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A liquid-to-solid gelling polymer system, such as the poly(ethylene glycol) diacrylate-pentaerythritol tetrakis (3-mercaptopropionate) (PEGDA-QT) system, can fill cerebral aneurysms more completely than current embolization materials, reducing the likelihood of aneurysm recurrence. PEGDA-QT gels were formulated using PEGDA of different molecular weights (PEGDA575 and PEGDA700), and their characteristics were examined in vitro. Experiments examined gel time, mass change, crosslink integrity, cytotoxicity, and protein release capabilities. In general, PEGDA575-QT gels were more hydrophobic, requiring an initiating solution with a higher pH (pH 9.5) to achieve a gel time comparable to PEGDA700-QT gels, which used an initiating solution at pH 9.19. The mass change and crosslink integrity of gels were analyzed over time after gels were submerged in 150 mM phosphate buffered saline. After 380 days, PEGDA575-QT gels achieved a maximum mass increase of 72% due to water uptake, while PEGDA700-QT gels doubled their initial mass (100% increase) by 165 days. Compression tests showed that PEGDA700-QT gels hydrolyzed more quickly than PEGDA575-QT gels. Cytotoxicity assays showed that in general, PEGDA575-QT negatively affected cell growth, while PEGDA700-QT gels promoted cell viability. Sustained, controlled release of lysozyme, a 14.3 kDa protein, was achieved over an 8-week period when loaded into PEGDA700-QT gels, but PEGDA575-QT gels did not show sustained release. These studies show that although they are similar in composition, these PEGDA-QT gel formulations behave considerably differently. Although PEGDA700-QT gels swell more and degrade faster than PEGDA575-QT gels, their cytocompatibility and protein release characteristics may prove to be more beneficial for in vivo aneurysm treatment., (Copyright © 2013 Wiley Periodicals, Inc.)

Object: Over the past 20 years, endovascular embolization has become the preferred method of treating cerebral aneurysms. While there are many embolic devices on the market, none is ideal. In this study the authors investigated the use of a liquid-to-solid gelling polymer system-that is, poly(propylene glycol) diacrylate and pentaerythritol tetrakis (3-mercaptopropionate) (PPODA-QT)-to embolize in vivo aneurysms over a 6-month period., Methods: Experimental aneurysms were created in the carotid arteries of 9 canines. Aneurysms were embolized with the polymer only (PPODA-QT, 3 dogs), filled with PPODA-QT after placement of a "framing" platinum coil (coil+PPODA-QT, 3 dogs), or packed with platinum coils (coils only, 3 dogs). Aneurysm occlusion was angiographically monitored immediately and 6 months after embolization. After 6 months, the ostial regions of explanted aneurysms were assessed macroscopically and histologically., Results: All aneurysms showed 100% angiographic occlusion at 6 months, but turbulent blood flow was observed in 1 coils-only sample. Ostial regions of explanted coils-only aneurysms showed neointimal tissue surrounding individual coils but no continuous tissue layer over the aneurysm neck. All PPODA-QT aneurysms displayed smooth ostial surfaces, but 2 of 3 coil+PPODA-QT aneurysms showed polymer (unassociated with the coil) protruding into the vessel lumen, contributing to rough ostial surfaces. Neointimal tissue was present in PPODA-QT and coil+PPODA-QT aneurysms and covered smooth ostial surfaces more completely than in coils-only aneurysms., Conclusions: This study compared neointimal tissue overgrowth in the ostium of experimental aneurysms embolized with PPODA-QT, PPODA-QT plus a framing coil, or coils alone. The coils-only and coil+PPODA-QT groups showed rough and discontinuous ostial surfaces, which hindered neointimal tissue coverage. The PPODA-QT aneurysms consistently produced smooth ostial surfaces that facilitated more complete neointimal tissue coverage over aneurysm necks.

