Evaluation of the Immune Response to Chitosan--poly(caprolactone) Biopolymer Scaffolds.

Biomimetic scaffolds recreating key elements of the architecture and biological activity of the extracellular matrix have enormous potential for soft tissue engineering applications. Combining appropriate mechanical properties with select biological cues presents a challenge for bioengineering, as natural materials are most bioactive but can lack mechanical integrity, while synthetic polymers have strength but are often biologically inert. Blends of synthetic and natural materials, aiming to combine the benefits of each, have shown promise but inherently require a compromise, diluting down favorable properties in each polymer to accommodate the other. Here, we electrospun a material comprising chitosan, a natural polysaccharide, and polycaprolactone (PCL), one of the most widely studied synthetic polymers used in materials engineering. In contrast to a classical blend, here PCL was chemically grafted onto the chitosan backbone to create chitosan--polycaprolactone (CS--PCL) and then combined further with unmodified PCL to generate scaffolds with discreet chitosan functionalization. These small amounts of chitosan led to significant changes in scaffold architecture and surface chemistry, reducing the fiber diameter, pore size, and hydrophobicity. Interestingly, all CS--PCL-containing blends were stronger than control PCL, though with reduced elongation. In in vitro assessments, increasing the CS--PCL content led to significant improvements in in vitro blood compatibility compared to PCL alone while increasing fibroblast attachment and proliferation. In a mouse subcutaneous implantation model, a higher CS--PCL content improved the immune response to the implants. Macrophages in tissues surrounding CS--PCL scaffolds decreased proportionately to the chitosan content by up to 65%, with a corresponding decrease in pro-inflammatory cytokines. These results suggest that CS--PCL is a promising hybrid material comprising natural and synthetic polymers with tailorable mechanical and biological properties, justifying further development and in vivo evaluation.