Endothelial Differentiation of Human Stem Cells Seeded onto Electrospun Polyhydroxybutyrate/Polyhydroxybutyrate-Co-Hydroxyvalerate Fiber Mesh

Tissue engineering is based on the association of cultured cells with structural matrices and the incorporation of signaling molecules for inducing tissue regeneration. Despite its enormous potential, tissue engineering faces a major challenge concerning the maintenance of cell viability after the implantation of the constructs. The lack of a functional vasculature within the implant compromises the delivery of nutrients to and removal of metabolites from the cells, which can lead to implant failure. In this sense, our investigation aims to develop a new strategy for enhancing vascularization in tissue engineering constructs. This study's aim was to establish a culture of human adipose tissue-derived stem cells (hASCs) to evaluate the biocompatibility of electrospun fiber mesh made of polyhydroxybutyrate (PHB) and its copolymer poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHB-HV) and to promote the differentiation of hASCs into the endothelial lineage. Fiber mesh was produced by blending 30% PHB with 70% PHB-HV and its physical characterization was conducted using scanning electron microscopy analysis (SEM). Using electrospinning, fiber mesh was obtained with diameters ranging 300 nm to 1.3 µm. To assess the biological performance, hASCs were extracted, cultured, characterized by flow cytometry, expanded and seeded onto electrospun PHB/PHB-HV fiber mesh. Various aspects of the cells were analyzed in vitro using SEM, MTT assay and Calcein-AM staining. The in vitro evaluation demonstrated good adhesion and a normal morphology of the hASCs. After 7, 14 and 21 days of seeding hASCs onto electrospun PHB/PHB-HV fiber mesh, the cells remained viable and proliferative. Moreover, when cultured with endothelial differentiation medium (i.e., medium containing VEGF and bFGF), the hASCs expressed endothelial markers such as VE-Cadherin and the vWF factor. Therefore, the electrospun PHB/PHB-HV fiber mesh appears to be a suitable material that can be used in combination with endothelial-differentiated cells to improve vascularization in engineered bone tissues

Tuning drug release in polyester thin films: terminal end-groups determine specific rates of additive-free controlled drug release

Modulating the drug release from polyester matrices independently of material properties would be beneficial to those designing biodegradable medical implants, such as drug delivery devices, stents and screws. However, the most common approaches use additives that often drastically alter the desired material properties. Recently, we have developed tools that allow gradient film formulations and high-throughput drug quantitation for the determination of parameter-specific correlations. We propose that modulated drug release can be obtained via additive-free mechanisms in polyesters by simply controlling polymer erosion through acidic terminal functional groups. Our results showed that drug release in poly(lactic-co-glycolic acid) (PLGA) formulations could be tuned to produce large ranges in drug release with relatively small changes in terminal acidic functional groups. For example, PLGA 53/47 thin films could be tuned to have 10–60% drug release at 14 days or 10–90% drug release at 20 days, depending on the PLGA/PLGA blend formulation and concentration of acidic terminal functional groups. A linear R-square correlation of up to 0.9 was observed for the acidic groups and percent drug release. Below a threshold of 1 part per thousand acidic groups, there was no increase in drug release, which has implications for polymer processing and film integrity.Published Versio