Collagen is a principal protein present in the extracellular matrix of all animals. Collagen has a diverse application in the tissue regeneration process due to its biocompatibility and functional versatility. In this chapter, we focused on upstream and downstream processes for scalable collagen production and its application in scaffold fabrication in cornea and bone grafts, highlighting the selection of raw materials and economic analysis of the process. Since there are various types of collagens present in different parts of tissues, the establishment of a standardized protocol for collagen extraction and purification becomes a challenging part. However, combining physical, chemical, and biological methods and optimization at different parameters of temperature, pH, etc., makes these processes more efficient. Precision fermentation offers an alternative production method to enhance the collagen quality and yield, reduced costs, and processing time, thus giving better control over the scalable fermentation process. Key concerns such as maintaining the degree of purity and resolution quality attained by chromatography at the laboratory scale must be addressed to assess the impact of the scale-up process while complying with the Good Manufacturing Practices (GMP) guidelines. Collagen-comprised biomaterials are ideal for bone repair and corneal transplantation, providing a foundation for neural regeneration and repair. Future bioprocessing advancements may increase productivity, lower costs, and expand collagen’s use across various biomedical applications.