When you have a cut or scrapes in your skin, you will normally start to bleed. Cells present in your blood will then start to stick together at the wound site and clot, forming a physical barrier to avoid further blood loss. This clot is mainly composed of a cell type known as platelets and a protein known as fibrin. This clot turns into scabs as they dry with time. This natural mechanism of preventing excessive blood loss may not be sufficient in extensive wounds or surgical cuts or incisions and the body may need extra help. Hemostatic agents (HA) in the form of sponges, gauzes, powder, and paste have been developed to aid in this process. The immediate aim of these agents is to create a physical barrier helping the formation of a clot and accelerating the wound healing. Some of these products are also designed to be biologically active in the sense that it will stimulate the coagulation at the wound site. Despite the availability of commercial HA’s, research is still conducted to develop more effective technologies.
A group of researchers from Dalhousie university led by Dr. Mark Joseph Filiaggi investigated the potential of a specific polymer named sodium polyphosphate (NaPP) to serve as an effective resorbable hemostatic agent. The group had previously developed an in situ-forming embolic agent (composed of the NaPP polymers) used to block blood flow in target blood vessels in the context of a minimally invasive procedure known as embolization. This agent is formed at the wound site as a dense coacervate layer after the addition of two solutions (one containing NaPP and the other containing divalent cations). In their study entitled “Degradation and hemostatic properties of polyphosphate coacervates” published in the journal Acta Biomaterialia, the group evaluated the hemostatic properties of different formulations of this biomaterial by assessing blood or plasma coagulation induced by NaPP.
The authors prepared six formulations of this biomaterial by varying the degree of polymerization (number of the repeating units present in the polymer) and the divalent cations type (calcium, strontium or barium). The hemostatic potential of these formulations was then evaluated using conventional blood clotting assays including whole blood clotting time, prothrombin time (PT), activated partial thromboplastin time (aPTT) and platelet adhesion. Overall, the procedure consisted in adding the biomaterials in a polypropylene tube with the coagulation reagents (depending on the assay) followed by the addition of recalcified blood or plasma. Each tube was gently shaken to visually check for blood or plasma flow. Clotting time was reported as the time required to achieve no flow when the tube was shaken (procedure illustrated in the image below). As controls, the authors also evaluated the clotting time of Surgifoam® (a commercial HA) and of blood or plasma without any biomaterial.
Results from the whole blood clotting time showed that blood without any biomaterial clotted in 7 min and the presence of Surgifoam® did not decrease this time significantly. This was expected since this HA is suggested to serve more as a physical barrier against bleeding rather than altering the blood clotting mechanism. An enthusiastic observation was that 5 (out of 6) formulations of their PP polymer significantly decreased the clotting time by 25 to 60% (depending on the formulation). Similarly, 5 formulations significantly decreased PT compared to the tube with Surgifoam® or empty by roughly 50%. This pronounced decrease is related to the influence of NaPP on thrombin generation reported in literature and consequently on the fibrin clot formation. These results are strong evidence of the great potential of NaPP as a hemostatic agent. Surprisingly, aPTT was significantly increased compared to the control. The authors believe that this result might be an artifact caused by interactions between the polyphosphate chains and phospholipids in the aPTT reagent, reducing the phospholipids available for triggering the coagulation.
Finally, platelet adhesion was evaluated by adding platelets over the surface of the different NaPP formulations and Surgifoam® in a multiwell plate. Platelets adhered in large numbers on the polyphosphate coacervates when compared to Surgifoam® however microscope images showed that their morphological form was related to a more activated state in the commercial HA.
The promising hemostatic potential of polyphosphate coacervates was demonstrated in this study. The fact that this biomaterial can be easily applied or injected at the wound site forming a dense coacervate layer in situ that serve both as a physical and as a biologically active barrier (accelerating the coagulation cascade), and that this biomaterial is afterwards easily resorbed by the body make NaPP a great candidate as a hemostatic agent for clinical use.
Ever fantasized about sci-fi healing tanks? The principle of neutral buoyancy behind them has sparked a unique solution for 3D printing with soft, liquid-like inks. The Freeform Reversible Embedding of Suspended Hydrogels (FRESH) bioprinting technique has been developed to support the printing of these tricky materials, ideal for tissue engineering applications. The secret lies in a cleverly engineered support bath, able to hold the soft structures while permitting extruder needle movement. With versatility, high cell viability, and potential for large construct printing, FRESH opens up a world of possibilities, bringing us a step closer to 3D bioprinting patient-specific tissues based on anatomical data.
Exploring the frontier of 3D printing, Cornell University researchers have enhanced the Freeform Reversible Embedding of Suspended Hydrogels (FRESH) method. They introduced a computational approach for non-planar printing, enabling complex curved structures, improving printing accuracy and augmenting the mechanical properties of bioprints.
4D bioprinting introduces "time" as the fourth dimension, enabling printed objects to change over time. Physical stimuli like light, temperature, or magnetism can induce transformations. The bioprinting process can also allow targeted drug release through changes in temperature or pH. Nano-hydrogels can serve as drug carriers, directed by magnetic fields, and can be quickly degraded by enzymes. Furthermore, hydrogels can react to biological signals, aiding in tumor treatment by releasing drugs then biodegrading over time.
4D-bioprinting introduces "time" into the printing process, allowing printed structures to evolve. Researchers from the University of Illinois Chicago used oxidized and methacrylated alginate (OMA) to develop a bioink for 4D bioprinting. They made OMA into precursor beads, then transformed them into a "microgel" that could be easily printed into stable 3D constructs. Mixed with cells, the microgel became a bioink, which was printed into complex structures. The printed constructs could be further crosslinked to create 3D scaffolds that could change shape due to differential swelling, adding the 4th dimension, "time," to the printing process.
3D-bioprinting involves printing a biomaterial or 'bioink' that contains cells, forming structures similar to living tissues. The process requires careful optimization to ensure the material holds its shape and function, and that the cells survive the printing process. Current bioprinting techniques, such as extrusion, inkjet and laser-assisted bioprinting, come with their own advantages and limitations. The ultimate goal is to bring in vitro bioprinting into the operating room, overcoming challenges like sterility, regulation, and ethical considerations.
Recent advancements in 3D-bioprinting have opened the possibility of creating engineered tissues mimicking human native tissues. However, reproducing the extracellular matrix (ECM) composition and microscopic architecture within the biomaterial ink remains challenging. To tackle this, a research group from the AO Research Institute Davos developed a bioink containing both collagen type 1 and tyramine derivative hyaluronan for tissue engineering. They used optimal concentrations of these two components, along with human bone marrow-derived mesenchymal stromal cells. Two crosslinking pathways were used to induce gelation and create a 3D scaffold that was then printed using the bioink's shear-thinning properties. They successfully printed an anisotropic hydrogel, achieving control over the microscopic organization of the matrix. This breakthrough could pave the way for better mimicry of native human tissues, especially anisotropic ones, in tissue engineering applications.