Shear-resistant hydrogels to control permeability of porous tubular scaffolds in vascular tissue engineering.

Aiming to perfuse porous tubular scaffolds for vascular tissue engineering (VTE) with controlled flow rate, prevention of leakage through the scaffold lumen is required. A gel coating made of 8% w/v alginate and 6% w/v gelatin functionalized with fibronectin was produced using a custom-made bioreactor-based method. Different volumetric proportions of alginate and gelatin were tested (50/50, 70/30, and 90/10). Gel swelling and stability, and rheological, and uniaxial tensile tests reveal superior resistance to the aggressive biochemical microenvironment, and their ability to withstand physiological deformations (~10%) and wall shear stresses (5-20 dyne/cm2). These are prerequisites to maintain the physiologic phenotypes of vascular smooth muscle cells and endothelial cells (ECs), mimicking blood vessels microenvironment. Gels can induce ECs proliferation and colonization, especially in the presence of fibronectin and higher percentages of gelatin. The custom-designed bioreactor enables the development of reproducible and homogeneous tubular gel coating. The permeability tests show the effectiveness of tubular scaffolds coated with 70/30 alginate/gelatin gel to occlude wadding pores, and therefore prevent leakages. The synthesized double-layered tubular scaffolds coated with alginate/gelatin gel and fibronectin represent both promising substrate for ECs and effective leakproof scaffolds, when subjected to pulsatile perfusion, for VTE applications.

The Crosstalk between Tissue Engineering and Pharmaceutical Biotechnology: Recent Advances and Future Directions.

Tissue-engineered constructs made of biotechnology-derived materials have been preferred due to their chemical and physical composition, which offers both high versatility and a support to enclose/ incorporate relevant signaling molecules and/or genes known to therapeutically induce tissue repair. Herein, a critical overview of the impact of different biotechnology-derived materials, scaffolds, and recombinant signaling molecules over the behavior of cells, another element of tissue engineered constructs, as well its regulatory role in tissue regeneration and disease progression is given. Additionally, these tissue-engineered constructs evolved to three-dimensional (3D) tissue-like models that, as an advancement of two-dimensional standard culture methods, are expected to be a valuable tool in the field of drug discovery and pharmaceutical research. Despite the improved design and conception of current proposed 3D tissue-like models, advanced control systems to enable and accelerate streamlining and automation of the numerous labor-intensive steps intrinsic to the development of tissue-engineered constructs are still to be achieved. In this sense, this review intends to present the biotechnology- derived materials that are being explored in the field of tissue engineering to generate 3D tissue-analogues and briefly highlight their foremost breakthroughs in tissue regeneration and drug discovery. It also aims to reinforce that the crosstalk between tissue engineering and pharmaceutical biotechnology has been fostering the outcomes of tissue engineering approaches through the use of biotechnology-derived signaling molecules. Gene delivery/therapy is also discussed as a forefront area that represents another cross point between tissue engineering and pharmaceutical biotechnology, in which nucleic acids can be considered a "super pharmaceutical" to drive biological responses, including tissue regeneration.

Development of an injectable PHBV microparticles-GG hydrogel hybrid system for regenerative medicine.

Uncontrollable displacements that greatly affect the concentration of active agents at the target tissues are among a major limitation of the use of microparticulate drug delivery systems (DDS). Under this context a biphasic injectable DDS combining poly(hydroxybutyrate-co-hydroxyvalerate) (PHBV) microparticles (MPs) and a gellan gum (GG) injectable hydrogel is herein proposed for the localized delivery and long-term retention of MPs carrying hydrophilic and hydrophobic model active agents. A double emulsion-solvent evaporation method was adopted to develop the PHBV MPs, carrying bovine serum albumin (BSA) or dexamethasone (Dex) as hydrophilic and hydrophobic active agents' models, respectively. Moreover, this method was modified, together with the properties of the hydrogel to tailor the delivery profile of the active agents. Variations of the composition of the organic phase during the process allowed tuning surface topography, particle size distribution and core porosity of the PHBV MPs and, thus, the in vitro release profile of Dex but not of BSA. Besides, after embedding hydrogels of higher GG concentration led to a slower and more sustained release of both active agents, independently of the processing conditions of the microparticulate system.