Identification of osteoconductive and biodegradable polymers from a combinatorial polymer library

Abstract

Combinatorial polymer syntheses are now being utilized to create libraries of materials with potential utility for a wide variety of biomedical applications. We recently developed a library of photopolymerizable and biodegradable poly(β-amino ester)s (PBAEs) that possessed a range of tunable properties. In this work, the PBAE library was assessed for candidate materials that met design criteria (e.g., physical properties such as degradation and mechanical strength and in vitro cell viability and osteoconductive behavior) for scaffolding in mineralized tissue repair. The most promising candidate, A6, was then processed into 3-dimensional porous scaffolds and implanted subcutaneously and only presented a mild inflammatory response. The scaffolds were then implanted intramuscularly and into a critically-sized cranial defect either alone or loaded with bone morphogenetic protein-2 (BMP-2). The samples in both locations displayed mineralized tissue formation in the presence of BMP-2, as evident through radiographs, micro-computed tomography, and histology, while samples without BMP-2 showed minimal or no mineralized tissue. These results illustrate a process to identify a candidate scaffolding material from a combinatorial polymer library, and specifically for the identification of an osteoconductive scaffold with osteoinductive properties via the inclusion of a growth factor.

Jagged1 immobilization to an osteoconductive polymer activates the Notch signaling pathway and induces osteogenesis

“…Collectively, the data demonstrates the osteoinductive nature of Jagged1, where directly immobilized Jagged1/A6 moderately promotes cell proliferation and strongly induces osteoblast differentiation and calcified mineral deposition. The A6 polymer also demonstrated to be osteoconductive, confirming our previously established results …”

“…ORIGINAL ARTICLE JOURNAL OF BIOMEDICAL MATERIALS RESEARCH A | MAY 2014 VOL 102A, ISSUE 5 be osteoconductive, confirming our previously established results. 28…”

“…Then we evaluated the osteoinductive capacity of the Jagged1 biomaterial constructs using the ideal immobilization strategy. A novel poly(β‐amino ester) (PBAE) comprised of diethylene glycol diacrylate and isobutylamine, known as A6, was utilized as the biomaterial substrate, since previous studies have demonstrated its osteoconductive capability as a scaffold for protein delivery (BMP‐2) …”

“…A novel poly(b-amino ester) (PBAE) 27 comprised of diethylene glycol diacrylate and isobutylamine, known as A6, was utilized as the biomaterial substrate, since previous studies have demonstrated its osteoconductive capability as a scaffold for protein delivery (BMP-2). 28 This research aims to develop a clinically translatable therapy to improve bone regeneration by targeting the Notch signaling pathway. We hypothesize that delivery of Jagged1 bound to A6 [Jagged1=A6] will activate Notch signaling and induce osteoblast differentiation.…”

Synthesis and analysis of degradation, mechanical and toxicity properties of poly(β-amino ester) degradable hydrogels

“…The degradation and mechanical properties of these hydrogel systems have been analyzed [23] as well as their use as crosslinkers in other hydrogel networks [24]. Recent research has focused primarily on the use of poly(b-amino ester) biodegradable hydrogels as scaffolding materials [25][26][27] and drug delivery devices [3].…”