Structurally optimized suture resistant polylactic acid (PLA)/poly (є-caprolactone) (PCL) blend based engineered nanofibrous mats

Highlight

• Response surface methodology and Taguchi experimental design enabled structural optimization of electrospun nanofibrous mats.

• Optimization of fiber diameter (~0.17 μm) and bead number (~0.3 × 10⁻³/μm²) for polylactic acid /poly (є-caprolactone) mats.

• Network cooperativity effects enhancing the suture retention strength and structural stability of optimized ENMs.

Abstract

The structural fabrication and optimization of polylactic acid (PLA)/poly (є-caprolactone) (PCL) blend-based bead-free electrospun nanofibrous mats (ENMs) has been carried out by using Response Surface Methodology (RSM) and Taguchi design of experiments (DoE). From the three control parameters i.e., PCL content, N, N- dimethylformamide (DMF) content, and electrospinning solution concentration, the optimal parametric combinations for minimizing the bead defects amongst ENMs were obtained. The parametric optimization outcomes remained identical, from both RSM and Taguchi approaches, irrespective of the difference in the number of experimental trials. The experimental validation of the predicted results from Taguchi-design showed an excellent agreement with >95% accuracy concerning minimization of bead defects and average fiber diameter. The solution concentration was a key determinant in controlling the gross fiber morphology. The quasi-static mechanical response of the optimally designed ENMs showed a distinct role in structural aspects of fibers. The failure responses revealed the role of the structural network of ENMs in controlling the failure stress and network collapse that was also reiterated upon the outcomes of suture retention strength assessment. The optimally designed ENM structures showed a correspondingly optimal level of suture resistance, where fine fibers offered higher resistance to suture failure due to the cooperative network effects unlike the relatively coarse fiber-based ENMs undergoing collapse attributed to fiber buckling and fiber slippage in the labile structural network.

Introduction

Electrospun nanofibrous mats (ENMs) of biodegradable polymers as biomedical devices owing to their structural similarity with the continuous networked structure of the extracellular matrix (ECM) of indigenous tissues is well reported (Sharma and Satapathy, 2019a)(Veleirinho et al., 2014)(Boakye et al., 2015)(Jun et al., 2018)(Awad et al., 2018)(Jiang et al., 2015)(Yang et al., 2018). Currently, barrier membranes are being used in regenerative therapies, such as in guided tissue regeneration/guided bone regeneration (GTR/GBR), to prevent epithelial cells and fibroblasts from occupying the defected space, by facilitating sequential tissue regeneration. The versatility of the electrospinning technique has resulted in the fabrication of ENMs using a wide range of polymeric solutions varying from biodegradable polyesters to non-biodegradable polyamides (Kim et al., 2016)(Gupta et al., 2014)(Abbasizadeh et al., 2019)(Kurpinski and Patel, 2011)(Celebioglu et al., 2017)(Carvalho et al., 2019)(Khanlou et al., 2014)(Nazir et al., 2015). Earlier, non-biodegradable membranes such as polytetrafluoroethylene (PTFE) membrane-like Cytoplast™ TXT-200 and titanium-strengthened PTEE membrane-like Cytoplast™ Ti-250 GTR were frequently used (Zhuang et al., 2019). Further, to avoid additional surgical procedures, membranes made up of biodegradable and biocompatible polymers, such as polylactic acid (PLA), poly (є-caprolactone) (PCL), and their blends or block copolymers are now being widely used in the design and development of regenerative scaffolds (Yin et al., 2016)(Valente et al., 2016)(Agarwal et al., 2008)(Mohammadian et al., 2017)(DiBalsi, 2016)(del Valle et al., 2012), vascular grafts (Meng et al., 2019), dural patches (Xie et al., 2010), and wound dressings (Karami et al., 2013). On one hand, the poor degradation stability, poor toughness of neat PLA based ENMs, while on the other high hydrophobicity and poor porosity of PCL based ENMs limit their in-vitro applications. Therefore, the blending of PLA and PCL phases in ENMs enhanced the degradation stability, strength, toughness, porosity along with a subsequent reduction in hydrophobicity of PLA/PCL blended ENMs (Karami et al., 2013)(Sharma and Satapathy, 2019b). Further, the commercially available dural grafts such as DuraGen Plus™ and TissuDura™ exhibited a regular decrease in water tightness post suture, which may lead to post-operative complications such as infections, cerebrospinal fluid (CSF) leakage, etc. (Hemstapat et al., 2020). Therefore, the evaluation and estimation, of the uniaxial tension induced failure mechanisms of electrospun membranes and their morphological dependence, remains a key concern for the researchers (Asvar et al., 2017) (Rahmati Nejad et al., 2020) (Jeffries et al., 2015). Thus, the present study unravels not only the process optimization to fabricate bead-free and ultrafine-fiber based mats but also the morphological attributes of the PLA/PCL blend based ENMs in controlling the failure under uniaxial tension at the suture site.

The electrospinning process, solution and ambient parameters, such as applied voltage, flow rate, solution concentration, solution mixture, solvent ratio, viscosity, temperature, humidity, etc., are known to influence the morphology, microstructural, thermal, and physico-mechanical properties of ENMs (Sharma and Satapathy, 2019b)(Oliveira et al., 2014)(Narayanan et al., 2015)(Sill and Recum, 2016)(Pillay et al., 2013). Nowadays, several statistical design-based and operational research-based methods are being employed to optimize the processing parameters of the ENMs. The conventional one-variable at a time (OVAT) approach to optimize a multivariable system requires numerous experimental trials and prolong time. Also, the interactive influence of the process parameters remains undetermined in the conventional approach. Thus, Response surface methodology (RSM) and Taguchi OA (orthogonal array) methods are usually employed to reduce the number of experiments and thereby reducing the time and effort involved in the optimization process (Kumar et al., 2012)(Elkasaby et al., 2018)(Asvar et al., 2017)(Moradi et al., 2018)(Nazir et al., 2015). The influence of various electrospinning process parameters on the fiber diameter and diameter variation has already been discussed in our previous publication (Sharma and Satapathy, 2020). However, systematic reports are still unavailable concerning statistical optimization/reproducibility of electrospinning solution parameters for minimizing the bead defects amongst PLA/PCL blended ENMs using RSM and Taguchi's design of experiments.

A constant set of values for process parameters such as applied voltage (~20 kV), orifice diameter (~0.5 mm), and solvent mixture (CF/DMF) have already been optimized in our previous communication, resulting in the formation of comparatively minimum fiber diameter and diameter variations (Sharma and Satapathy, 2020). In this background, the key questions that arise are what extent of variation in (a) PCL content (wt. %), (b) DMF content (wt. %) amongst PLA/PCL blended CF/DMF based solution mixture and (c) concentration of electrospinning solution will be necessary to obtain bead-free uniform ENMs. To address this concern, the present study resorts to an RSM model comprising of a set of 27 experimental trials and Taguchi L₉ OA based design of experiments (DoE) to optimally control the selected parameters for obtaining bead-free ENMs. Subsequently, Taguchi's L₉ experimental design was used to predict the precise levels of control parameters and evaluate their contribution in minimizing the bead number and fiber diameter amongst ENMs. The study further highlights the influence of morphological attributes on the structural stability of ENMs, where an enhanced structural contribution to biomedically relevant mechanical performance such as suture retention strength of PLA/PCL blend based ENMs is demonstrated.