Superior Tissue Evolution in Slow-Degrading Scaffolds for Valvular Tissue Engineering

Abstract

Synthetic polymers are widely used to fabricate porous scaffolds for the regeneration of cardiovascular tissues. To ensure mechanical integrity, a balance between the rate of scaffold absorption and tissue formation is of high importance. A higher rate of tissue formation is expected in fast-degrading materials than in slow-degrading materials. This could be a result of synthetic cells, which aim to compensate for the fast loss of mechanical integrity of the scaffold by deposition of collagen fibers. Here, we studied the effect of fast-degrading polyglycolic acid scaffolds coated with poly-4-hydroxybutyrate (PGA-P4HB) and slow-degrading poly-ɛ-caprolactone (PCL) scaffolds on amount of tissue, composition, and mechanical characteristics in time, and compared these engineered values with values for native human heart valves. Electrospun PGA-P4HB and PCL scaffolds were either kept unseeded in culture or were seeded with human vascular-derived cells. Tissue formation, extracellular matrix (ECM) composition, remaining scaffold weight, tissue-to-scaffold weight ratio, and mechanical properties were analyzed every week up to 6 weeks. Mass of unseeded PCL scaffolds remained stable during culture, whereas PGA-P4HB scaffolds degraded rapidly. When seeded with cells, both scaffold types demonstrated increasing amounts of tissue with time, which was more pronounced for PGA-P4HB-based tissues during the first 2 weeks; however, PCL-based tissues resulted in the highest amount of tissue after 6 weeks. This study is the first to provide insight into the tissue-to-scaffold weight ratio, therewith allowing for a fair comparison between engineered tissues cultured on scaffolds as well as between native heart valve tissues. Although the absolute amount of ECM components differed between the engineered tissues, the ratio between ECM components was similar after 6 weeks. PCL-based tissues maintained their shape, whereas the PGA-P4HB-based tissues deformed during culture. After 6 weeks, PCL-based engineered tissues showed amounts of cells and ECM that were comparable to the number of human native heart valve leaflets, whereas values were lower in the PGA-P4HB-based tissues. Although increasing in time, the number of collagen crosslinks were below native values in all engineered tissues. In conclusion, this study indicates that slow-degrading scaffold materials are favored over fast-degrading materials to create organized ECM-rich tissues in vitro, which keep their three-dimensional structure before implantation.

In Vitro Hydrodynamic Evaluation of a Scaffold for Heart Valve Tissue Engineering

“…However, due to their stiffness, they were not considered completely suitable for a heart valve scaffold, and several other alternatives have been tested ever since to overcome this limitation, including PCL . Also, a recent publication by Brugmans et al indicated that slow‐degrading scaffolds (such as those made of PCL) show a superior tissue evolution when compared to fast‐degrading materials (like PGA), keeping their structural integrity and shape over time .…”

Biodegradable Poly-ε-Caprolactone Scaffolds with ECFCs and iMSCs for Tissue-Engineered Heart Valves

“…Poly-ε-caprolactone is one of the favored synthetic biomaterials as it combines many desirable properties such as biocompatibility, biodegradability, mechanical strength and flexibility [ 17 ]. Its biocompatibility and strength with good results in cell infiltration [ 19 , 32 ] makes it particularly interesting for the production of implantable long-term prostheses. PCL has already been approved by the Food and Drug Administration (FDA) for specific uses in the human body [ 33 ].…”

Blending Polymer Labile Elements at Differing Scales to Affect Degradation Profiles in Heart Valve Scaffolds

“…Reimer et al 46 performed fatigue testing under pulsatile conditions on decellularized tissue valves obtained from ovine dermal fibroblasts, but did not specifically evaluate scaffold degradation nor were the effects of enzymes considered. Sant et al 57 as well as Brugmans et al 58 evaluated in a pulse duplicator the degradation of heart valve leaflet made of fastdegrading polyglycolic acid scaffolds coated with poly-4hydroxybutyrate and slow-degrading poly-ε-caprolactone. Yet, the evaluation was not based on a fully assembled valve.…”