ABSTRACT
The tissue-specific heart decellularized extracellular matrix (hdECM) demonstrates a variety of therapeutic advantages, including fibrosis reduction and angiogenesis. Consequently, recent research for myocardial infarction (MI) therapy has utilized hdECM with various delivery techniques, such as injection or patch implantation. In this study, a novel approach for hdECM delivery using a wet adhesive paintable hydrogel is proposed. The hdECM-containing paintable hydrogel (pdHA_t) is simply applied, with no theoretical limit to the size or shape, making it highly beneficial for scale-up. Additionally, pdHA_t exhibits robust adhesion to the epicardium, with a minimal swelling ratio and sufficient adhesion strength for MI treatment when applied to the rat MI model. Moreover, the adhesiveness of pdHA_t can be easily washed off to prevent undesired adhesion with nearby organs, such as the rib cages and lungs, which can result in stenosis. During the 28 days of in vivo analysis, the pdHA_t not only facilitates functional regeneration by reducing ventricular wall thinning but also promotes neo-vascularization in the MI region. In conclusion, the pdHA_t presents a promising strategy for MI treatment and cardiac tissue regeneration, offering the potential for improved patient outcomes and enhanced cardiac function post-MI.
Subject(s)
Decellularized Extracellular Matrix , Disease Models, Animal , Hydrogels , Myocardial Infarction , Rats, Sprague-Dawley , Animals , Rats , Hydrogels/chemistry , Decellularized Extracellular Matrix/chemistry , Male , Extracellular Matrix/chemistry , MyocardiumABSTRACT
Chitosan (Cs) as a hemostatic agent has been in use to control hemorrage. Composite hydrogel formed by entrapment of vasoconstrictor-potassium aluminium sulfate (0.25 %PA) and coagulation activator-calcium chloride (0.25 %Ca) into Cs (2 %) hydrogel would enhance the hemostatic property of Cs. In this work, the prepared composite hydrogel was injectable, shear thinning, cyto and hemocompatible. The 2 %Cs-0.25 %PA-0.25 %Ca composite hydrogel caused rapid blood clotting by accelerating RBC/platelet aggregation and activation of the coagulation cascade. Further, in vivo studies on rat liver and femoral artery hemorrage model showed the efficiency of 2 %Cs-0.25 %PA-0.25 %Ca composite hydrogel to achieve hemostasis in a shorter time (20 ± 10 s, 105 ± 31 s) than commercial hemostatic agents-Fibrin sealant (77 ± 26 s, 204 ± 58 s) and Floseal (76 ± 15 s, 218 ± 46 s). In in vivo toxicological study, composite hydrogel showed material retention even after 8 weeks post-surgery, therefore excess hydrogel should be irrigated from site of application. This prepared composite hydrogel based hemostatic agent has potential application in low pressure bleeding sites.
Subject(s)
Chitosan/chemistry , Hemorrhage , Hydrogels/chemistry , Vasoconstriction/drug effects , Animals , Blood Coagulation , Blood Platelets/metabolism , Calcium/chemistry , Erythrocytes/cytology , Femoral Artery/metabolism , Femoral Artery/pathology , Hemostasis , Hemostatics/pharmacology , Human Umbilical Vein Endothelial Cells , Humans , Liver/blood supply , Male , Platelet Aggregation , Rats , Rats, Sprague-Dawley , Swine , Vasoconstrictor Agents/pharmacologyABSTRACT
Effective bleeding control is a major concern in trauma and major surgeries. Chitosan (Ch) as hemostatic agent has been widely used and when applied at the site of injury it acts by aggregating blood cells and forming a plug. Our prime interest is to improve the blood clotting property of Ch hydrogel. Incorporation of nanobioglass (nBG) with silica (activate coagulation factor XII), calcium (activate intrinsic pathway) and phosphate (initiates extrinsic pathway) ions into Ch hydrogel (protonated NH2 group) would act at the same time and bring about rapid blood clot formation. Sol-gel method was followed to synthesize nBG particles and its particle size was found to be 14⯱â¯3â¯nm. 2%Ch-5%nBG hydrogel was then prepared and studied using SEM and FTIR. The prepared hydrogel was injecable and was also cytocompatible with HUVEC. In in vitro blood clotting study and in vivo major organ injury model, 2%Ch-5%nBG hydrogel formed rapid blood clot than 2%Ch hydrogel. Hence, 2%Ch-5%nBG hydrogel might have great potential to achieve effective bleeding control during critical situations.
Subject(s)
Ceramics , Chitosan , Hemostasis , Hydrogels , Nanoparticles , Animals , Biocompatible Materials/chemistry , Blood Coagulation , Ceramics/chemistry , Chitosan/chemistry , Hydrogels/chemistry , Nanoparticles/chemistry , Nanoparticles/ultrastructure , Rats , RheologyABSTRACT
A braided multiscale fibrous scaffold consisting of aligned PCL micro/collagen-bFGFnano fibers was fabricated (mPCL-nCol-bFGF) to mimic native tendon tissue architecture which was further coated with alginate to aid in prevention of peritendinous adhesion. The bFGF release kinetics showed a sustained release of growth factors for a period of 20 days. Further, in vitro cell viability, attachment, and proliferation were performed using rabbit tenocytes under static and dynamic conditions. mPCL-nCol-bFGF showed a higher cell proliferation and enhanced expression of tenogenic markers compared to mPCL-nCol (braided scaffold without bFGF). When subjected to dynamic stimulation in a bioreactor, mPCL-nCol-bFGF-DS (braided scaffold with bFGF after dynamic stimulation) showed enhanced cellular proliferation and tenogenic marker expression, compared to mPCL-nCol-bFGF. The in vivo studies of the cell seeded scaffold after dynamic stimulation in Achilles tendon defect model showed tendon tissue regeneration with aligned collagen morphology within 12 weeks of implantation.
