No abstract

Collagen is a natural polymer found abundantly in the extracellular matrix (ECM). It is easily extracted from a variety of sources and exhibits excellent biological properties such as biocompatibility and weak antigenicity. Additionally, different processes allow control of physical and chemical properties such as mechanical stiffness, viscosity and biodegradability. Moreover, various additive biomanufacturing technology has enabled layer-by-layer construction of complex structures to support biological function. Additive biomanufacturing has expanded the use of collagen biomaterial in various regenerative medicine and disease modelling application (e.g., skin, bone and cornea). Currently, regulatory hurdles in translating collagen biomaterials still remain. Additive biomanufacturing may help to overcome such hurdles commercializing collagen biomaterials and fulfill its potential for biomedicine.

Cell-derived matrices (CDM) are the decellularised extracellular matrices (ECM) of tissues obtained by the laboratory culture process. CDM is developed to mimic, to a certain extent, the properties of the needed natural tissue and thus to obviate the use of animals. The composition of CDM can be tailored for intended applications by carefully optimising the cell sources, culturing conditions and decellularising methods. This unique advantage has inspired the increasing use of CDM for biomedical research, ranging from stem cell niches to disease modelling and regenerative medicine. However, while much effort is spent on extracting different types of CDM and exploring their utilisation, little is spent on the scale-up aspect of CDM production. The ability to scale up CDM production is essential, as the materials are due for clinical trials and regulatory approval, and in fact, this ability to scale up should be an important factor from the early stages. In this review, we first introduce the current CDM production and characterisation methods. We then describe the existing scale-up technologies for cell culture and highlight the key considerations in scaling-up CDM manufacturing. Finally, we discuss the considerations and challenges faced while converting a laboratory protocol into a full industrial process. Scaling-up CDM manufacturing is a challenging task since it may be hindered by technologies that are not yet available. The early identification of these gaps will not only quicken CDM based product development but also help drive the advancement in scale-up cell culture and ECM extraction.