A liquid-to-solid gelling polymer system, such as the poly(ethylene glycol) diacrylate-pentaerythritol tetrakis (3-mercaptopropionate) (PEGDA-QT) system, can fill cerebral aneurysms more completely than current embolization materials, reducing the likelihood of aneurysm recurrence. PEGDA-QT gels were formulated using PEGDA of different molecular weights (PEGDA 575 and PEGDA 700 ), and their characteristics were examined in vitro. Experiments examined gel time, mass change, crosslink integrity, cytotoxicity, and protein release capabilities. In general, PEGDA 575 -QT gels were more hydrophobic, requiring an initiating solution with a higher pH (pH 9.5) to achieve a gel time comparable to PEGDA 700 -QT gels, which used an initiating solution at pH 9.19. The mass change and crosslink integrity of gels were analyzed over time after gels were submerged in 150 mM phosphate buffered saline. After 380 days, PEGDA 575 -QT gels achieved a maximum mass increase of 72% due to water uptake, while PEGDA 700 -QT gels doubled their initial mass (100% increase) by 165 days. Compression tests showed that PEGDA 700 -QT gels hydrolyzed more quickly than PEGDA 575 -QT gels. Cytotoxicity assays showed that in general, PEGDA 575 -QT negatively affected cell growth, while PEGDA 700 -QT gels promoted cell viability. Sustained, controlled release of lysozyme, a 14.3 kDa protein, was achieved over an 8-week period when loaded into PEGDA 700 -QT gels, but PEGDA 575 -QT gels did not show sustained release. These studies show that although they are similar in composition, these PEGDA-QT gel formulations behave considerably differently. Although PEGDA 700 -QT gels swell more and degrade faster than PEGDA 575 -QT gels, their cytocompatibility and protein release characteristics may prove to be more beneficial for in vivo aneurysm treatment. © 2013 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater, 2013., (Copyright © 2013 Wiley Periodicals, Inc.)

Objective: Current treatments for cerebral aneurysms are far from ideal. Platinum coils are prone to compaction, and currently used liquid embolics are delivered with angiotoxic agents. This work presents initial in vivo studies of a novel liquid-to-solid gelling polymer system (PPODA-QT), focusing on biocompatibility and effective delivery strategies., Methods: PPODA-QT was used to embolize surgically created lateral wall carotid artery aneurysms in swine using three delivery strategies. Group 1 aneurysms were completely filled with PPODA-QT (n = 5), group 2 aneurysms were subcompletely (80%-90%) filled (n = 3), and group 3 aneurysms underwent three-dimensional coil placement followed by polymer embolization (n = 3). The study was designed such that three animals per treatment group survived to 1 month., Results: The group 1 delivery strategy (100% filling) resulted in survival of 3/5 animals. This strategy led to aneurysm stretching, which resulted model failure in 2/5 animals. Group 2 aneurysms, although initially <100% filled with the polymer, displayed robust neointimal tissue coverage and complete obliteration after 1 month. Group 3 aneurysms showed less prominent neointimal tissue coverage as well as two instances where excess polymer was found in the parent vessel. The PPODA-QT material showed good biocompatibility with vascular tissue in all animals at 1 month., Conclusions: This small-scale pilot study highlighted first-time in vivo use of PPODA-QT as an embolic agent for aneurysm treatment. Filling aneurysms to 80% to 90% capacity proved to be a safe and effective delivery strategy, and PPODA-QT showed excellent biocompatibility. This study indicates that future investigation of PPODA-QT for aneurysm embolization is warranted, as it may prove to be a viable alternative to current embolic materials., (Copyright © 2012 Elsevier Inc. All rights reserved.)

This study examines the in vitro characteristics of a crosslinking polymer system for cerebral aneurysm embolization. The polymeric material is composed of poly(propylene glycol)diacrylate (PPODA) and pentaerythritol tetrakis(3-mercaptopropionate) (QT), formulated with the liquid contrast agents Conray™ or Omnipaque™ 300. The PPODA-QT system was tested for delivery feasibility through mock delivery into a model aneurysm. Cytotoxicity was performed by exposing 3T3 cells to gel formulations, followed by a cell viability assay. Swelling was measured on samples submerged in 150 mM phosphate buffered saline at 37 or 50°C. The same samples underwent compression testing to assess degradation, characterized by reduction in Young's modulus over time. The PPODA-QT system was easily deliverable to mock aneurysms. Cytotoxicity results indicated that Conray-formulated gels are initially less toxic than Omnipaque-formulated gels, but show greater susceptibility to swelling and degradation over time. In general, these experiments represented more challenging conditions than would be present in vivo, and therefore, reported results are likely overestimations of in vivo outcomes. However, these results highlight potential issues with each PPODA-QT formulation. Given the desired outcome of neointimal tissue growth over the polymer material, initial cytotoxicity may be more important than long-term factors when choosing an optimal formulation for aneurysm embolization., (Copyright © 2012 Wiley Periodicals, Inc.)