadvantages, such as acidic degradation byproducts and hydrophobicity [17]. On the other hand, chitosan is a unique cationic polysaccharide constituted of N-glucosamine and N-acetyl-glucosamine units with many enticing properties, including hydrophilicity, non-toxicity, non-antigenicity, and cell affinity [18], [19], [20], [21]. To combine the individual advantages of synthetic and natural polymers, Jiao et al. reported that coating chitosan on a micro-scale PLLA scaffold could improve its mechanical strength and cell compatibility [22]. Moreover, chitosan solution could be spun into chitosan micro-fibers which have excellent mechanical properties. Li et al. significantly reinforced the micro-scale fibrous PLLA scaffolds with chitosan micro-fibers, but the chitosan fibers in the composite scaffold were not chemically bonded with the PLLA matrix [23], therefore the PLLA/chitosan scaffold is likely to rapidly degrade in body fluid. If the chitosan fiber were chemically bonded to the PLLA, it would strengthen and promote stability of the composite scaffold.
A nano-fibrous PLLA/surface modified micro-scale chitosan fibers composite scaffold would reinforce the mechanical properties of the scaffold effectively and improve the biocompatibility due to the chitosan micro-fibers. In this study, we prepared a nano-fibrous PLLA scaffold by TIPS method that was reinforced by surface modified chitosan micro-fiber. The morphology, mechanical performance, in vitro degradation, protein adsorption, and cytocompatiblity of the composite scaffold were also investigated.
Section snippets
Materials
PLLA with an inherent viscosity of 1.6 dl/g (MW = 56,000) was purchased from Shandong medical appliance company, China. Chitosan micro-fibers (95% deacetylated, diameter ∼20 μm) were provided from Donghua University, China. Dicyclohexylcarbodimide (DCC) was purchased by Haida Chemicals Company, China.
Surface modification of chitosan fiber
DCC is a widely used condensation agent in peptide synthesis. In this experiment, the surface modification of chitosan micro-fiber involved coupling the COOH functional group of PLLA with the NH2
Surface modification of chitosan fiber
The FTIR spectra obtained from chitosan fiber (CTSF) and surface modified chitosan fiber (MCTSF) are shown in Fig. 2. The CTSF spectrum shows characteristic peaks of OH (at 3433 cm−1), NH2 (at 2926 cm−1 and 1572 cm−1), COC (at 1126 cm−1). After the CTSF was chemically linked with PLLA, besides the CTSF characteristic peaks, the MCTSF spectrum showed new bands of 3240 cm−1 which originated from NHCO, and 1759 cm−1, which originated from the functional group CO of PLLA. These results suggested that the
Conclusions
In summary, nano PLLA/MCTSF composite scaffolds were successfully fabricated by the TIPS method. The scaffold morphology had a nano-fibrous PLLA matrix and a micro-scale MCTSF enhancement skeleton. Through the surface modification of CTSF, the interfacial connection of MCTSF to PLLA was significantly improved. MCTSF could be homogenously dispersed in the scaffold, and enhanced the compressive modulus of nano scaffolds effectively at different concentrations. Introduction of the alkalescence
Acknowledgments
The authors acknowledge the financial support from National Science Foundation of China (Grant No. 51043001) and Department of Science & Technology of Shandong Province (Grant No. 2011YD21025).
References (38)
- et al.
Prog. Polym. Sci.
(2010) - et al.
Trends Biotechnol.
(2010) - et al.
Biomaterials
(2012) - et al.
Adv. Drug Deliv. Rev.
(2012) - et al.
Biomaterials
(2012) - et al.
Compos. Sci. Technol.
(2006) - et al.
J. Mech. Behav. Biomed. Mater.
(2008) - et al.
Med. Eng. Phys.
(2010) - et al.
J. Control Release
(2011) - et al.
Biomaterials
(2005)
Biomaterials
Biomaterials
Biomaterials
Prog. Polym. Sci.
Int. J. Biol. Macromol.
Mater. Sci. Eng. C
Biomaterials
Biomaterials
Polym. Degrad. Stab.
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