Mechanical Properties and Compositions of Tissue Engineered and Native Arteries

Abstract

With the goal of mimicking the mechanical properties of a given native tissue, tissue engineers seek to culture replacement tissues with compositions similar to those of native tissues. In this report, differences between the mechanical properties of engineered arteries and native arteries were correlated with differences in tissue composition. Engineered arteries failed to match the strengths or compliances of native tissues. Lower strengths of engineered arteries resulted partially from inferior organization of collagen, but not from differences in collagen density. Furthermore, ultimate strengths of engineered vessels were significantly reduced by the presence of residual polyglycolic acid polymer fragments, which caused stress concentrations in the vessel wall. Lower compliances of engineered vessels resulted from minimal smooth muscle cell contractility and a lack of organized extracellular elastin. Organization of elastin and collagen in engineered arteries may have been partially hindered by high concentrations of sulfated glycosaminoglycans. Tissue engineers should continue to regulate cell phenotype and promote synthesis of proteins that are known to dominate the mechanical properties of the associated native tissue. However, we should also be aware of the potential negative impacts of polymer fragments and glycosaminoglycans on the mechanical properties of engineered tissues.

Appendix

Calculation of Stress Concentrations Caused by Polymer Fragments

At the suture line, regions of densely packed PGA fragments (e.g., circled area in Fig. 4) were approximated as a single circular stress concentration in the vessel wall. The behavior of this stress concentration during mechanical testing was assumed to be analogous to a void within a plate being pulled in tension.3

To calculate the maximum local stress seen by engineered tissue bordering a polymer “void,” vessel wall thickness, h, and radius of the polymer void, r _void, were used to calculate the thickness of the vessel wall not containing polymer, d:

$$ d\,{\text{ = }}\,h\, - \,{\text{2}}r_{{\text{void}}} $$

(A1)

The ratio r _void/d was used to calculate a stress concentration factor, K _T, which ranged from 2.0 to 3.0:

$$ K_{\text{T}} \,{\text{ = }}\,\frac{{\sigma _{{\text{max}}} }} {{\sigma _{{\text{avg}}} }} $$

(A2)

where σ_max was the maximum stress seen by a tissue at a void edge, and σ_avg was the average stress across d (Fig. 5).

Figure 5.

Engineered vessels sense higher stresses near polymer fragments, which act as voids in the tissue, than at tissue sites far away from polymer fragments. σ_o was the stress seen across the vessel wall when stress distribution was not disrupted by polymer fragments. σ_avg was the average stress seen across d, the thickness of the vessel wall without the polymer particle. σ_max was the maximum stress seen by the tissue at the edge of the polymer or void space. P was the pressure exerted on the vessel lumen.

For a void space covering 15% of the vessel area, r _void/d = 0.118, and thus, K _T = 2.5.3 With

$$ \sigma _{\text{o}} \,{\text{ = }}\,\frac{{Pr_{\text{i}} }} {h}\,{\text{ = }}\,\frac{{{\text{Force}}}} {{{\text{SurfaceArea}}}} $$

(A3)

where r _i was the vessel inner radius, and

$$ \sigma _{{\text{avg}}} \,{\text{ = }}\,\frac{{{\text{Force}}}} {{{\text{(}}h\, - \,{\text{2}}r_{{\text{void}}} {\text{)}}\,\; \times \;\,{\text{length}}}}\,{\text{ = }}\,\frac{{{\text{SurfaceArea}}\, \times \,\sigma _{\text{o}} }} {{{\text{(}}h\, - \,{\text{2}}r_{{\text{void}}} {\text{)}}\,{\text{*}}\,{\text{length}}}} $$

(A4)

where length was the axial length of the tested vessel segment, σ_max could be calculated from Eq. (A2). The ratio σ_max/σ_o described the factor of increased stress seen by engineered tissue near the polymer void (Table 3). Thus, in the absence of polymer fragments at the suture line and elsewhere, engineered tissues may withstand pressures and stresses greater than 3 times their reported burst pressures and maximum stresses.