Head and Neck Cancer (HNC) refers to tumors that originate predominantly in the mouth, nose, and throat, accounting for more than 10,000 deaths yearly in the US. Radiotherapy is a common treatment for HNC. Patients that undergo radiotherapy (RT) oftentimes develop Xerostomia (dry mouth). This is an iatrogenic disorder with no cure, which significantly impacts quality of life. Xerostomia results from irreversible damage to the salivary glands (SG), which are complex branched organs with an unmet need for regenerative therapy. RT causes apoptosis of secretory salivary acinar cells and their progenitor source in the ducts. Tissue engineering could offer a therapeutic solution by harvesting healthy SG tissue prior to RT, expanding these cells in vitro to form 3D spheroids, then creating functional tissue for implantation post-RT. During development, salivary glands form by repeated cleft and bud formation, forming a divergent, duct-to-acini architecture difficult to recapitulate with standard gel scaffolds. Recent advances in biofabrication have enabled high-resolution control over user-defined architectures within 3D tissue constructs. In this work, we leverage a subtractive manufacturing technique known as laser-based hydrogel degradation (LBHD) to guide collective epithelial morphology and exert spatiotemporal control over cell differentiation. We demonstrate the ability to carve features at high resolution within 3D tissue constructs. This thesis demonstrates the potential to direct clusters of salivary cells to migrate through the tunnels carved into hydrogels, form open lumens, and obey branching cues to form a rudimentary gland. This work has the potential to contribute to our understanding of how to create microscale glandular tissues.