Table 2.
Overview of the Animal Models and Experimental Parameters Used to Study Host Response and Wound Healing Associated with Cross-Linked Collagen-Based Materials
| Model size | Species | Material | Model | Time points | Characterization | References |
|---|---|---|---|---|---|---|
| Small animal models | C57BL/6 mouse | Dermal sheep collagen disk (GTA, HMDI) | Subcutaneous implantation | 2, 7, 14, and 21 days | Toluidine blue staining, PCR (IL-4, IL-6, IL-10, IL-13, IFN-γ, TGF-β, MCP-1, MIP-1), IHC (IL-10), in situ zymography | 21,168 |
| Sprague-Dawley rat | Porcine bladder (EDC, GTA), porcine heart valve (GTA), bovine pericardium (GTA) | Subcutaneous implantation | 7, 28, 63, and 180 days | HE and MT staining, quantitative stereological analysis | 143,150 | |
| Sprague-Dawley rat | SIS (EDC, noncross-linked), porcine dermis (EDC, unknown, noncross-linked), | Partial-thickness defect in abdominal muscle | 7, 14, 28, 112 days | MT staining and IHC (CD68, CD80, CD163, CCR7) | 20,148 | |
| Wistar rat | Bovine pericardium (GTA, noncross-linked) | Partial-thickness defect in abdominal muscle | 21 and 90 days | HE and MT staining, IHC (CD80, CD163), lymphocyte transformation test | 159 | |
| Sprague-Dawley rat | Porcine dermis (EDC, HMDI) and human dermis (noncross-linked) | Partial-thickness defect in abdominal muscle | 3, 7, 14, 30, 90, and 180 days | HE, MT, and Verhoeff's staining, IF (COLI, COLIII, FN, elastase, and MMP-9) | 151 | |
| Sprague-Dawley rat | Collagen hydrogel with or without growth factors | Full-thickness skin defect | 3, 7, and 14 days | HE staining, IHC (CD68, COLIV), quantitative stereological analysis, wound contraction | 144,145 | |
| Large animal models | New Zealand white rabbit | Porcine dermis (EDC, HMDI) and SIS (noncross-linked) | Partial-thickness defect in abdominal oblique muscle | 14, 30, 90, and 180 days | MT staining, IF, and qRT-PCR for COLI and COLIII, tensile test | 165,166 |
| New Zealand white rabbit | Collagen sponge with or without growth factors | Second-degree burn defect | 15 days | HE staining, tensile test | 146 | |
| Yucatan minipig | Porcine dermis (EDC, HMDI), bovine pericardium (noncross-linked), and human dermis (noncross-linked) | Full-thickness defect in abdominal muscle | 30, 180, and 360 days | HE staining, stereological analysis, tensile test | 149,158 | |
| Caribbean vervet monkey | Porcine dermis (EDC, HMDI) and SIS (noncross-linked) | Full-thickness defect in abdominal muscle | 180 days | HE staining, IHC (CD3, CD20, CD68), ELISA (immunoglobulin G and M), tensile test | 138,167 |
COL I, collagen type I; ELISA, enzyme-linked immunosorbent assay; HE, hematoxylin and eosin; IF, immunofluorescence; IFN-γ, interferon gamma; IHC, immunohistochemistry; IL, interleukin; MCP-1, monocyte chemoattractant protein-1; MIP-1, macrophage inflammatory protein-1; MT, Masson's trichrome; PCR, polymerase chain reaction; SIS, small intestinal submucosa; TGF-β, transforming growth factor beta.