The Implications of Polymer Selection in Regenerative Medicine: A Comparison of Amorphous and Semi‐Crystalline Polymer for Tissue Regeneration

Abstract

Biodegradable polymeric scaffolds are being investigated as scaffolding materials for use in regenerative medicine. While the in vivo evaluation of various three‐dimensional (3D), porous, biodegradable polymeric scaffolds has been reported, most studies are ≤3 months in duration, which is typically prior to bulk polymer degradation, a critical event that may initiate an inflammatory response and inhibit tissue formation. Here, a 6 month in vitro degradation and corresponding in vivo studies that characterized scaffold changes during complete degradation of an amorphous, 3D poly(lactide‐co‐glycolide)(3D‐PLAGA) scaffold and near‐complete degradation of a semi‐crystalline3D‐PLAGA scaffold are reported. Using sintered microsphere matrix technology, constructs were fabricated in a tubular shape, with the longitudinal axis void and a median pore size that mimicked the architecture of native bone. Long‐term quantitative measurements of molecular weight, mechanical properties, and porosity provided a basis for theorization of the scaffold degradation process. Following implantation in a critical size ulnar defect model, histological analysis and quantitative microCT indicated early solubilization of the semi‐crystalline polymer created an acidic microenvironment that inhibited mineralized tissue formation. Thus, the use of amorphous over semi‐crystalline PLAGA materials is advocated for applications in regenerative medicine.

Dipeptide-based polyphosphazene and polyester blends for bone tissue engineering

“…This suggests that the phosphates and ammonia produced from the hydrolyzed polyphosphazene backbone were able to neutralize the acidic degradation of PLAGA and further reduce the auto-catalyzed PLAGA hydrolysis. The multiphase degradation profiles of blend matrices could be important in new bone regeneration, which involves sequential healing processes in the range of 12 to 24 weeks [31]. Furthermore, comparison of the degradation rate of the polymer matrices suggested that the order of degradation rate is PLAGA > Matrix1 > Matrix2.…”

Biomimetic Structures: Biological Implications of Dipeptide‐Substituted Polyphosphazene–Polyester Blend Nanofiber Matrices for Load‐Bearing Bone Regeneration

“…The regenerative effi cacy of utilizing a tubular matrix to heal a critical-sized ulna bone defect was recently demonstrated by our laboratory in a New Zealand White rabbit model. [ 44 ] Implantation of such tubular matrix resulted in a robust bone marrow stromal cell infi ltration to the scaffold interior as indicated by increased tissue volume. [ 44 ] Furthermore, the blend nanofi ber lamellar structures promote the osteoblast phenotype expression throughout the scaffold architecture, which would ultimately lead to the accelerated formation of mineralized tissues.…”

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

“…Such multi-phase degradation profi les of blend matrices would allow accommodating gradual tissue in-growth during the different stages of bone healing. [ 21 ] By 12 weeks, completely open 3D continuous architecture with macropores (10-100 μ m) between spheres in combination with micro/nanopores on the sphere surfaces formed with well packed polymer spheres ( Figure 2 g, h). This unique in situ created porous structure has signifi cant potential for cell in-growth and tissue regeneration.…”