# Diversity of Collagen Proteins and Their Biomedical Applications in Drug Delivery
## 5 Conclusions and Perspectives  
Collagen that has been conserved through evolution is found in organisms ranging from unicellular prokaryotes to multicellular eukaryotes, and even in phages and animal viruses. Furthermore, collagen is also one of the most abundant proteins in ECMs of mammalian animals and plays an important role in maintaining the biological and structural integrity of tissue as the fundamental structural component. The unique triple helical structure based on GXY repeats is what allows collagen to have the above features. Although proteins with the structural characteristics of triple helix are present in less evolved prokaryotes, most of them are not able to form fibers as collagen does in eukaryotes due to their low number of GXY repeats. Therefore, the collagens found in prokaryotes are commonly known as CLPs. Moreover, CLPs present in prokaryotes are devoid of post-translational modifications, which include hydroxylation, glycosylation, and cleavage. Type I collagen is the most abundant type among marine organisms and can be found in fish scales, skin, and bone, which are key sources of marine collagen. Compared to collagen from terrestrial animals, marine collagen has lower content of proline and hydroxyproline, which leads to low denaturing temperature and poor temperature stability. The research focus on collagen has been mainly terrestrial mammalian collagen for the past few decades, and it has been very detailed and comprehensive. The diverse supra structures, such as fibril, fiber, FACIT, and transmembrane structure, constitute the collagen superfamily, containing 29 members. In addition to its structural function, collagens play an important bioregulatory role via interacting with variable cells mediated by cell receptors and signaling pathways. Collagen-related receptors, including integrins, DDR, MRC2, etc., are involved in the regeneration and healing of tissues and organs. Because of collagen's important biological functions, mutations in its amino acid residues can cause dozens of diseases, including cancer. The diverse forms and functions of collagen in various tissues have spurred a research boom to develop new biomaterials that can deliver drugs, particularly Type I collagen. These collagens are used, alone or in combination with other materials, to develop drug delivery systems such as 3D hydrogel, nanoparticle, nanovesicle, nanofiber, nanoemulsions, nanoliposomes, film, injectable hydrogel, implantable scaffold, microsphere, and sponge. Collagen has unparalleled advantages of excellent biocompatibility, low immune response, and outstanding biodegradation in biomedical applications. It is becoming a significant material for clinical therapy and drug delivery. Targeted drug delivery, controlled release, high cellular viability, and increased bioavailability are the ways collagen-based drug delivery systems can improve clinical efficacy. Moreover, these collagen-based biomaterials are not only utilized for drug delivery but also possess biological activities that can aid in the healing of diseases. It is worth noting that collagen-based drug delivery systems present numerous challenges, including large-scale preparation, homogeneity, storage stability, controlled release mechanisms, and long-term safety. In addition, collagen has some potential limitations when it comes to its application, such as too much collagen putting pressure on the kidneys and the metal-based collagen matrix having potential cytotoxicity. To overcome these limitations, it is necessary to optimize the production process and drug delivery routes for large-scale applications. The advancement of engineering and biomaterial technology has made collagen-based products highly promising for the treatment of various diseases, drug delivery, and tissue engineering. Conceptualization, K.W. and H.D. ; writing--original draft preparation, K.W. and R.C. ; writing--review and editing, H.D. ; visualization, R.C. ; supervision, H.D. ; funding acquisition, H.D.