Native human collagen type I provides a viable physiologically relevant alternative to xenogeneic sources for tissue engineering applications: A comparative in vitro and in vivo study

Abstract

Xenogeneic sources of collagen type I remain a common choice for regenerative medicine applications due to ease of availability. Human and animal sources have some similarities, but small variations in amino acid composition can influence the physical properties of collagen, cellular response, and tissue remodeling. The goal of this work is to compare human collagen type I‐based hydrogels versus animal‐derived collagen type I‐based hydrogels, generated from commercially available products, for their physico‐chemical properties and for tissue engineering and regenerative medicine applications. Specifically, we evaluated whether the native human skin type I collagen could be used in the three most common research applications of this protein: as a substrate for attachment and proliferation of conventional 2D cell culture; as a source of matrix for a 3D cell culture; and as a source of matrix for tissue engineering. Results showed that species and tissue specific variations of collagen sources significantly impact the physical, chemical, and biological properties of collagen hydrogels including gelation kinetics, swelling ratio, collagen fiber morphology, compressive modulus, stability, and metabolic activity of hMSCs. Tumor constructs formulated with human skin collagen showed a differential response to chemotherapy agents compared to rat tail collagen. Human skin collagen performed comparably to rat tail collagen and enabled assembly of perfused human vessels in vivo. Despite differences in collagen manufacturing methods and supplied forms, the results suggest that commercially available human collagen can be used in lieu of xenogeneic sources to create functional scaffolds, but not all sources of human collagen behave similarly. These factors must be considered in the development of 3D tissues for drug screening and regenerative medicine applications.

Species-Based Differences in Mechanical Properties, Cytocompatibility, and Printability of Methacrylated Collagen Hydrogels

“…Cell viability results revealed that both collagen species and photoinitiator choice significantly impact the viability and metabolic activity of human MSCs encapsulated in CMA hydrogels (Figures and ). Human MSCs encapsulated in CMA hydrogels cross-linked using LAP demonstrated significantly greater ( p < 0.05) cytocompatibility than I-2959, which was consistent with previously published reports. , Species-based differences revealed that rat CMA was more cytocompatible than bovine CMA; a finding consistent with a recent publication that compared different species of collagen . Higher cell viability and metabolic activity in rat CMA hydrogels may be attributed to greater matrix stiffness of rat CMA compared to bovine CMA counterparts …”

“…41,42 Species-based differences revealed that rat CMA was more cytocompatible than bovine CMA; a finding consistent with a recent publication that compared different species of collagen. 18 Higher cell viability and metabolic activity in rat CMA hydrogels may be attributed to greater matrix stiffness of rat CMA compared to bovine CMA counterparts. 43 3D bioprinting is an additive biofabrication methodology that allows for the development of complex biological structures for use in tissue replacement/regeneration applications.…”

“…Results from this study agree with prior work which demonstrated that bovine and human collagen were shown to exhibit greater hydrogel stability than other species examined (Figure ). The extraction method used to obtain the collagen may have influenced these stability results. The initial exposure of rat collagen to acid during the extraction process may have weakened some of the peptide bonds in the collagen molecule, thus making the rat CMA (telo) more susceptible than bovine and human CMA (atelo) to degradation by the action of the collagenase enzyme which targets these same peptides. , …”

“…In addition, differences in isolation methods (i.e., acid extraction vs enzymatic digestion) yield collagen protein with structural disparities with (telo) and without (atelo) the telopeptide ends which can also impact the properties of CMA. While prior studies have investigated the effects of different species and isolation techniques on properties of collagen hydrogels, − how these innate structural differences impact the physiochemical properties of CMA is unknown. In addition, changes in compositional and mechanical properties of CMA can also influence cell behavior and its applicability as a bioink for 3D printing applications.…”

Adipose Mesenchymal Stem Cell Derived Exosomes Promote Keratinocytes and Fibroblasts Embedded in Collagen/Platelet‐Rich Plasma Scaffold and Accelerate Wound Healing

“…[3,4] Type-I collagen (COL-I) has a natural 3D network with a porous ultrastructure and has similar mechanical properties to skin soft tissue; furthermore, the biocompatibility and elasticity can provide favorable biomaterial-cell interactions, which can induce cell adhesion and migration and ECM deposition, thus driving wound regeneration and repair. [5][6][7] Nevertheless, obtaining bioscaffold materials with sufficient regenerative potential remains challenging for clinicians. [8] Inability to revascularize is another limitation of the current skin substitutes, and cells in the substitute die and slough away from the scaffolds with limited blood supply.…”