Fabrication and evaluation of biomimetic-synthetic nanofibrous composites for soft tissue regeneration

Abstract

Electrospun scaffolds hold promise for the regeneration of dense connective tissues, given their nanoscale topographies, provision of directional cues for infiltrating cells and versatile composition. Synthetic slow-degrading scaffolds provide long-term mechanical support and nanoscale instructional cues; however, these scaffolds suffer from a poor infiltration rate. Alternatively, nanofibrous constructs formed from natural biomimetic materials (such as collagen) rapidly infiltrate but provide little mechanical support. To take advantage of the positive features of these constructs, we have developed a composite scaffold consisting in both a biomimetic fiber fraction (i.e., Type I collagen nanofibers) together with a traditional synthetic (i.e., poly-[ε-caprolactone], PCL) fiber fraction. We hypothesize that inclusion of biomimetic elements will improve initial cell adhesion and eventual scaffold infiltration, whereas the synthetic elements will provide controlled and long-term mechanical support. We have developed a method of forming and crosslinking collagen nanofibers by using the natural crosslinking agent genipin (GP). Further, we have formed composites from collagen and PCL and evaluated the long-term performance of these scaffolds when seeded with mesenchymal stem cells. Our results demonstrate that GP crosslinking is cytocompatible and generates stable nanofibrous type I collagen constructs. Composites with varying fractions of the biomimetic and synthetic fiber families are formed and retain their collagen fiber fractions during in vitro culture. However, at the maximum collagen fiber fractions (20%), cell ingress is limited compared with pure PCL scaffolds. These results provide a new foundation for the development and optimization of biomimetic/synthetic nanofibrous composites for in vivo tissue engineering.

Synthetic/Biopolymer Nanofibrous Composites as Dynamic Tissue Engineering Scaffolds

“…As outlined above, we have demonstrated that both silk and collagen can be co-spun with synthetic nanofibers to create biopolymer composites with both mechanical integrity and flexibility in post-processing [72,96,173]. Collagen/PCL nanofiber composites are more biomimetic than pure PCL and can improve the initial cellularity of composites [173].…”

“…As outlined above, we have demonstrated that both silk and collagen can be co-spun with synthetic nanofibers to create biopolymer composites with both mechanical integrity and flexibility in post-processing [72,96,173]. Collagen/PCL nanofiber composites are more biomimetic than pure PCL and can improve the initial cellularity of composites [173]. The Wagner group also established that multifiber mats can be functionalized to release drugs or growth factors by using one family to act as a stable template (PEUU nanofibers), while a second family (PLGA) can be used to deliver active antibiotics [42].…”

Biohybrid Fibro-Porous Vascular Scaffolds: Effect of Crosslinking on Properties

“…Tubular scaffolds (5 cm long) were immersed in a HuBiogel solution (1 mg/mL in the phosphate buffered saline, PBS) for 24 h and then kept at 37 °C for 2 h for gelation. Crosslinking of proteins using both Gp and EDC was carried out in solution-phase [6, 12]. Scaffolds were soaked in 200 mM solutions of Gp in pure ethanol or EDC in pure ethanol for 24 h. After crosslinking the mechanical, structural, and morphological characterization, as well as coating stability studies, were carried out for PCL/PGC, biohybrid (HB coated), and crosslinked scaffolds.…”

Biodegradable polymeric nanomaterials

“…Indeed for fibre-based materials, the mechanical properties are affected by the polymer molecular weight, morphology, crystallinity, as well as the material size and shape such as porosity, pore area and fibre size, density and orientation [44]. For instance, when electrospun fibre-based materials are developed with aligned fibres, the modulus and the tensile strength increase and the mechanical behaviour becomes anisotropic in comparison to randomly arranged fibres [62,63]. The fibre size also affects the mechanical properties as a reduction in the size improves the orientation and decreases the quantity of defects in the structure.…”