Porous Structures: In situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide‐Based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering (Adv. Funct. Mater. 17/2010)

Abstract

Synthetic biodegradable polymers serve as temporary substrates that accommodate cell infiltration and tissue in-growth in regenerative medicine. To allow tissue in-growth and nutrient transport, traditional three-dimensional (3D) scaffolds must be prefabricated with an interconnected porous structure. Here we demonstrated for the first time a unique polymer erosion process through which polymer matrices evolve from a solid coherent film to an assemblage of microspheres with an interconnected 3D porous structure. This polymer system was developed on the highly versatile platform of polyphosphazene-polyester blends. Co-substituting a polyphosphazene backbone with both hydrophilic glycylglycine dipeptide and hydrophobic 4-phenylphenoxy group generated a polymer with strong hydrogen bonding capacity. Rapid hydrolysis of the polyester component permitted the formation of 3D void space filled with self-assembled polyphosphazene spheres. Characterization of such self-assembled porous structures revealed macropores (10-100 μm) between spheres as well as micro- and nanopores on the sphere surface. A similar degradation pattern was confirmed in vivo using a rat subcutaneous implantation model. 12 weeks of implantation resulted in an interconnected porous structure with 82-87% porosity. Cell infiltration and collagen tissue in-growth between microspheres observed by histology confirmed the formation of an in situ 3D interconnected porous structure. It was determined that the in situ porous structure resulted from unique hydrogen bonding in the blend promoting a three-stage degradation mechanism. The robust tissue in-growth of this dynamic pore forming scaffold attests to the utility of this system as a new strategy in regenerative medicine for developing solid matrices that balance degradation with tissue formation.

Biodegradable Polyphosphazene-Based Blends for Regenerative Engineering

“…Numerous biodegradable polyphosphazenes have been synthesized by substitution of chlorine atoms of the poly(dichlorophospazene) with hydrolytically labile groups such as amino acid esters, glycolate or lactate ester, imidazole, steroidal residue, and glyceryl[5, 9, 10, 12, 31, 32, 39, 45-47, 61, 63, 65, 66, 70, 71, 74-77]. Table 1 summarizes the physiochemical properties of some of the representative polyphosphazenes used in biomedical applications[5-7, 9, 10, 15, 22, 26-28, 32, 33, 37, 39, 46, 49, 51, 65, 76, 78-84]. Bulkier side groups result in a higher T g [10, 27, 35, 37, 46, 61, 78, 79].…”

“…Deng et al [51] carried out a study on the degradation of PPHOS-PLAGA in PBS. In that study, the self-neutralizing ability of the blend system was examined by monitoring the pH profile of degradation in PBS.…”

“…A 12-week of in vitro degradation led to 70-80% mass loss. [18, 23, 29, 41, 51, 71, 91, 93-95]. Furthermore, by appropriately changing the polymer chemistry and adjusting the composition of the blends, the buffering capacity and the resulting pH environment can be well tuned.…”

“…It has been found that the size of the microspheres formed as well as the pore diameter can be varied by varying the blend composition. These unique in situ created porous structures, which are structurally similar to sintered microsphere matrix, have significant potential for cell in-growth and tissue regeneration [18, 51]. …”

“…Despite polyphosphazenes having unique tunability through their side group chemistry, occasionally this is not enough to meet properties requirements for specific biomedical applications and thus polyphosphazene-based blends have also been explored as potential biomaterials [12, 14, 15, 18, 19, 22, 23, 26, 28, 30, 37, 39, 41, 43, 48, 51]. Blending technique is a very cost effective way of producing new polymeric materials with unique properties and without having to go through the rigorous synthetic protocol.…”