Tuning scaffold mechanics by laminating native extracellular matrix membranes and effects on early cellular remodeling

Abstract

At approximately 50 μm thin, the human amniotic membrane (hAM) has been shown to be a versatile biomaterial with applications ranging from ocular transplants to skin and nerve regeneration. These investigations describe laminating layers of the hAM into a multilayered, conformation creating a thicker, more robust biomaterial for applications requiring more supportive structures. Amniotic membranes were decellularized using 4 M NaCl and prepared as either flat single-layered sheets or rolled into concentric five-layered configurations. Constructs were seeded with human vascular smooth muscle cells and cultured over 40 days to quantify biological and mechanical changes that occurred during early remodeling events. By day 40 single-layered constructs displayed a decreasing trend in cellular densities and glycosaminoglycan (GAG) concentration, comparative to multilayered constructs with increasing cell densities (from 9.1 to 32 × 106 cells/g) and GAG concentrations (from 6.07 to 17.4 mg/g). Oxygen diffusion was calculated and found to be sufficient to maintain cell populations through the constructs full thickness. Although an overall decrease in the modulus of elasticity was noted, the modulus in the failure range of rolled constructs stabilized at values 25 times higher than single-layered constructs. Rolled constructs typically displayed an upregulation of contractile and matrix remodeling markers (α-actin, SM22 and type 1 collagen, MMP-2 respectively) indicating biological adaptation. Considerable design flexibility can be achieved by varying the number of scaffold layers, allowing the possibility of tuning the constructs physical dimensions, shape and tensile properties to suit specific targeted vascular locations.

Influence of crosslinking on the mechanical behavior of 3D printed alginate scaffolds: Experimental and numerical approaches

“…As mentioned, the finite element model proposed only predicts the low-strain region of the stress-strain curve (linear elastic region). In some tissue engineering applications, such as nerve and skin regeneration, the linear, low-strain region of the stress-strain curve was used to calculate the elastic modulus of samples and considered to represent physiological behavior in the human vasculature (Amensag and McFetridge, 2014). In a similar study, isotropic linear elastic behavior was reported and 10% strain used to calculate the elastic modulus of scaffolds fabricated as cardiac-mimetic structures; furthermore, 10 to 25% strain was reported as the cardiac-relevant strain range in physiological conditions (Neal et al, 2012).…”

Combining NT3-overexpressing MSCs and PLGA microcarriers for brain tissue engineering: A potential tool for treatment of Parkinson's disease

“…Indeed, scaffolding materials may present a biomimetic structure of different extracellular matrix (ECM) components that could stimulate cell survival and differentiation [27,30]. It is however essential to optimize biological [31], mechanical [32,33] and physicochemical properties [34] of scaffolding material before they can be successfully employed. In brain tissue engineering, the size of the scaffold is one of the most crucial issues as it has to be small enough to be injectable into the site of lesion in deep brain [1,27].…”

Human Perinatal‐Derived Biomaterials

“…[34,48] Placental derived matrix has been shown to induce angiogenesis. [15] Bottom left represents capillaries formed in vitro on human placental matrix coated TC plate.…”