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In vitro and in vivo 3D (Bio)Printing for Treatment of Musculoskeletal Injuries

Azadeh Mostafavi, University of Nebraska - Lincoln

Abstract

Musculoskeletal defects are commonly caused by traumatic injuries and tumor removal and critically sized defects overwhelm the regenerative capacity of the native tissue. Reparative strategies such as auto, xeno, and allografts have proven to be insufficient to reconstruct and regenerate these defects. In one study, for the first time, we introduce the use of handheld melt spun three dimensional (3D) printers to in vivo print scaffolds aiming at bone defect reconstruction. Engineered composite filaments were generated from poly(caprolactone) (PCL) doped with zinc oxide nanoparticles and hydroxyapatite microparticles. The use of PCL-based materials allowed low-temperature printing to avoid overheating of the surrounding tissues. The in situ printed scaffolds showed moderate adhesion to wet bone tissue, which can prevent scaffold dislocation. The printed scaffolds showed to be osteoconductive and supported the osteodifferentiation of mesenchymal stem cells. Biocompatibility of the scaffolds upon in vivo printing subcutaneously in mice showed promising results. In another study, to address the muscle injury treatments, a nanoengineered GelMA hydrogel is used as bioink for the in vivo formation of an adhesive and 3D scaffold through a partially automated handheld printer in volumetric muscle loss (VML) injuries for muscle regeneration. While significant functional recovery was observed by modulation of the remnant muscle, poor cell spreading, proliferation, and migration limited the rapid tissue regeneration. To overcome these limitations, a simple, affordable but robust strategy is utilized to generate foam bioinks through one-step mechanical agitation. Upon crosslinking, a multiscale interconnected porous structure is formed. The effect of process parameters on the pore size distribution and mechanical and rheological properties of the bioinks is determined. The developed foam bioinks can be easily printed using conventional stationery and custom-built handheld bioprinters. It is demonstrated that the adhesive foam bioinks are biocompatible and enhanced cellular growth and spreading. The subcutaneous and VML model implantation of scaffolds formed from the engineered foam bioinks showed their rapid integration, vascularization, and superior functional recovery in comparison to their hydrogel counterparts.

Subject Area

Biomedical engineering|Engineering

Recommended Citation

Mostafavi, Azadeh, "In vitro and in vivo 3D (Bio)Printing for Treatment of Musculoskeletal Injuries" (2021). ETD collection for University of Nebraska - Lincoln. AAI28490549.
https://digitalcommons.unl.edu/dissertations/AAI28490549

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