A tissue sealant based on reactive multifunctional polyethylene glycol

A rapidly gelling synthetic tissue sealant was developed from tetra-succini midyl and tetra-thiol-derivatized polyethylene glycol (PEG). The two reagen ts were dissolved in aqueous buffers at 20% (w/v) solids and sprayed on the tissue site, with the use of a sprayer/mixer device. Good adhesion to coll agen membranes, PTFE grafts, and carotid artery was observed in vitro. In a burst test on collagen membranes with a 2-mm orifice defect, the gel susta ined fluid pressures of 125 +/- 36 mm Hg (n = 18), fivefold greater than ca pillary blood pressure and one-half that observed in hypertension. On 0.4-m m-diameter puncture defects in PTFE grafts, pressures of 390-490 mm Hg were sustained, and on 0.6-0.9-mm puncture defects in carotid arteries, pressur es of 490 to 840 mm Hg were sustained. In vitro data corresponded to result s in vivo, where bleeding in rabbit arteries was stopped immediately in fiv e out of six trials. A significant reduction in time to hemostasis and bloo d loss, compared to controls, was observed. Carotid artery and subcutaneous implant data in rabbits showed that the formula was compatible with biolog ical tissue. Rapid gelling and effective sealing were dependent on the pres ence of active succinimidyl ester and thiol groups on PEG. HPLC and chemica l substitution methods were useful in predicting whether batches of derivat ized PEG would perform satisfactorily. (C) 2001 John Wiley & Sons, Inc.