Ruchi Birur

Decellularized tissue possesses significant regenerative potential, yet fabricating complex extracellular matrix (ECM) scaffolds remains challenging. Blending with synthetic polymers aids ECM fabrication but often relies on digested ECM, and encapsulation within the synthetic matrix can limit cell‐ECM interactions. We recently developed a suspension electrospinning platform to facilitate ECM fabrication without digestion or polymer‐carriers. Its integration into a co‐electrospinning system enables modular design of composite scaffolds, combining ECM's regenerative potential with the advantages of synthetic polymers. This study compares co‐electrospinning and blend electrospinning of polycaprolactone and small intestinal submucosa (SIS) for use as a bone wrap to augment membrane durability, sustain infection control, and enhance vascularity in Masquelet's induced membrane technique. Co‐spun wraps improve handling properties compared to ECM wraps; solvent welding is used to achieve target suture retention standards without diminishing SIS content. Unlike blended wraps, co‐spun wraps support full‐thickness cell infiltration within 4 weeks, release gentamicin at bactericidal concentrations for 6 weeks, and demonstrate angiogenic properties. Co‐spun wraps achieve full tissue integration and enhanced membrane vascularity in an in vivo subcutaneous rat model for 6 weeks. These findings highlight the functionality of a co‐electrospinning modular design and the efficacy of using a co‐spun wrap in bone tissue engineering applications.

Decellularized tissue possesses significant regenerative potential, yet fabricating complex extracellular matrix (ECM) scaffolds remains challenging. Blending with synthetic polymers can aid ECM fabrication but often relies on digested ECM and encapsulation within the synthetic matrix can limit cell-ECM interactions. We recently developed a suspension electrospinning platform to facilitate ECM scaffold fabrication without the need for digestion or polymer-carriers. Its integration into a co- electrospinning system enables modular design of composite scaffolds to combine the regenerative potential of ECM with the advantages of synthetic polymers. This study directly compares co- electrospinning and blend electrospinning of polycaprolactone and small intestinal submucosa (SIS) for use as a bone wrap to augment membrane durability, sustain infection control, and enhance vascularity in Masquelet’s induced membrane technique. Co-spun wraps demonstrated improved handling properties as compared to ECM wraps and solvent welding was used to achieve target suture retention standards without diminishing SIS content. Unlike the blended wraps, the co-spun wraps supported full-thickness cell infiltration within 4 weeks, released gentamicin at a bactericidal concentration for 6 weeks, and demonstrated enhanced angiogenic properties. Collectively, these findings highlight the functionality of a co-electrospinning modular design and demonstrate the efficacy of using a co-spun wrap in bone tissue engineering applications.

Decellularized extracellular matrices (dECM) have strong regenerative potential as tissue engineering scaffolds; however, current clinical options for dECM scaffolds are limited to freeze-drying its native form into sheets. Electrospinning is a versatile scaffold fabrication technique that allows control of macro- and microarchitecture. It remains challenging to electrospin dECM, which has led researchers to either blend it with synthetic materials or use enzymatic digestion to fully solubilize the dECM. Both strategies reduce the innate bioactivity of dECM and limit its regenerative potential. Herein, we developed a new suspension electrospinning method to fabricate a pure dECM fibrous mesh that retains its innate bioactivity. Systematic investigation of suspension parameters was used to identify critical rheological properties required to instill "spinnability," including homogenization, concentration, and particle size. Homogenization enhanced particle interaction to impart the requisite elastic behavior to withstand electrostatic drawing without breaking. A direct correlation between concentration and viscosity was observed that altered fiber morphology; whereas, particle size had minimal impact on suspension properties and fiber morphology. The versatility of this new method was demonstrated by electrospinning dECM with three common decellularization techniques (Abraham, Badylak, Luo) and tissue sources (intestinal submucosa, heart, skin). Bioactivity retention after electrospinning was confirmed using cell proliferation, angiogenesis, and macrophage polarization assays. Collectively, these findings provide a framework for researchers to electrospin dECM for diverse tissue engineering applications.