Dual electrospinning with sacrificial fibers for engineered porosity and enhancement of tissue ingrowth

Abstract

Porosity, pore size and pore interconnectivity are critical factors for cellular infiltration into electrospun scaffolds. This study utilized dual electrospinning with sacrificial fiber extraction to produce scaffolds with engineered porosity and mechanical properties. Subsequently, scaffolds were covalently grafted with heparin, a known anti-coagulant with growth-factor binding properties. We hypothesized that the tissue ingrowth would correlate positively with the porosity of the scaffolds. Pellethane® (PU) was spun simultaneously with poly(ethylene oxide) (PEO, subsequently extracted). Low, medium and high porosity scaffolds and heparinized versions of each were characterized and implanted in vivo for evaluation of cellular infiltration and inflammation subcutaneously in male Wistar rats (7,14 and 28 days, n = 6). Average pore-size for low (76 ± 0.2%), medium (83 ± 0.5%) and high (90 ± 1.0%) porosity scaffolds was 4.0 ± 2.3 µm, 9.9 ± 4.2 µm and 11.1 ± 5.5 µm (p < 0.0001). Heparinization resulted in increased fiber diameter (3.6 ± 1.1 µm vs. 1.8 ± 0.8 µm, p < 0.0001) but influenced neither pore-size (p = 0.67) nor porosity (p = 0.27). Cellular infiltration for low, medium and high porosity scaffolds reached 33 ± 7%, 77 ± 20% and 98 ± 1% of scaffold width, respectively, by day 28 of implantation (p < 0001); heparinization did not affect infiltration (p = 0.89). The ultimate tensile strength (UTS) and Young's modulus (E ) of the constructs increased linearly with increasing PU fiber fraction (UTS: r = 0.97, p < 0.0001, E : r = 0.76, p < 0.0001) and heparinization resulted in decreased strength but increased stiffness compared to non-heparinized scaffolds. Increased PEO to PU fraction in the scaffold resulted in predictable losses to mechanical strength and improvements to cellular infiltration, which could make PEO to PU fraction a useful optimization parameter for small diameter vascular grafts. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 105B: 1559-1572, 2017.

Full cell infiltration and thick tissue formationin vivoin tailored electrospun scaffolds

“…The expansion in size would still allow for a thick layer of tissue to form. Others have also reported a slight change in scaffold size after implantation [19] , but not as significant of an increase as we report here. Scaffold properties such as fiber stiffness and strength of inter-fiber connections could, among others, potentially influence this expansion in size.…”

“…Many ESP scaffolds only allow limited infiltration of 200-400 μ m [15, 16] . Using PEG fibers, others have shown infiltration of tissue up to 1 m m [17, 19] . The greatest infiltration of tissue in ESP scaffolds reported in literature is of 1.3 mm thick scaffolds, using PEG microparticles [20] .…”

“…However, tissue infiltration in vivo has been limited to approximately 1 mm scaffold thickness. Increasing infiltration in a reliable and reproducible manner in scaffolds thicker than 1 mm remains a challenge [17, 19] .…”

Progressive Reinvention or Destination Lost? Half a Century of Cardiovascular Tissue Engineering

“…The minimal dimensions of such spaces were well defined at 80-400 µm 2 (102, 356) optimally even being as large as 5,000-6,000 µm 2 (357). Therefore, if transmural endothelialisation and healing is the goal, this requirement would exclude the use of ePTFE of <60µm internodal distance, woven Dacron and most of the electrospun polyurethane grafts unless their scaffold structures were manipulated to increase the interfibrillar spaces (357)(358)(359)(360)). Yet, making transmural endothelialisation of synthetic scaffolds a reliable occurrence also requires the suppression of the surface compaction with interstitial thrombus (107) (Figure 14).…”

Biomaterials in Tendon and Skeletal Muscle Tissue Engineering: Current Trends and Challenges

“…For these reasons, some researchers have been working on modified electrospun set-up devices in order to produce improved scaffolds with high porosity and a 3D structure. Sacrificial fibers [ 138 ], air-gap [ 139 ], water bath collection [ 107 , 140 , 141 ], or twisted electrospinning to make yarns [ 35 , 107 , 141 ], have appeared to be a promising solution to confer electrospun scaffolds a superior ultrastructure.…”