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One of the main challenges in biofabrication of tissues and organs is the development of biomimetic scaffolds that replicate the complex architecture of native tissue, including 3-D vasculature. Tissue decellularization can be used for obtaining such scaffolds, however, current techniques require the use of chemical and biological agents, often in combination with physical force, which can result in chemical alteration to the matrix. Moreover, such decellularization can only be performed ex vivo and the engineered tissue or organ would require cultuvation in vitro and further surgical transplantation. Recently developed boiling histotripsy (BH) technology uses millisecond-long pulses of focused ultrasound waves with high amplitude shock fronts to selectively fractionate tissue into subcellular debris without thermal effect. This technology has shown great potential to decellularize unwanted tissue in vivo inside the body, through the skin, while leaving collageneous structures such as vessels at least grossly intact. Here we report the results of pilot acute studies on transcutaneous volumetric BH ablation of porcine liver and kidney tissues demonstrating potential capabilities of such technology for noninvasive tissue decellularization toward organ biofabrication in vivo.