Introduction: Our aim is to develop and evaluate a novel tissue sealant utilizing the universal adhesion reaction based on multivalent interactions between phosphatidyl choline (PC) lipid head groups on cell membranes and synthetic choline phosphate (CP)–containing polymers[1]. Such polymers when electrospun into pads should both adhere to solid tissue and bind red blood cells (RBCs) and platelets to arrest bleeding at sites of tissue damage or surgery where vascular integrity is breached. These polymer webs should meet the mechanical and functional requirements for wound healing and blood conservation applications[2]-[5].
Materials and Methods: A nano scale fiber web consisting of a random copolymer containing the backbone of ε-caprolactone and its derivative with a pendent hydrophilic segment bearing functional CP groups was prepared by the electrospinning process. To achieve the copolymer, a new cyclic ester, γ-(2-bromo-2-methly propionyl)-ε-caprolactone, containing a pendent-activated alkyl bromide functional group was prepared[6]. This new monomer serves as both a monomer for ring-opening polymerization (ROP) with ε-caprolacone as well as an initiator for controlled atom transfer radical polymerization (ATRP). The random co-poly(caprolactone) via ROP was tuned to make a suitable candidate for the electrospin process, balancing hydrophobicity, hydrophilicity and the density of functional groups by adjusting the ratio of new monomer and ε-caprolactone. The synthesis of poly(ε-caprolactone)-graft- poly(2-(2-(2-(2-azidoethoxy) -ethoxy)ethoxy)ethyl methacrylate) was via a grafting-from technique, where poly(caprolactone) with pendent isobutyryl bromide groups acted as macroinitiator to initiate the ATRP azido monomer to yield the grafted copolymer containing a backbone of poly(caprolactone) and dispersed side chains of poly(methacrylate) with multiple azido groups. Finally, pre-prepared prop-2-ynyle phosphatidylcholine (CP monomer) was clicked onto the above grafted copolymer via the reaction between the pendent azido groups of the copolymer and the alkyne group of CP monomer. The CP monomer (prop-2-ynyle phosphatidylcholine) was prepared following our previously reported method[1]. The designed copolymers were characterized with NMR and FTIR to determine the MW and presence of functional groups and the electrospun web with SEM.
Results and Discussion: Human RBCs incubated with the CP web formed a uniform layer on the mat surface attributed to multivalent interactions between CP groups on the web and PC groups on the cell membrane, demonstrating the material’s potential for blood conservation and sealing.
Incubation in isotonic whole blood with reduced ionic strength resulted in enhanced adhesion and supports an electrostatic mechanism for the CP-PC association.
Conclusion: We anticipate that this functional fiber mat will prove to be a fundamentally new and effective biomaterial for wound dressing and blood conservation practice.
References:
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