Many different cancers result in bone metastases, which cause a variety of complications that are often incurable. Cancer cells interact with the bone environment and experience molecular reprogramming. Understanding and analyzing cell activity, including that of tumor growth and bone remodeling, could help to develop preclinical research and clinical interventions for these cancers. In this project, we use a 3D, time-resolved analysis of bone cancer models using multi-parametric intravital multiphoton microscopy (iMPM). This technique is a powerful method of analysis in soft tissues, but is limited in imaging cellular activity in native bones. Such bone tissue may be difficult to optically access due to bone thickness, causing light scattering, and the complex topology of bone. To overcome these challenges, tissue engineering can be used to create a well-defined, fully intact bone (miniaturized tissue-engineered bone construct, mTEBC) that can be implanted subcutaneously to observe mechanisms of cancer metastasis via iMPM via an optical skin window, 3D printed scaffolds, specifically melt-electrospinning writing (MESW), can provide a scaffold customized to support bone mimetic environment (BME) generation, demonstrated in Figure 1. In addition, these MESW scaffolds combined with the iMPM can be used to study other phenomena relevant to tissue engineering, medical devices, and fabricated complex tissues for implantation via the real-time imaging of foreign body response to custom designed biomaterial devices.