In vivo tissue responses to thermal-responsive shape memory polymer nanocomposites

Abstract

To explore the safe use of thermal-responsive shape memory polymers (SMPs) as minimally invasive tissue scaffolds, we recently developed a class of biodegradable POSS-SMP nanocomposites exhibiting stable temporary shape fixing and facile shape recovery within a narrow window of physiological temperatures. The materials were covalently crosslinked from star-branched building blocks consisting a bioinert polyhedral oligomeric silsesquioxane (POSS) core and 8 degradable poly(D,L-lactide) (PLA) arms. Here we examine the degradation profiles and immunogenicity of POSS-SMPs as a function of the PLA arm lengths using a rat subcutaneous implantation model. We show that POSS-SMPs elicited a mild foreign body type immune response upon implantation. The degradation rates of POSS-SMPs, both in vitro and in vivo, inversely correlated with the length of the PLA chains within the crosslinked amorphous network. Upon in vivo degradation of POSS-SMPs, a second acute inflammatory response was elicited locally, and the inflammation was able to resolve over time without medical interventions. One year after the implantation of POSS-SMPs, no pathologic abnormalities were detected from the vital/scavenger organs examined. These minimally immunogenic and biodegradable SMPs are promising candidates for scaffold-assisted tissue repair where both facile surgical delivery and controlled degradation of the scaffold are desired for achieving optimal short-term and long-term clinical outcomes.

Figure 1

Chemical composition and in vitro hydrolytic degradation of POSS-SMPs. (A) Star-branched macromer building blocks of POSS-SMP; (B) %Mass residue of POSS-SMPs as a function of PLA arm length upon incubation in PBS (pH 7.4) at 37 °C. A qualitative illustration of the tissue repair kinetics is shown in purple. A sample size of 3 was applied; (C) SEM micrographs of POSS-SMPs before and after 73-day incubation in PBS at 37 °C.

Figure 2

Foreign body type responses to (A) POSS-SMP-10 and (B) PLA control at 4, 18 and 60 days post subcutaneous implantation as revealed by H&E (cellularity) and Ki67 (proliferation) immunostaining. Center rows are higher resolution images of the areas boxed in the top row. Birefringent images of the fibrous capsules surrounding POSS-SMP-10 are shown as insets. Scale bars: 200 μm. BV = blood vessel; L = lymphocyte; M = macrophage; F = fibroblast; N = neutrophil.

Figure 3

Inflammatory responses to POSS-SMP-10, POSS-SMP-20, POSS-SMP-40 and the PLA control at 164 days post subcutaneous implantation as revealed by H&E (cellularity) and Ki67 (proliferation) immunostaining. Center rows are higher resolution images of the areas boxed in the top row. Birefringent images of the fibrous capsules surrounding POSS-SMPs are shown as insets. Scale bars: 200 μm. BV = blood vessel; L = lymphocyte; M = macrophage; F = fibroblast; N = neutrophil; MNG = multi-nucleated giant cell.

Figure 4

H&E stains of vital organs retrieved from rats receiving A) POSS-SMP-10 for 164 days (500×) revealing no systemic side effects, and B) from age-matched rats without implantation. Scale bars = 200μm.