Poor postoperative healing after sinus surgery is associated with high concentrations of matrix metalloproteinase-9 (MMP-9). The frontal recess is especially vulnerable to restenosis, and frontal sinus stents have been used to overcome this problem. However, the long-term success rate is still controversial and may be poor. In this perspective, we developed doxycycline (DC)-releasing stents, delivering the MMP-9 synthesis-suppressing agent locally to the frontal recess area. We evaluated postoperative MMP-9 levels, bacterial colonization, healing quality, and symptom scores in patients suffering from chronic rhinosinusitis with (CRSwNP) and without nasal polyposis (CRSsNP) (n=10) who underwent functional endoscopic sinus surgery during which the DC-releasing and placebo stents were placed. We found that MMP-9 concentrations were significantly lower at the side of the DC-releasing stent (3,414+/-582 ng/mL) compared with the contralateral placebo stent (9,172+/-2,564 ng/mL) (p<0.05) at month 3 postsurgery. DC stents adequately suppressed bacterial growth compared with placebo stents. Furthermore, the visual analog scale (VAS) for the frontal region was significantly better (mean value 75.1 vs. 52.8, p<0.001) compared with its placebo counterpart. We conclude that compared with placebo stents, DC-releasing stents significantly lowered MMP-9 concentrations and bacterial colonization locally, and improved postoperative healing quality after functional endoscopic sinus surgery, as demonstrated by visual analog scale and ostial closure.

We first describe the use of a cytokine-releasing stent to stimulate collateral artery growth. These results show that intra-arterial cytokine-releasing devices might serve as a novel platform for the delivery of compounds affecting biological processes downstream of the site of implantation.

Summary: Branched poly(L‐lactide)‐poly(ethylene glycol) (PLLA‐PEG) block copolymers were synthesized from trifunctional PLLA and amine functionalized methoxy poly(ethylene glycol)s. The copolymers in water formed hydrogels that showed thermo‐responsive behavior. The hydrogels underwent a gel to sol transition with increasing temperature as determined with the vial tilting method and oscillatory rheology. For all copolymers, the transition temperature increased with increasing copolymer concentration. The transition temperature of corresponding branched copolymers also increased with increasing PEG molecular weight, and surprisingly decreased with increasing molecular weight of the PLLA branches. In general, the gel‐sol transition is explained by disruption of micellar or aggregate interactions because of partial dehydration and shrinkage of the PEG chains. An increase in the molecular weight of the PLLA branches led to the formation of micelles and aggregates as observed with DLS at low concentrations. It is speculated that the non‐uniform size distribution and possible crystallization of longer PLLA blocks may have a negative effect on the formation of micellar packing upon gelation, allowing the disruption of micellar or aggregate interactions to occur at lower temperatures. The transition temperature of the gels could be tuned closely to body temperature by varying the concentration of the solution or the molecular weight of the PEG block and the PLLA blocks, which implies that these polymers may be used as injectable systems for in‐situ gel formation.

The reaction of mixtures of pivalolactone (PVL), alkanediols, and dimethyl terephthalate (DMT) was investigated in a two-stage melt process. NMR measurements (XH, 13C,-, 1H-13C) indicated that poly(ether ester)s had been formed. Apart from a significant amount of ether bonds, the copolymers contained practically no PVL sequences, which was also observed using a model system consisting of bis-(hydroxybutyl) terephthalate and PVL. From the results of the model study it was concluded that ring opening of PVL had occurred by attack on the /3-carbon atom, followed by alkyl-oxygen bond scission, thus leading to the formation of ether bonds. Furthermore, it was found that propagation through successive attacks on PVL had not taken place; instead the formed carboxylic acid end groups reacted with hydroxyl groups, resulting in isolated PVL units in the polymeric chains. In this paper also data are presented about the effect of the catalyst and of the type of lactone on the copolymer synthesis.

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