Tissue engineering provides a viable means of regenerating bone and skeletal muscle following injuries. Our lab has developed advanced biomaterial-based approaches to promote recovery following volumetric bone and muscle loss. To further improve biomaterial design, we focused on developing a robust understanding of heterotypic cellular interactions that are critical for healing. Specifically, both bone and skeletal muscle are highly vascularized and innervated tissues. Consequently, angiogenesis and neural infiltration are critical processes underlying their functional regeneration. Through our quantitative lightsheet microscopy platform, which can image the entire tissues at single-cell resolution, we are mapping the neurovascular associations during homeostasis, aging, and biomaterial-mediated healing to determine remaining gaps. Combined with transcriptomic approaches, this data is employed to identify novel therapeutic targets for bone and skeletal muscle.