In Vivo Evaluation of the Regenerative Capability of Glycylglycine Ethyl Ester-Substituted Polyphosphazene and Poly(lactic-co-glycolic acid) Blends: A Rabbit Critical-Sized Bone Defect Model

Abstract

In an effort to understand the biological capability of polyphosphazene-based polymers, three-dimensional biomimetic bone scaffolds were fabricated using the blends of poly­[(glycine ethylglycinato)75(phenylphenoxy)25]­phosphazene (PNGEGPhPh) and poly­(lactic-co-glycolic acid) (PLGA), and an in vivo evaluation was performed in a rabbit critical-sized bone defect model. The matrices constructed from PNGEGPhPh–PLGA blends were surgically implanted into 15 mm critical-sized radial defects of the rabbits as structural templates for bone tissue regeneration. PLGA, which is the most commonly used synthetic bone graft substitute, was used as a control in this study. Radiological and histological analyses demonstrated that PNGEGPhPh–PLGA blends exhibited favorable in vivo biocompatibility and osteoconductivity, as the newly designed matrices allowed new bone formation to occur without adverse immunoreactions. The X-ray images of the blends showed higher levels of radiodensity than that of the pristine PLGA, indicating higher rates of new bone formation and regeneration. Micro-computed tomography quantification revealed that new bone volume fractions were significantly higher for the PNGEGPhPh–PLGA blends than for the PLGA controls after 4 weeks. The new bone volume increased linearly with increasing time points, with the new tissues observed throughout the defect area for the blend and only at the implant site’s extremes for the PLGA control. Histologically, the polyphosphazene system appeared to show tissue responses and bone ingrowths superior to PLGA. By the end of the study, the defects with PNGEGPhPh–PLGA scaffolds exhibited evidence of effective bone tissue ingrowth and minimal inflammatory responses. Thus, polyphosphazene-containing biomaterials have excellent translational potential for use in bone regenerative engineering applications.

Biocompatible Synthetic Polymers for Tissue Engineering Purposes

“…Block copolymers ,, usually with an ABA-structure (hard A blocks and a soft B portion), are good options because hard blocks provide mechanical strength and soft blocks enhance the hydrophilicity of the scaffold, promoting cell attachment. The polymers used most often recently in bone TE are PCL, ,,,− PLGA, ,,,,,, PUs, , followed by PLGA- b -PEG- b -PLGA, polymethacrylate derivatives, poly­(propylene fumarate), polyphosphazenes, polyhydroxyalkanoates, and combinations thereof.…”

Cyclo- and Polyphosphazenes for Biomedical Applications

“…Also in vivo, tests have been carried out by using glycylglycine ethyl-ester-substituted polyphosphazene and poly(lactic-co-glycolic acid)blends in a rabbit critical-sized bone defect model. Based on radiological and histological analyses, bone regeneration and a mild inflammatory response were observed, proving these materials to be viable for matrix-based bone regenerative engineering [ 225 ].…”

Development of porcine skeletal muscle extracellular matrix–derived hydrogels with improved properties and low immunogenicity

“…This knowledge plays a pivotal role in regenerative engineering, where the objective is often to emulate the native ECM’s composition, structure, and mechanical properties in the scaffold design to facilitate the regeneration of damaged tissues or organs ( 6 – 15 ). Currently, various natural and synthetic scaffold materials have been developed using the biochemical, mechanical, and structural cues from the native ECM as a blueprint ( 16 , 17 ).…”