Preparation of electrospun core-sheath yarn with enhanced bioproperties for biomedical materials.

OBJECTIVES: To create a multifunctional medical material that combines the advantages of both nanofibers and macroyarns. RESULTS: A novel electrospinning-based approach was developed for creating polycaprolactone (PCL) nanofiber covered yarns (PCL-NCYs) in which polyglycolic acid multi-strand filaments (PGA-MFs) were used as the core. BALB/3T3 (mouse embryonic fibroblast cell line) cells were cultured on the PCL-NCYs substrate and cell morphology and proliferation were determined by methylthiazol tetrazolium (MTT) assay. Compared with PGA-MFs, PCL-NCYs had a higher porosity and tensile strength of 88 ± 8% and 348 ± 16 MPa and in particular, the porosity was four times higher. BALB/3T3 cells attached more easily onto the nanofiber structure and proliferated along the direction of nanofibers, indicating that PCL-NCYs can achieve better cell differentiation and proliferation. CONCLUSIONS: PCL-NCYs can be created by combining electrospinning covering and textile twisting, and have better mechanical property and higher porosity, and can be used as a novel scaffold in tissue engineering.

Chitosan thermogelation and cascade mineralization via sequential CaCO3 incorporations for wound care.

Physically crosslinked hydrogels have shown great potential as excellent and eco-friendly matrices for wound management. Herein, we demonstrate the development of a thermosensitive chitosan hydrogel system using CaCO3 as a gelling agent, followed by CaCO3 mineralization to fine-tune its properties. The chitosan hydrogel effectively gelled at 37 °C and above after an incubation period of at least 2 h, facilitated by the CaCO3-mediated slow deprotonation of primary amine groups on chitosan polymers. Through synthesizing and characterizing various chitosan hydrogel compositions, we found that mineralization played a key role in enhancing the hydrogels' mechanical strength, viscosity, and thermal inertia. Moreover, thorough in vitro and in vivo assessments of the chitosan-based hydrogels, whether modified with mineralization or not, demonstrated their outstanding hemostatic activity (reducing coagulation time by >41 %), biocompatibility with minimal inflammation, and biodegradability. Importantly, in vivo evaluations using a rat burn wound model unveiled a clear wound healing promotion property of the chitosan hydrogels, and the mineralized form outperformed its precursor, with a reduction of >7 days in wound closure time. This study presents the first-time utilization of chitosan/CaCO3 as a thermogelation formulation, offering a promising prototype for a new family of thermosensitive hydrogels highly suited for wound care applications.

Development of alginate macroporous hydrogels using sacrificial CaCO3 particles for enhanced hemostasis.

Polymeric hydrogels have increasingly garnered attention in the field of hemostasis. However, there remains a lack of targeted development and evaluation of non-dense polymeric hydrogels with physically incorporated pores to enhance hemostasis. Here, we present a facile route to macroporous alginate hydrogels using acid-induced CaCO3 dissolution to provide Ca2+ for alginate gelation and CO2 bubbles for subsequent macropore formation. The as-prepared pore structure in the hydrogels and its formation mechanisms were characterized through microscopic imaging and nitrogen adsorption/desorption tests. Functional analyses revealed that the macroporous hydrogels exhibited improved rheology, blood absorption, coagulation factor delivery, and platelet aggregation. Ultimately, the introduction of pores significantly enhanced the hemostatic effectiveness of alginate hydrogels in vivo, as demonstrated in rat tail amputation and liver injury models, leading to a reduction in blood loss of up to 77 % or a decrease in bleeding time of up to 88 %. Notably, hydrogels with higher porosity achieved with a CaCO3 to alginate ratio of 40 % outperformed those with lower porosity in the aforementioned properties. Furthermore, these improvements were found to be biocompatible and elicited minimal inflammation. Our findings underscore the potential of a simple porous hydrogel design to enhance hemostasis efficacy by physically incorporating macropores.

Incorporation of tissue factor-integrated liposome and silica nanoparticle into collagen hydrogel as a promising hemostatic system.

Bleeding complications are associated with substantial tissue morbidities and mortalities. Biomimetic composite materials that possess the ability to sufficiently stimulate and augment different physiological mechanisms of hemostasis are highly desirable to reduce bleeding-related casualties, which, however, are still largely under-explored. This study aims to develop a composite hemostatic system by combining collagen hydrogel with tissue factor (TF)-integrated liposome and silica nanoparticle, which could integrate the platelet plug-promoting capacity of collagen with the abilities of the latter two components to activate the extrinsic and intrinsic pathways of coagulation respectively. Several hydrogel compositions were synthesized and characterized. We show that lipidated TF and silica were evenly distributed in the collagen-based hydrogels, while exhibiting tunable release kinetics in simulated body fluid. Time-to-coagulation test revealed that each component in the TF-liposome/silica/collagen ternary hydrogels was hemostasis-active, and their combination showed enhanced and potent procoagulant performance, without detectable cytotoxicity against NIH/3T3 model cells. These results suggest that collagen hydrogels with embedded TF-liposome and silica nanoparticle may serve as a platform for an effective hemostatic composite that incorporates all the basic known pathways of coagulation.

Armoring a liposome-integrated tissue factor with sacrificial CaCO3 to form potent self-propelled hemostats.

The development of hemostatic materials suitable for diverse emergency scenarios is of paramount significance, and there is growing interest in wound-site delivery of hemostasis-enhancing agents that can leverage the body's inherent mechanisms. Herein we report the design and performance of a biomimetic nanoparticle system enclosing tissue factor (TF), the most potent known blood coagulation trigger, which was reconstituted into liposomes and shielded by the liposome-templated CaCO3 mineralization. The mineral coatings, which mainly comprised water-soluble amorphous and vateritic phases, synergized with the lipidated TF to improve blood coagulation in vitro. These coatings served as sacrificial masks capable of releasing Ca2+ coagulation factors or propelling the TF-liposomes via acid-aided generation of CO2 bubbles while endowing them with high thermostability under dry conditions. In comparison to commercially available hemostatic particles, CaCO3 mineralized TF-liposomes yielded significantly shorter hemostasis times and less blood loss in vivo. When mixed with organic acids, the CO2-generating formulation further improved hemostasis by delivering TF-liposomes deep into actively bleeding wounds with good biocompatibility, as observed in a rat hepatic injury model. Therefore, the designed composite mimicry of coagulatory components exhibited strong hemostatic efficacy, which in combination with the propulsion mechanism would serve as a versatile approach to treating a variety of severe hemorrhages.

Preparation and characterization of tissue-factor-loaded alginate: Toward a bioactive hemostatic material.

Tissue factor (TF), an integral membrane protein, is by far the most potent known triggering agent of blood coagulation. Inspired by TF's effectiveness in initiating coagulation, this work aims to develop hemostatic materials with TF-integrated liposomes, which combined with alginate biopolymers are designed as composite pastes or hydrogels cross-linked with Ca2+. Fluorescence measurements revealed that the proteoliposomes were evenly distributed within alginate matrices, which also remained intact after release into simulated body fluid. The proteoliposome release rate from the composite pastes increased with the decrease of alginate concentration from 3% to 1%, or relative to the corresponding hydrogels. The latter also showed a swelling property. The combination with alginate enhanced TF procoagulant activity, and most importantly the resultant composites exhibited superior hemostatic performance, yielding a shortest blood clotting time of 1.5 min while untreated blood took 14.2 min to clot, with no cytotoxicity against mammalian cells.