(599g) Modification Of A Naturally Derived Matrix Using Nanoparticles

Porcine small intestinal submucosa (SIS) has been intensively studied in regenerating various organs. It has also been used clinically for bladder reconstruction. The major advantage of using SIS in bladder augmentation is that, unlike other synthetic biomaterials, SIS does not require prior cell seeding for the regeneration process. This may result from the fact that the SIS possesses growth factors and physical properties for surrounding cell to migrate into the biomaterial.

While the majority of augmentations were successful in animal models, results were inconsistent in a number of experiments. The inconsistency is likely attributed to SIS permeability to urea. Urea leaking from the bladder can cause inflammation and lead to inconsistent wound healing. Because SIS is a naturally derived matrix its properties are heterogeneous. The permeability of SIS varies animal to animal, by animal age, and is location dependent. SIS harvested close to the pancreas (proximal) has different physical properties from SIS harvested further away (distal) [1]. To decrease heterogeneity of SIS, one approach considered in this study was to incorporate nanoparticles which could also be used for local delivery of essential growth factors.

First, 50 nm to 1000 nm size latex spheres were utilized to determine an optimum particle size that could effectively alter the permeability of SIS. For this purpose, they were incorporated into SIS by gravity settling (as assessed by scanning electron microscopy) and permeability to urea was measured. These results showed suitability of 200 nm and 500 nm particles. Next, biodegradable poly (DL-lactide-co-glycolide) (PLGA) nanoparticles (NPs), 260 nm in diameter and a polydispersity of 0.150, were synthesized using a double-emulsion method [2]. Different concentrations of 260 nm PLGA NPs (0.1, 1 and 5 mg/mL) were placed on SIS, similar to latex particles. Measured permeability showed reduction in permeability and 1 mg/mL particle concentration to be optimum. To understand the effect of immobilizing nanoparticles on mechanical characteristics, tensile properties were measured at physiological conditions [1] The addition of PLGA NPs onto the SIS did not alter tensile properties of SIS. Further, cellular activity of endothelial cells was tested up to fourteen days which showed no change in cell morphology and no reduction in cell colonization ability. In summary, the inclusion of PLGA NPs reduces the SIS permeability to urea and shows a promising potential to improve the efficiency of tissue regenerating process.

[1] Raghavan D, Kropp BP, Lin H-K, Zhang Y, Cowan R, Madihally SV. Physical Characteristics of Small Intestinal Submucosa Scaffolds are Location-Dependent. Journal of Biomedical Materials Research-Part A. 2005;73A: 90?96.

[2] Astete CE, Sabliov CM. Synthesis and characterization of PLGA nanoparticles. Journal of Biomaterials Science-Polymer Edition. 2006;17: 247-289.