Thomas H. Jozefiak

Free radical polymerization of poly(ethylene glycol) diacrylate macromers: Impact of macromer hydrophobicity and initiator chemistry on polymerization efficiency

A series of poly(ethylene glycol)-co-poly(lactide) diacrylate macromers was synthesized with variable PEG molecular weights (10 or 20 kDa) and lactate contents (0 or 6 lactates per end group). These macromers were polymerized to form hydrogels by free radical polymerization using either redox or photochemical initiators. The extent of polymerization was determined by monitoring the compressive modulus of the resulting hydrogels and by quantitative determination of unreacted acrylate after exhaustive hydrolysis of the gel. Polymerization efficiency was found to depend on the lactate content of the macromer, with higher lactate macromers giving more efficient polymerization. For redox-initiated polymerization using ferrous gluconate/t-butyl hydroperoxide initiator, macromers containing approximately six lactate repeats per end group required lower concentrations of initiator to reach high conversion than lactate-free macromers. Photochemical polymerization with α,α-dimethoxy-α-phenylacetophenone (Irgacure 651(®)) was found to be less efficient than redox polymerization, requiring the addition of N-vinyl-2- pyrrolidone (NVP) as a co-monomer to achieve conversions comparable with redox polymerization. When conditions were optimized to provide near complete conversion for all gels, the presence of lactate repeat units in the hydrogel was generally found to reduce swelling and increase the compressive modulus. Calculated values of molecular weight between cross-links (M(c)) and mesh size using Flory-Rehner theory showed that macromer molecular weight had the greatest impact on the network structure of the gel.

Remote Efficacy for Two Different Forms of Hyaluronate-Based Adhesion Barriers

ABSTRACT Background: Chemically modified sodium hyaluronate and carboxymethylcellulose (HA/CMC) membrane clinically reduces adhesion formation following surgery but was not designed for laparoscopic use. HA/CMC powder of identical chemical composition has been developed to allow for application laparoscopically. We compared the adhesion reduction efficacy of HA/CMC powder and film when applied directly to or remote from sites of surgical trauma. We also investigated the effect of the powder on wound healing. Materials and Methods: Two animal models of adhesion formation were used to evaluate efficacy: a rat peritoneal sidewall defect model and a rabbit cecal abrasion/sidewall defect model. The products were applied directly to the defect or the contralateral sidewall. Adhesions were examined seven days after surgery. In a separate study, the effect of the powder on healing was evaluated at 5, 7, and 28 days using a rat incisional wound strength model. Results: HA/CMC powder and film, when applied directly to the peritoneal defect, significantly reduced adhesions relative to the untreated control in both models. Remote applications of HA/CMC powder also reduced adhesions. In contrast, remote applications of HA/CMC film had no effect. HA/CMC powder did not significantly alter incisional wound strength at any of the timepoints tested. Conclusion: In our preclinical models, HA/CMC powder had similar adhesion reduction efficacy to HA/CMC film when applied directly to sites of trauma. In addition, HA/CMC powder reduced adhesions remote from the application site. Importantly, HA/CMC powder did not impair incisional wound healing. On the basis of these results, future investigation of HA/CMC powder is warranted.