ABSTRACT
Tissue adhesives and sealants offer promising alternatives to traditional wound closure methods, but the existing trade-off between biocompatibility and strength is still a challenge. The current study explores the potential of a gelatin-alginate-based hydrogel, cross-linked with a carbodiimide, and loaded with two functional fillers, the hemostatic agent kaolin and cellulose fibres, to improve the hydrogel's mechanical strength and hemostatic properties for use as a sealant. The effect of the formulation parameters on the mechanical and physical properties was studied, as well as the biocompatibility and microstructure. The incorporation of the two functional fillers resulted in a dual micro-composite structure, with uniform dispersion of both fillers within the hydrogel, and excellent adhesion between the fillers and the hydrogel matrix. This enabled to strongly increase the sealing ability and the tensile strength and modulus of the hydrogel. The fibres' contribution to the enhanced mechanical properties is more dominant than that of kaolin. A combined synergistic effect of both fillers resulted in enhanced sealing ability (247%), tensile strength (400%), and Young's modulus (437%), compared to the unloaded hydrogel formulation. While the incorporation of kaolin almost did not affect the physical properties of the hydrogel, the incorporation of the fibres strongly increased the viscosity and decreased the gelation time and swelling degree. The cytotoxicity tests indicated that all studied formulations exhibited high cell viability. Hence, the studied new dual micro-composite hydrogels may be suitable for medical sealing applications, especially when it is needed to get a high sealing effect within a short time. The desired hemostatic effect is obtained due to kaolin incorporation without affecting the physical properties of the sealant. Understanding the effects of the formulation parameters on the hydrogel's properties enables the fitting of optimal formulations for various medical sealing applications.
Subject(s)
Alginates , Cellulose , Hemostatics , Hydrogels , Kaolin , Materials Testing , Tensile Strength , Tissue Adhesives , Cellulose/chemistry , Cellulose/pharmacology , Hemostatics/chemistry , Hemostatics/pharmacology , Tissue Adhesives/chemistry , Tissue Adhesives/pharmacology , Hydrogels/chemistry , Hydrogels/pharmacology , Alginates/chemistry , Kaolin/chemistry , Kaolin/pharmacology , Humans , Biocompatible Materials/chemistry , Biocompatible Materials/pharmacology , Elastic Modulus , Viscosity , Animals , Gelatin/chemistry , Mice , Cell Survival/drug effectsABSTRACT
Pain is one of the most common patient complaints encountered by health professionals and remains the number one cause of absenteeism and disability. In the current study, analgesic-eluting bioresorbable porous structures prepared using the freeze-drying of inverted emulsions technique were developed and studied. These drug-eluting structures can be used for coating fibers or implants, or for creating standalone films. They are ideal for forming biomedically important structures that can be used for various applications, such as wound dressings that provide controlled release of analgesics to the wound site in addition to their wound dressing role. Our investigation focused on the effects of the inverted emulsion's parameters on the shell microstructure and on the resulting drug-release profile of ibuprofen and bupivacaine. The release profiles of ibuprofen formulations exhibited a diffusion-controlled pattern, ranging from several days to 21 days, whereas bupivacaine formulations exhibited an initial burst release followed by a three-phase release pattern over a period of several weeks. Higher organic to aqueous phase ratios and higher polymer contents reduced the burst release of both drugs and prolonged their release due to lower porosity. Overall, the drug-eluting porous structures loaded with either ibuprofen or bupivacaine demonstrated a promising potential for use in various applications that require pain relief.