Synthetic Tissue Scaffolds

Radical cystectomy accounts for the highest percentage of bladder related surgeries in the world today. The current standard surgical treatment for such a procedure is creating an ileal diversion. In this procedure, the bladder is removed, and the urine is allowed to drain freely into part of the ileum (the last segment of the small intestine). The end of the ileum is then brought out through an opening in the abdominal wall where a bag gathers the urine (Urinary Reconstruction and Diversion n.d.). However, such a diversion is associated with various complications such as ionic and osmotic disturbances, vitamin deficiencies, and bone mineral loss (Tomasz, Adamowicz, Sharma 2012, 561). Ex vivo regeneration and subsequent transplantation of a new bladder has demonstrated considerable success in providing patients with urinary reservoir. Urothelial and muscle cells harvested from a patient’s bladder are cultured on a growth medium for several weeks before being added to a three dimensional bladder shaped scaffold. Such a structure is designed to degrade in the body, making the Ex vivo cultured bladder a natural part of the body (Tissue Engineering: Partial Bladder Replacement n.d.).

Thus, the scaffold used to create an engineered bladder must firstly be biocompatible. It must also be able to support the adhesion and proliferation of urothelial cells on the luminal side and smooth muscle cells surrounding the urothelial barrier. In addition, it is essential that it have high porosity and surface area for cell migration and nutrient perfusion. Moreover, it must have the mechanical strength to resist damage through in vivo forces such as pressure from the urine and the muscles surrounding the bladder. Lastly, it needs to be ductile enough to be moulded into a bladder like shape. Today, various naturally derived materials are used for bladder scaffolds such as Alginate and Collagen.

Collagen is one of the most abundant proteins found in animal and plant tissue. The presence of collagen in the extra cellular matrix (ECM) of cells makes it is highly biocompatible and biodegradable. Collagen molecules are comprised of three α chains that assemble due to their molecular structure. Acellular ECM is typically used from human or porcine dermis or from swine intestine or bladder sub mucosa for the urothelial scaffold. To make a collagen scaffold, all materials in the final scaffold should be mixed together to form an aqueous solution. This solution has to be centrifuged, vacuumed, and placed in a mould, which is then frozen. Afterwards, the samples have to be freeze dried or lyophilized and then pushed out of their moulds (Al-Munajjed, Plunkett, Gleeson, Weber, Jungreuthmayer n.d.) Collagen is a highly porous and permeable material. Its Young’s modulus (30–80 kPa) and strength at 20% strain (2–8 kPa) is higher than gelatine samples (E = 2–6 kPa and σ = 0.4–0.7 kPa) (Grover, Best, Cameron n.d.). Thus, it has a high mechanical strength that can resist breakage once placed inside the body. However, collagen also possesses certain acute disadvantages such as the potential to cause alteration of cell behaviour (changes in growth or movement) once inside the body. In addition, because cells interact so easily with collagen, they actually break the alpha chains of the material causing the scaffold to lose its shape. In a cellular environment, collagen scaffolds display uncontrollable mechanical properties such as contractions or shrinkage (UWEB :: Research: Biomaterials Tutorial n.d.). Thus, collagen scaffolds are unreliable for bladder replacements unless they are cross-linked with other proteins that stabilize their mechanical properties. Alginate is a polysaccharide isolated from Phaeophyceae (brown seaweed). To begin, the extract is treated with aqueous alkali solutions such as NaOH this extract is then filtered and Sodium or calcium chloride is added to precipitate alginate. Treatment of alginate with dilute Hydrochloric Acid (HCl) makes alginic acid Further purification of the acid produces water-soluble sodium alginate powder. Alginate is biocompatible for it retains the structure of the Extra Cellular Matrix of the human body. It has extremely low toxicity and relatively cheap cost. It also forms gel like properties, which aid in easy moulding, when covalently cross-linked with Cations. Its controllable porosity aids in cell-cell interactions. Structurally, Alginates are linear (un branched) chains of monosaccharide. They belong to a family of copolymers of beta D Mannuronate (M block) and alpha L-guluronate (G block) (Peter, Jennifer 2005). Only G blocks, however, participate in the intermolecular cross-linking with Cations such as Ca2+ that increase the elasticity and gel like properties of the substance (Lee, Mooney 2012, 106). Thus, if a certain type of Alginate contains many G blocks, the Alginate will tend to have a high viscosity and a high elastic modulus (average elastic modulus = 3KPa), providing mechanical strength able to withstand in vivo forces. Still, the modulus is lower than Collagen’s elastic modulus (average = 5KPa). In addition, Alginate has extremely low cell adhesion. High contents of the G block stimulate cytokine (signalling proteins) production by white blood cells, which can cause inflammation and the breakdown of the scaffold. The gelation rate of alginate is hard to control for it varies with varying temperature. Often, the resulting structure is not uniform, and thus cannot act as a reliable scaffold. Alginate needs proteins such as collagen to increase its adhesion and mechanical strength (Andersen, Bent L., KjetiI, Eben, and Bjørn E. 2012, 227).

In addition to naturally derived polymers, synthetic polymers are highly elusive to tissue engineers for their physical and chemical structure can be easily controlled for desired mechanical and chemical properties. For example, poly(lactic-co-glycolic) or PLGA’s yielding stress can easily be increased through increased porosity, which in turn can be achieved through methods such as soaking the scaffold in sodium hydroxide solution (Pattison, Wurster, Webster, Haberstroh 2005, 2491). Synthetic scaffolds can be effortlessly processed, and their properties remain relatively constant over time. One of the major hurdles of synthetic polymers is biocompatibility. Solutions such as coating the plastic polymer with cells from the body have recently surfaced in the world of tissue engineering. To conclude, alginate and collagen are two of the many substances used in designing scaffolds for the urothelial and muscle cells of the bladder. Their combination with synthetic polymers holds the future of scaffolding.