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

Biomimetic scaffolds recreating key elements of the architectureand biological activity of the extracellular matrix have enormouspotential for soft tissue engineering applications. Combining appropriatemechanical properties with select biological cues presents a challengefor bioengineering, as natural materials are most bioactive but canlack mechanical integrity, while synthetic polymers have strengthbut are often biologically inert. Blends of synthetic and naturalmaterials, aiming to combine the benefits of each, have shown promisebut inherently require a compromise, diluting down favorable propertiesin each polymer to accommodate the other. Here, we electrospun a materialcomprising chitosan, a natural polysaccharide, and polycaprolactone(PCL), one of the most widely studied synthetic polymers used in materialsengineering. In contrast to a classical blend, here PCL was chemicallygrafted onto the chitosan backbone to create chitosan-graft-polycaprolactone (CS-g-PCL) and then combined furtherwith unmodified PCL to generate scaffolds with discreet chitosan functionalization.These small amounts of chitosan led to significant changes in scaffoldarchitecture and surface chemistry, reducing the fiber diameter, poresize, and hydrophobicity. Interestingly, all CS-g-PCL-containing blends were stronger than control PCL, though withreduced elongation. In in vitro assessments, increasing the CS-g-PCL content led to significant improvements in in vitroblood compatibility compared to PCL alone while increasing fibroblastattachment and proliferation. In a mouse subcutaneous implantationmodel, a higher CS-g-PCL content improved the immuneresponse to the implants. Macrophages in tissues surrounding CS-g-PCL scaffolds decreased proportionately to the chitosancontent by up to 65%, with a corresponding decrease in pro-inflammatorycytokines. These results suggest that CS-g-PCL isa promising hybrid material comprising natural and synthetic polymerswith tailorable mechanical and biological properties, justifying furtherdevelopment and in vivo evaluation.

Automated summary

Biomimetic scaffolds that mimic the architecture and biological activity of the extracellular matrix hold great potential for soft tissue engineering. In this study, we chemically modified chitosan, a natural polysaccharide, with synthetic polymer polycaprolactone (PCL) to create chitosan-graft-polycaprolactone (CS-g-PCL). These CS-g-PCL scaffolds showed improved mechanical strength and biological properties compared to pure PCL scaffolds, including enhanced blood compatibility, cell attachment and proliferation, and decreased inflammatory response.