Acellular and cellular high-density, collagen-fibril constructs with suprafibrillar organization

Abstract

Collagen is used extensively for tissue engineering due to its prevalence in connective tissues and its role in defining tissue biophysical and biological signalling properties. However, traditional collagen-based materials fashioned from atelocollagen and telocollagen have lacked collagen densities, multi-scale organization, mechanical integrity, and proteolytic resistance found within tissues in vivo. Here, highly interconnected low-density matrices of D-banded fibrils were created from collagen oligomers, which exhibit fibrillar as well as suprafibrillar assembly. Confined compression then was applied to controllably reduce the interstitial fluid while maintaining fibril integrity. More specifically, low-density (3.5 mg mL(-1)) oligomer matrices were densified to create collagen-fibril constructs with average concentrations of 12.25 mg mL(-1) and 24.5 mg mL(-1). Control and densified constructs exhibited nearly linear increases in ultimate stress, Young's modulus, and compressive modulus over the ranges of 65 to 213 kPa, 400 to 1.26 MPa, and 20 to 150 kPa, respectively. Densification also increased construct resistance to collagenase degradability. Finally, this process was amenable to creating high-density cellularized tissues; all constructs maintained high cell viability (at least 97%) immediately following compression as well as after 1 day and 7 days of culture. This method, which integrates the suprafibrillar assembly capacity of oligomers and controlled fluid reduction by confined compression, supports the rational and scalable design of a broad range of collagen-fibril materials and cell-encapsulated tissue constructs for tissue engineering applications.

Murine ultrasound-guided transabdominal para-aortic injections of self-assembling type I collagen oligomers

“…However, commercial grade monomeric collagen sources have slow polymerization rates and produce gels or matrices with low mechanical integrity, thus limiting their use as an injectable therapeutic delivery vehicle in vivo (22). Recently, a new soluble type I collagen subdomain, termed oligomers, has been isolated from porcine dermis (23). Oligomers uniquely retain their natural intermolecular crosslinks, which induce suprafibrillar self-assembly to yield highly-branched collagen-fibril networks with improved mechanical integrity (23).…”

“…Recently, a new soluble type I collagen subdomain, termed oligomers, has been isolated from porcine dermis (23). Oligomers uniquely retain their natural intermolecular crosslinks, which induce suprafibrillar self-assembly to yield highly-branched collagen-fibril networks with improved mechanical integrity (23). Specifically, oligomer matrices prepared at 0.5-4 mg mL -1 exhibit shear storage modulus (G′) values of 40-1500 Pa compared to 2-300 Pa and 2-50 Pa for telocollagen and atelocollagen respectively (22).…”

Use of autologous adipose‐derived mesenchymal stem cells for creation of laryngeal cartilage

“…In the current study, we explore the use of a patented oligomeric collagen, which uniquely retains natural collagen intermolecular cross‐links. This model supports suprafibrillar assembly to yield a highly interconnected D‐banded collagen–fibril network that is more mechanically stable and resistant to proteolytic degradation compared to those formed by conventional monomeric collagens . The oligomer collagen scaffold is in the form of a solution that rapidly self‐assembles into a solid contiguous regeneration matrix when activated.…”

“…The aim of this study was to determine if a unique oligomeric collagen could be combined with adipose‐derived stem cells (ASCs) to create three‐dimensional laryngeal cartilage. We hypothesized that the cartilage grafts created from ASCs in collagen could be used to consistently repair partial laryngeal defects in a rat model.…”

“…This model supports suprafibrillar assembly to yield a highly interconnected D-banded collagen-fibril network that is more mechanically stable and resistant to proteolytic degradation compared to those formed by conventional monomeric collagens. [9][10][11][12] The oligomer collagen scaffold is in the form of a solution that rapidly selfassembles into a solid contiguous regeneration matrix when activated. The methodology allows stem cells and collagen oligomers to be suspended in solution prior to polymerization into a solid state, and has been shown to promote rapid vascularization in vivo.…”