# Diversity of Collagen Proteins and Their Biomedical Applications in Drug Delivery
## 1 Introduction  
The physical integrity of cells is greatly impacted by the extracellular matrix (ECM), which involves proliferation, differentiation, migration, and adhesion. Collagen, which belongs to the fibrous protein family, is the oldest and most abundant ECM protein in all connective tissues such as skin, ligaments, tendons, muscles, blood vessels, bone, cartilage, or cornea. It has a molecular weight of around 300 kDa, a diameter of about 1.4 nm, and an approximate length of 280 nm [1]. Up to now, totals of 29 distinct types of collagens, named with Roman number I-XXIX in chronological order of discovery, have been identified which are coded by at least 45 different genes [2]. The classification of collagens is based on their domain and structural complexity. Each collagen contains its own unique alpha chain with its own domain structure. The most abundant among the 29 isoforms of collagen is type I (principally in the skin, tendons, muscles, and bone), type II (in cartilage), type III (often found alongside type I), and type IV (at the basement membrane). Collagen protein is composed of triple-helical polypeptide chains and contains the repeating sequence (Gly-X-Y)n with Pro often located at positions X and Y. Such triple-helical structures are important for the biological function of collagen, such as the elasticity and waterproofness of the skin, the structural stability of connective tissue cells, wound healing, and bone repair.  
Generally, collagens prepared from different animals such as bovine, porcine, equine, and marine organisms have been widely used as biomaterials for hemostasis, stimulatory,drug delivery, plastic surgery, bone defect, and tissue engineering, which is also named collagen-based biomaterials (CBBs). In addition, although collagen or collagen peptides have been produced recombinantly by transgenic organisms, such as _E. coli_, yeast, and mammalian cells, their wide application is hindered by their lower yields and higher cost. Furthermore, the heterologous expression cannot achieve the post-translational modifications of glycosylation and hydroxylation on proper Pro and Lys residues, as well as heterotrimic compositions. Therefore, it is obvious that natural collagens will remain the major source of CBBs in the future [3]. In contrast to terrestrial mammalian collagens, marine collagens have obvious advantages concerning safe, easy obtain, no adverse inflammatory reactions, and no immunologic responses. As a result, marine collagens are a promising source for pharmaceutical applications. Herein, the primary focus of this article is on the wide variety of collagen found in prokaryotes, eukaryotes, marine, and terrestrial organisms, as well as its structural and functional diversification, and the genetic disorders that are connected to collagen. These diseases are closely linked to the signaling pathways involved in collagen receptors. The article further focuses on the use of collagen in drug delivery, including small molecule chemotherapeutics, protein and peptide drugs, therapeutic cellular and gene-based drugs, demonstrating the wide range of uses of collagen in the treatment of diseases.