Tailoring the multiscale architecture of electrospun membranes to promote 3D cellular infiltration.

Controlling the architecture of engineered scaffolds is of outmost importance to induce a targeted cell response and ultimately achieve successful tissue regeneration upon implantation. Robust, reliable and reproducible methods to control scaffold properties at different levels are timely and highly important. However, the multiscale architectural properties of electrospun membranes are very complex, in particular the role of fiber-to-fiber interactions on mechanical properties, and their effect on cell response remain largely unexplored. The work reported here reveals that the macroscopic membrane stiffness, observed by stress-strain curves, cannot be predicted solely based on the Young's moduli of the constituting fibers but is rather influenced by interactions on the microscale, namely the number of fiber-to-fiber bonds. To specifically control the formation of these bonds, solvent systems of the electrospinning solution were fine-tuned, affecting the membrane properties at every length-scale investigated. In contrast to dichloromethane that is characterized by a high vapor pressure, the use of trifluoroacetic acid, a solvent with a lower vapor pressure, favors the generation of fiber-to-fiber bonds. This ultimately led to an overall increased Young's modulus and yield stress of the membrane despite a lower stiffness of the constituting fibers. With respect to tissue engineering applications, an experimental setup was developed to investigate the effect of architectural parameters on the ability of cells to infiltrate and migrate within the scaffold. The results reveal that differences in fiber-to-fiber bonds significantly affect the infiltration of normal human dermal fibroblasts into the membranes. Membranes of loose fibers with low numbers of fiber-to-fiber bonds, as obtained from spinning solutions using dichloromethane, promote cellular infiltration and are thus promising candidates for the formation of a 3D tissue.

Predicting the macroscopic response of electrospun membranes based on microstructure and single fibre properties.

In the present paper, the three-dimensional structure and macroscopic mechanical response of electrospun poly(L-lactide) membranes is predicted based only on the geometry and elasto-plastic mechanical properties of single fibres supplemented by measurements of membrane weight and volume, and the resulting computational models are used to study the non-affine micro-kinematics of electrospun networks. To this end, statistical parameters describing the in-plane fibre morphology are extracted from scanning electron micrographs of the membranes, and computational network models are generated by matching the porosity of the real mats. The virtual networks are compared against computed tomography scans in terms of structure, and against uniaxial tension tests with respect to their macroscopic mechanical response. The obtained virtual network structure agrees well with the fibre disposition in real networks, and the rigorous prediction of the mechanical response of two membranes with mean diameters of 1.10µm and 0.70µm captures the experimental behaviour qualitatively. Favourable quantitative agreement, however, is obtained only after lowering the Young's moduli, yield stresses and hardening slopes determined in single fibre tests, and after reducing the density of inter-fibre bonds in the model of the membrane with thinner fibres. The simulations thus demonstrate the validity and merits of the approach to study the multi-scale mechanics of electrospun networks, but also point to potential discrepancies between the properties of electrospun fibres within a network and those produced for single fibre characterisation, and highlight the existing uncertainty on the density and quality of bonds between fibres in electrospun networks.

Polymer Membranes Sonocoated and Electrosprayed with Nano-Hydroxyapatite for Periodontal Tissues Regeneration.

Diseases of periodontal tissues are a considerable clinical problem, connected with inflammatory processes and bone loss. The healing process often requires reconstruction of lost bone in the periodontal area. For that purpose, various membranes are used to prevent ingrowth of epithelium in the tissue defect and enhance bone regeneration. Currently-used membranes are mainly non-resorbable or are derived from animal tissues. Thus, there is an urgent need for non-animal-derived bioresorbable membranes with tuned resorption rates and porosity optimized for the circulation of body nutrients. We demonstrate membranes produced by the electrospinning of biodegradable polymers (PDLLA/PLGA) coated with nanohydroxyapatite (nHA). The nHA coating was made using two methods: sonocoating and electrospraying of nHA suspensions. In a simulated degradation study, for electrosprayed membranes, short-term calcium release was observed, followed by hydrolytic degradation. Sonocoating produced a well-adhering nHA layer with full coverage of the fibers. The layer slowed the polymer degradation and increased the membrane wettability. Due to gradual release of calcium ions the degradation-associated acidity of the polymer was neutralized. The sonocoated membranes exhibited good cellular metabolic activity responses against MG-63 and BJ cells. The collected results suggest their potential use in Guided Tissue Regeneration (GTR) and Guided Bone Regeneration (GBR) periodontal procedures.