Collagen fibril formation in vitro: From origin to opportunities

Sometimes, to move forward, it is necessary to look back. Collagen type I is one of the most commonly used biomaterials in tissue engineering and regenerative medicine. There are a variety of collagen scaffolds and biomedical products based on collagen have been made, and the development of new ones is still ongoing. Materials, where collagen is in the fibrillar form, have some advantages: they have superior mechanical properties, higher degradation time and, what is most important, mimic the structure of the native extracellular matrix. There are some standard protocols for the formation of collagen fibrils in vitro, but if we look more carefully at those methods, we can see some controversies. For example, why is the formation of collagen gel commonly carried out at 37 ​°C, when it was well investigated that the temperature higher than 35 ​°C results in a formation of not well-ordered fibrils? Biomimetic collagen materials can be obtained both using culture medium or neutralizing solution, but it requires a deep understanding of all of the crucial points. One of this point is collagen extraction method, since not every method retains the ability of collagen to reconstitute native banded fibrils. Collagen polymorphism is also often overlooked in spite of the appearance of different polymorphic forms during fibril formation is possible, especially when collagen blends are utilized. In this review, we will not only pay attention to these issues, but we will overview the most prominent works related to the formation of collagen fibrils in vitro starting from the first approaches and moving to the up-to-date recipes. [Display omitted]