# Diversity of Collagen Proteins and Their Biomedical Applications in Drug Delivery
## 4 Collagen Application for Drug Delivery
### Delivery of Therapeutic Cells  
In clinical practice, autologous or allogeneic cell therapy has become a promising therapy. A flexible and controllable solution for treating patients with severe cutaneous defects has been developed through the development of novel keratinocyte cell-laden microcarriers prepared with biodegradable collagen [111]. To enhance cell survival in the regeneration of articular cartilage by applying stem cell therapy, the [PERSON] group developed an injectable collagen-based nanocomposite hydrogel with self-healing properties for delivering mesenchymal stem cells (MSCs) to improve cartilage regeneration. Its shear-thinning capability comes from incorporating cellulose nanocrystals (CNCs), while its self-healing and stress-relaxation behaviors were achieved by the dynamic Schiff base bonds between the aldehyde groups on a-CNCs and amine groups on collagen without any additional cross-linking agents [112]. Compared to the above injectable collagen-based hydrogels, a hydrogel based on type II collagen and activated chondro sulfate was fabricated without the addition of any catalysts or crosslinking agents. Additionally, chondrocytes were encapsulated in these hydrogels, and the hydrogels provided a favorable growth environment for cells, resulting in increased survival, better proliferation, and more robust morphology [113]. The noninvasive injection of encapsulated cell therapy (ECT) has demonstrated obvious advantages of its treatment for retinal diseases. Despite this, the therapy was still confronted with a challenge of unsteady performance and biosafety issues. A new ECT hydrogel that uses injectable composite alginate-collagen (CAC) was created to ensure safer drug delivery. The CAC ECT system presented the advantages of mechanical stability, good encapsulation power, cell viability support, multiplexed glial-cell-derived neurotrophic factor (GDNF) dosage, and compatibility with different cell types (HEK293 and ARPE-19) without immunosuppression. These features make the system an attractive, safe, and well-controlled platform for treating various eye diseases [114]. Similarly, the olfactory ectomesenchymal stem cells (OE-MSC) were encapsulated in the type I collagen hydrogel system to improve bone healing [115]. Neural stem cells (NSC) have been identified as an attractive potential therapy for treating defective neural tissues, such as the injured spinal cord. A study was conducted to investigate the recovery of the injured spinal cord through the injection of silk-collagen protein hydrogels. The novel hydrogels can protect NSC from the stress of injection and the severe inflammatory environment. The study highlights how silk-collagen hydrogels can help NSC differentiate and function, which aids in the recovery of injured spinal cord [116]. In another study, porous collagen-glycosaminoglycan scaffolds were created to administer embryonic neural stem cells for the treatment of spinal cord injury (SCI) [117]. Except for cell delivery, a novel injectable in situ-forming hydrogel (HG) based on alginate and rat tail type I collagen is developed and used as a cardiac vehicle to deliver the EVs from human adipose tissue-derived stem cells (hADSCs) for treating myocardial infarction. The HG increased the retention of the EVs for at least 7 days after intramyocardial administration [118]. In clinical practice of translation of tissue-engineered scaffolds, immune cell macrophages exhibit a significant immune response that influences the healing process depending on their particular subtypes. To effectively regulate the immune response of macrophages, a bovine type I collagen biomaterial was developed and crosslinked with genipin. The results indicated that the biotextiles improved the transformation of macrophages to subtype M2, which reduced fibrous capsule thickness and minimized the formation of granulation tissue [119]. [PERSON] Delivery of Gene Drug  
Gene [PERSON] have been a potential measure for the treatment of genetic and infectious diseases.