Effect of poly(ethylene glycol) diacrylate concentration on network properties and in vivo response of poly(β‐amino ester) networks

Abstract

Poly(β-amino ester) networks have shown promise as tissue scaffolds. The objective of this work was to examine the effect of changing poly(ethylene glycol) diacrylate concentration on poly(β-amino ester) network properties and to assess the degradable polymers' in vivo response, using magnetic resonance imaging (MRI) and immunohistochemistry. The networks were synthesized from hexanediol diacrylate (HDDA), poly(ethylene glycol) diacrylate (PEGDA), and a primary amine, 3-methoxypropylamine (3-MOPA), with a fixed overall molar ratio of diacrylate to amine. Network properties were verified to insure that the networks possessed equivalent initial properties and structure other than chemistry. The effect of varying PEGDA concentration on water content, mass loss, and modulus was determined, where increasing the concentration of PEGDA increases both water content, mass loss rate, and decreases modulus. We also show that manipulating the network composition at ratios of 0:100, 10:90 and 25:75 (PEGDA:HDDA) does not elicit a major inflammatory response to subcutaneous implantation of the networks in mice. This work provides a foundation for tailoring poly(β-amino ester) networks, based on degradation rate and modulus, as a means to tune the polymer properties for various biomedical applications.

Temporal and spatial distribution of macrophage phenotype markers in the foreign body response to glutaraldehyde-crosslinked gelatin hydrogels

“…Moreover, Safranski et al . showed that degradation rate of PEG-based hydrogels did not affect the thickness of the fibrous capsule or staining intensity for iNOS or Arg1 after 8 weeks of subcutaneous implantation in mice [28], in agreement with our results. Although these studies are not exhaustive, separate groups have now reported the counterintuitive finding that degradation rate does not have a significant effect on macrophage phenotype or on the FBR to crosslinked hydrogels made from both synthetic and natural polymers.…”

“…One study showed that a decrease in poly(ethylene glycol) (PEG)-based hydrogel stiffness (and increase in swelling ratio) resulted in a decrease in the thickness of the fibrous capsule following implantation in C57BL/6 mice for 28 days, concomitant with a decrease in inflammatory (i.e., M1) gene expression by macrophages [27]. In contrast, another study found that different degradation profiles, and therefore different elastic modulus profiles, of PEG-based hydrogels did not affect macrophage phenotype or the FBR in a similar mouse model [28]. …”

Semi-degradable poly(β-amino ester) networks with temporally controlled enhancement of mechanical properties

“…This diacrylate mixture was combined with 3MOPA at a molar ratio at 1.15:1 to ensure acrylate endgroups. The step-growth polymerization to form degradable PBAE macromers occurred for 24 hours at 200 rpm at 90°C on a JKEM reaction block (RBC-20 with BTS-1500 shaker) following [31,33]. The resulting macromers were verified by 1 H NMR on a Varian Mercury Vx 400 in deuterated chloroform and chemical structure can be found in [33], where the PEGDA units are incorporated between HDDA units of the macromer.…”

“…The influence of environment was also examined, where samples were tested in vitro and in vivo to verify that this effect was not limited to an in vitro setting. Three biodegradable crosslinkers, poly(β-amino ester)s with acrylate endgroups, were synthesized with varying levels of hydrophilicity to alter mass loss rate [31, 33]. By combining them with a nondegradable, high Tg monomer, such as methyl methacrylate, the Tg of the network was increased to ambient conditions [32].…”

“…By combining them with a nondegradable, high Tg monomer, such as methyl methacrylate, the Tg of the network was increased to ambient conditions [32]. The biodegradable crosslinkers have shown previous biocompatibility in vivo , and PMMA is well known to be biocompatible [33–35]. In order for the PBAE-MMA network to have the same benefits of standard biodegradable polymers, it must elicit a favorable biological response, while also showing an increase in modulus during degradation.…”