Tunability of collagen matrix mechanical properties via multiple modes of mineralization

Abstract

Functionally graded, mineralized collagen tissues exist at soft-to-hard material attachments throughout the body. However, the details of how collagen and hydroxyapatite mineral (HA) interact are not fully understood, hampering efforts to develop tissue-engineered constructs that can assist with repair of injuries at the attachments of soft tissues to bone. In this study, spatial control of mineralization was achieved in collagen matrices using simulated body fluids (SBFs). Based upon previous observations of poor bonding between reconstituted collagen and HA deposited using SBF, we hypothesized that mineralizing collagen in the presence of fetuin (which inhibits surface mineralization) would lead to more mineral deposition within the scaffold and therefore a greater increase in stiffness and toughness compared with collagen mineralized without fetuin. We tested this hypothesis through integrated synthesis, mechanical testing and modelling of graded, mineralized reconstituted collagen constructs. Results supported the hypothesis, and further suggested that mineralization on the interior of reconstituted collagen constructs, as promoted by fetuin, led to superior bonding between HA and collagen. The results provide us guidance for the development of mineralized collagen scaffolds, with implications for bone and tendon-to-bone tissue engineering.

Strain Distribution of Intact Rat Rotator Cuff Tendon-to-Bone Attachments and Attachments With Defects

“…At the macroscale, the tendon-to-bone attachment splays outwardly, increasing its cross-sectional area (CSA) from tendon to bone to reduce localized stress at the interface [8,9]. At the microscale, a gradient of unmineralized and mineralized fibrocartilage [6,10,11], as well as collagen fibril interdigitations and alignment, aid in reducing or redirecting localized stress [4,9,[11][12][13][14][15]. At the nanoscale, pattern variations in mineral accumulation around collagen fibers and within the collagen molecular structure may also modulate macroscale attachment biomechanics [4].…”

Modifying the strength and strain concentration profile within collagen scaffolds using customizable arrays of poly-lactic acid fibers

“…Emerging efforts have begun to shift focus from homogenous biomaterials for the purpose of regenerating a single tissue (Caliari et al, 2011; Ferreira et al, 2012; Galatz et al, 2006; Kanungo et al, 2008; Levingstone et al, 2014; Mathew et al, 2012) to multi-compartment and spatially graded biomaterials for the express purpose of repairing more complex tissues such as the tendon-to-bone junction (Caliari et al, 2015a; Harley et al, 2010; Lipner et al, 2014; Qu et al, 2013; Smith et al, 2016; Weisgerber et al, 2015; Weisgerber et al, 2013b). Efforts in our lab have recently described two new variants of collagen scaffolds under development for osteotendinous repair applications.…”

Biomaterials to Mimic and Heal Connective Tissues

“…Strategies include using nanofibrous scaffolds with graded calcium phosphate [446] and collagen matrix submerged in simulated body fluid. [447] In another approach, a hierarchical scaffold was engineered with regions to guide cell ingrowth and collagen fiber alignment using interconnected gelatin beads infiltrated with hydroxyapatite and PLGA. [448] An array of channels was created to promote the formation of an aligned unmineralized scaffold prior to dissolving the gelatin to create a porous structure.…”