In situ Porous Structures: A Unique Polymer Erosion Mechanism in Biodegradable Dipeptide-Based Polyphosphazene and Polyester Blends Producing Matrices for Regenerative Engineering

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 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 is demonstrated for the first time. This polymer system is 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 generates a polymer with strong hydrogen bonding capacity. Rapid hydrolysis of the polyester component permits the formation of 3D void space filled with self-assembled polyphosphazene spheres. Characterization of such self-assembled porous structures reveals macropores (10-100 mu m) between spheres as well as micro-and nanopores on the sphere surface. A similar degradation pattern is confirmed in vivo using a rat subcutaneous implantation model. 12 weeks of implantation results in an interconnected porous structure with 82-87% porosity. Cell infiltration and collagen tissue ingrowth between microspheres observed by histology confirms the formation of an in situ 3D interconnected porous structure. It is determined that the in situ porous structure results 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.