# Diversity of Collagen Proteins and Their Biomedical Applications in Drug Delivery
## 4 Collagen Application for Drug Delivery
### Delivery of Protein and Peptide Drug  
Bone morphogenetic protein 2 (BMP2) is a crucial osteogenic factor that promotes bone formation by stimulating osteoblast differentiation. A bone repair biomaterial (HC-COL-BMP-2) was developed by the tilapia skin collagen crosslinked with heparin to specifically bind to BMP-2. The prepared HC-COL has no cytotoxicity, shows enough thermal stability, and improves the binding of BMP-2 to cure bone repair by inducing MC3T3-E1 cells with higher activity [102]. Extracellular vesicles (EVs) have received increasing attention in various areas of regenerative medicine over the past decade. Royal jelly EVs (RJ EVs) have been shown to have beneficial wound-healing properties by promoting the migration of mesenchymal stem cells and preventing the formation of pathogen biofilms [103]. Herein, RJ EVs and fibroblasts were integrated into type I collagen gel to achieve sustainable release of RJ EVs. The continuous delivery matrix made of 2 mg/mL type I collagen showed a significant potential for wound-healing therapies [104]. The treatment of bone defects like osteoporosis, arthritis, and fractures can be achieved through the use of both the bioactive molecule BMP-2 and the chemical agent \(\mathrm{Aln}\), which are both approved clinical drugs. Since the studies had verified that the combined application of BMP-2 and \(\mathrm{Aln}\) for bone treatment had no additive effects on bone regeneration, the [PERSON] group developed a collagen-hydroxyapatite scaffold-loading BMP-2 protein and micromolecular \(\mathrm{Aln}\) to enhance bone regeneration by releasing them in a sequential manner in the rat bone defect model. Rat tail-derived collagen type I is the source of collagen composition. The delivery system indicated an initial release of BMP-2 for a few days, followed by the sequential release of \(\mathrm{Aln}\) after two weeks [105]. The preferred healing protein for bone defects is bone morphogenetic protein-2 (BMP-2), but BMP-7 is also a common substitute for bone grafts. In this research, the bovine type I collagen was used as the crucial composition to establish a collagen-hydroxyapatite (CHA) scaffold delivery system to compare the effect of BMP-2 homodimer and BMP-2/7 heterodimer on the osteoinductive's potential. The CHA scaffold delivered both protein dimers for at least 20 days, resulting in decreased doses of physiological growth factors for bone fracture healing [106]. Inducing angiogenesis in ischemic tissues has a positive impact on treating myocardial infarction (MI) and stroke. In a study, porcine collagen type I was blended with alginate to form the hydrogel microsphere with angiogenic factor FGF-2. The microsphere showscomplete biocompatibility and no adverse reactions when injected into mice. Furthermore, it has demonstrated the robust induction of angiogenesis in zebrafish embryos [107]. Meniscus tears are a common knee injury that further leads to arthritis. The reconstruction of the meniscus using artificial materials is an effective measure. A novel collagen nanofiber scaffold prepared by acid-soluble bovine collagen type I and harboring heparin was fabricated by electrospinning and could sustainably release three factors: PDGF-BB, TGF-81, and CTGF. These factors integrated into collagen nanofibers resulted in their sustained release, which increased synovial cell viability, proliferation, and migration, and enhanced the regeneration of meniscal tissue [108]. The development of next-generation antibody drugs has become more attractive with the advent of nanoantibody technology. To deliver the nanoantibody to the targeted cancer, the hydrogels consisting of the cross-linking of tilapia skin collagen and chitosan were developed to deliver and release nanoantibodies 2D5 and KPU for the treatment of cancer [109]. Extracellular beta-amyloid (A\(\beta\)) plaques or intraneuronal tau tangles in the brain are the cause of Alzheimer's disease (AD). An effective therapeutic strategy aims to prevent or clear these A\(\beta\) plaques by degrading the enzyme neprilysin.