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 abnormities 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.

Thermal Responsive Shape Memory Polymers for Biomedical Applications

“…Moreover, the multiple -OH end-groups on the macromer provide extra anchors for further attachment of bioactive molecules, as demonstrated by the covalent coupling of fluorescently tagged RGD peptide using "click" chemistry. Finally, using a rat subcutaneous implantation model, we showed that POSS-SMPs were minimally immunogenic and did not elicit pathologic abnormities in any vital/scavenger organs one year after implantation (Filion, 2011).…”

“…In addition, SMP-based biodegradable self-expanding and drug eluting stents (Wache, 2003;Xue, 2010;Yakacki, 2007), biodegradable self-deployable intragastric implants for treating obesity (Klausner, 2003;Pagano & Serezin, 2009), self-fitting vascular and coronary grafts (Sokolowski, 2007), patient-specific customized orthopedic devices (Sokolowski, 2007), tissue engineering scaffolds (Cui, 2011;Filion, 2011;Neuss, 2009;Xu & Song, 2010), and dynamic cell culture substrates (Davis, 2011) have also been explored. One of the most studied biomedical SMPs is cold hibernated elastic memory (CHEM)-processed polyurethane foams for endovascular treatment of aneurysm in animals (Metcalfe, 2003).…”

Responsive Biomaterials: Advances in Materials Based on Shape‐Memory Polymers

“…[42] Interestingly, biodegradable temperature-responsive SMPs based on copolymers of polyhedral oligomeric silsesquioxane and poly(D,L-lactide) implanted subcutaneously in a rat model elicited a mild foreign body type immune response, their degradation rates inversely correlated with the length of the poly(D,L-lactide) chains, and one year after implantation no pathologic abnormities were detected from the vital/scavenger organs examined, highlighting their promise for scaffold-assisted tissue repair. [43] …”

Polyurethane/polyhedral oligomeric silsesquioxane shape memory nanocomposites with low trigger temperature and quick response

“…Compared with shape memory alloys (SMAs) and shape memory ceramics (SMCs), SMPs have higher recoverable strain of several hundred percent, much lower density, lower cost and can be easily processed into complex forms by conventional methods, such as injection molding, film casting, fiber spinning and foaming [2,3]. Therefore, SMPs are steadily expanding their applications in various areas like smart coatings [4], self-deployable structures in spacecraft [5], biomedical applications [6,7], smart actuators [8][9][10] and so on.…”