Ex situ bioengineering of bioartificial endocrine glands: A new frontier in regenerative medicine of soft tissue organs

A combined additive layer manufacturing / indirect replication method to prototype 3D vascular-like structures of soft tissue and endocrine organs

“…In particular, we choose to reconstruct 9 Virtual and Physical Prototyping the intraparenchymal distribution of the arteries of the human thyroid gland and kidney. To get a digital representation of these vascular architectures, we have used a recently developed algorithm capable of modelling the intraparenchymal vascular distribution of soft viscera within their geometrical domain (Spaletta 2004, Della Casa et al 2006, Toni et al 2011. The ensuing computational model adopts the idea that these vascular organisations can be represented via fractal geometry.…”

“…This network has been recently shown to be a key geometrical regulator for growth of seeded cells during ex situ bioengineering procedures aimed at reconstructing entire viable organs for transplantation (Toni et al 2011). In particular, we choose to reconstruct 9 Virtual and Physical Prototyping the intraparenchymal distribution of the arteries of the human thyroid gland and kidney.…”

“…The simulated SVS grew inside the geometrical limits (volume and shape) of the reconstructed thyroid lobe; as a result, it yielded a model of the normal arterial vascularisation inside the volume of an adult thyroid lobe. Growth of vascular arborisations was restricted to a binary model of second and third order intraglandular arteries, whereas position and number of second order branches on the contour of the lobe were arbitrarily fixed and limited to 4 to 8 vessels for each surface side (Della Casa et al 2006, Toni et al 2011). A simplified model was also produced, where a portion of the arterial structure was obtained by the growth of a branch from a single seed.…”

“…Similarly, we have collected evidence that also ex situ selfassembly of the human thyroid parenchyma can be regulated by the geometrical properties of a biocompatible physical support mimicking its natural SVS (Toni et al 2007(Toni et al , 2008. Therefore, we decided to develop a flexible and powerful STL-based computational algorithm to reconstruct the 3D architecture of human soft tissue and endocrine organs within their volumetric domain, and in preliminary studies we successfully applied it to the simulation of the thyroid SVS (Toni et al 2011). Encouraged by these achievements, we have started to investigate the capability of this algorithm to drive the rapid prototyping of intrathyroidal arterial branches with different materials (including biomaterials), and using different Additive Layer Manufacturing (ALM) techniques (Bassoli et al 2011).…”

“…Since experimental evidence has shown that the three-dimensional (3D) geometry of the environment regulates the growth of seeded cells (Ingber 2005, Vogel andSheetz 2006), we have recently explored the possibility of guiding the ex situ self-assembly of glandular / parenchymal tissue using a 3D biocompatible scaffold that mimics the macro-microscopic geometry of the natural stromal / vascular scaffold (SVS) of the native organ, i.e. an organomorphic scaffold (Toni et al 2011). In particular, we have chosen as a reconstruction model the thyroid gland, due to its simple anatomical organisation, with the intent to eventually extend our bioengineering procedure to the reconstruction of other endocrine and soft tissue viscera.…”