<p>The use of silicon nanoneedles provides a unique and versatile biointerface for a range of biomedical applications. In this work, we propose a rational design for vertical Si nanoneedles that are printed on a polymer substrate for ocular drug delivery, intracellular recording, and intra-organoid sensing. To enable minimally invasive and long-term sustained delivery of ocular drugs, we integrate vertical Si nanoneedles with a tear-soluble contact lens for ocular drug delivery. We demonstrate the effectiveness of this platform in treating corneal neovascularization in an in vivo rabbit model, surpassing the current gold standard surgical therapy. This platform has the potential to revolutionize the management of various chronic ocular diseases without causing significant side effects.</p> <p>To enable intracellular recording, we present a unique platform consisting of vertical Si nanoneedles coated with a thin, transparent network of Au-Ag nanowires. This platform is held in place and enclosed by a soft, transparent elastomer, providing simultaneous intracellular recording and live imaging with applications in neuroscience, cardiology, muscle physiology, and drug screening. To demonstrate the utility of this platform, we monitored electrical potentials from cardiomyocyte cells and cardiovascular organoids. Additionally, we propose an intra-organoid sensing platform with vertical Si nanoneedles transfer printed into a soft scaffold. This platform can be adjusted and tailored for various organoids and tumor tissues of interest, or used to deliver bioactive molecules of interest into organoids in response to external stimuli.</p> <p>Our proposed designs of vertical Si nanoneedles based platforms demonstrate their significant potential for a broad range of biomedical applications, including ocular drug delivery, intracellular recording, and intraorganoid sensing. These platforms have the potential to revolutionize current approaches and pave the way for future developments in biomedical research and clinical applications, offering new possibilities for the diagnosis and treatment of a wide range of diseases.</p>