Fabrication of heterogeneous porous bilayered nanofibrous vascular grafts by two-step phase separation technique

Abstract

The fabrication of porous tissue engineering scaffold made of non-water-soluble polymer commonly requires the use of porogen materials. This is complex and time-consuming, resulting in greater difficulty to prepare heterogeneous porous layered scaffold for multifunctional tissues repair, such as blood vessel and osteochondral tissue. Herein, a novel, versatile and simple one-pot dual phase separation technique is developed for the first time to fabricate porous scaffold without using porogens. Simultaneously, it also endows the resultant scaffold with the biomimetic nanofibrous architecture. Based on the easy operation of this dual phase separation technique, a facile two-step phase separation method is also put forward for the first time and applied in fabricating heterogeneous porous layered nanofibrous scaffold for tissue engineering applications.

Macroporous nanofibrous vascular scaffold with improved biodegradability and smooth muscle cells infiltration prepared by dual phase separation technique

“…As reported in our previous study, 9 PLLA/PCL composite scaffold possessed optimal porous structure when the PCL content reached to 30%. Hence, in order to maintain the proper porous structure of the composite scaffold when PLGA is introduced into the PLLA/PCL blend, PCL content in this ternary polymer blend is held constant at 30% in this study.…”

“…Then, the effect of adding PLGA on the microstructure of the composite scaffold was studied. As shown in Figure 2 and the pore diameter distribution data of PLLA/PCL 70:30 scaffold reported in our previous study, 9 all PLLA/PLGA/PCL scaffolds show spherical macroporous and nanofibrous structure and the AD is basically increased from 38.4±19.3 to 76.2±38.8 µm as PLGA content increases from 0 to 40%. These pores with the size of greater than 10 µm are deemed to be large enough for cells' infiltration.…”

“…19 Hence, we hypothesized that PLGA would be miscible with PLLA as PLCL but immiscible with PCL. Based on this hypothesis and the mechanism of dual phase separation technique developed in our previous study, 9 the ternary PLLA/PLGA/PCL solution could be separated into two phases, the polymer solution containing PLLA and PLGA with high mass fraction would serve as the continuous phase due to the mutual miscibility of PLLA and PLGA, but PCL solution with low mass fraction would serve as pore-forming phase due to its immiscibility with PLLA and PLGA (macro-phase separation) (Scheme 1). Afterward, the continuous phase containing PLLA and PLGA could gel at a low temperature and further separate into polymer-rich phase and polymer-lean phase (nanophase separation), while the pore-forming phase consisting of PCL cannot gel at the low temperature and still exists in the polymer gel by the form of liquid droplets.…”

“…Moreover, nanofibrous structure resembling native ECM is another important feature that can provide a biomimetic microenvironment for enhanced cell attachment, proliferation, and differentiation. [6][7][8] In our previous study, 9 we have developed a novel and facile dual phase separation technique to one-pot prepare macroporous and nanofibrous poly(l-lactic acid) (PLLA)/ poly(ε-caprolactone) (PCL) scaffold by phase separating the immiscible binary polymer blend solution of PLLA/PCL. However, the as-prepared PLLA/PCL composite scaffold degraded very slowly due to the inherent slow degradation rate of PLLA and PCL.…”

Geometric anisotropy on biomaterials surface for vascular scaffold design: engineering and biological advances

“…Not only that, the scaffold for vascular regeneration should be with robust mechanical properties and a large porosity enough for cell infiltration, cellcell communication and mass transportation; this two aspects of a scaffold are often opposite to each other for the fabrication. For instance, a dual-phase separation is developed recently for vascular scaffold fabrication of biomimicked nanofibrous and innterconnected porous architecture with adjustable mechanical properties, which provides favorable performance for the potential reconstruction of small diameter blood vessel [95]. Future work targeting on scaffolding an integration of properties related to the basic tissue-engineering requirements, directing ECM and cell component formation, and reconstructing correct tissue architecture is expected for the advanced development of vascular scaffold.…”