Promoted Osteoconduction of Polyurethane-Urea Based 3D Nanohybrid Scaffold through Nanohydroxyapatite Adorned Hierarchical Titanium Phosphate

ACS Appl Bio Mater. 2019 Sep 16;2(9):3907-3925. doi: 10.1021/acsabm.9b00487. Epub 2019 Aug 29.

Abstract

The lack of optimal physiological properties, bacterial colonization, and auto-osteoinduction, are the foremost issues of orthopedic implantations. In terms of bone healing, many researchers have reported the release of additional growth factors of the implanted biomaterials to accelerate the bone regeneration process. However, the additional growth factor may cause side effects such as contagion, nerve pain, and the formation of ectopic bone. Thus, the design of an osteoconductive scaffold having excellent biocompatibility, appropriate physicomechanical properties, and promoted auto osteoinductivity with antibacterial activity is greatly desired. In this study, 2D rodlike nanohydroxyapatite (nHA) adorned titanium phosphate (TP) with a flowerlike morphology was synthesized by a hydrothermal precipitation reaction. The nanohybrid material (nHA-TP) was incorporated into the synthesized polycaprolactone diol and spermine based thermoplastic polyurethane-urea (PUU) via in situ technique followed by salt leaching to fabricate the macroporous 3D polymer nanohybrid scaffold (PUU/nHA-TP). Structure explication of PUU was performed by NMR spectroscopy. The synthesized nanohybrid scaffold with 1% nHA-TP showed 67% increase of tensile strength and 18% improved modulus compared to the pristine PUU via formation of H-bonding or dative bonds between the metal and the amide linkage of the polyurethane or polyurea. In vitro study showing improved cell viability and proliferation of the seeded cell revealed the superior osteoconductivity of the nanohybrid scaffold. Most importantly, the in vivo experiments revealed a significant amount of bone regeneration in the nanohybrid scaffold implanted tibial site compared to the pristine scaffold without any toxic effect. Introduction of the minute amount of titanium phosphate within the adorned nHA promotes the osteoconductivity significantly by the capability of forming coordinate bonds of the titanium ion. Depending on the mechanical, physicochemical, in vitro characteristics, and in vivo osteoconductivity, the PUU/nHA-TP nanohybrid scaffold has great potential as an alternative biomaterial in bone tissue regeneration application.

Keywords: bone healing; hydroxyapatite; osteoconductive scaffold; physicomechanical properties; polyurethane−urea; titanium phosphate.