Injectable Nano Whitlockite Incorporated Chitosan Hydrogel for Effective Hemostasis

Abstract

Uncontrolled bleeding can lead to many complications that might cause multiple organ failures and even death. Of all the hemostatic agents used, chitosan has been reported to show better hemostatic potential. It acts through one mechanism involved in hemostasis that is plug formation by adhering to the injured site. Hence our focus is to enhance the hemostatic potential of chitosan (Ch) hydrogel by incorporating nano whitlockite (nWH: Ca18Mg2(HPO4)2(PO4)12) that would release Ca2+, Mg2+, and PO4 3– ions that would simultaneously initiate the coagulation cascade. Ch-nWH composite hydrogel can act simultaneously on different mechanisms involved in hemostasis and bring about rapid bleeding control. The nWH particles were synthesized using precipitation technique and were characterized. Particle size of nWH was found to be 75 ± 5 nm. Composite hydrogel was characterized using FTIR and XRD to confirm the presence of different constituents of the hydrogel. Rheological studies showed the shear-thinning property and increased elastic modulus of the composite hydrogel compared to Ch hydrogel. 2%Ch-4%nWH hydrogel was observed to be cytocompatible with Human Umbilical Vein Endothelial Cells (HUVEC). In the in vitro blood clotting analysis using citrated human whole blood, 2%Ch-4%nWH hydrogel showed rapid blood clot formation compared to control 2%Ch hydrogel. Further in vivo experiments performed on liver and femoral artery injuries created on Sprague–Dawley (S.D) rat model reveals that 2%Ch-4%nWH hydrogel promoted rapid bleeding control and less volume of blood loss compared to Ch hydrogel. These in vitro and in vivo results showed that incorporation of nWH has enhanced the hemostatic potential of Ch hydrogel. Therefore, the synthesized 2%Ch-4%nWH hydrogel may be a promising system that could bring about rapid hemostasis during life threatening bleeding.

Synthesis, Characterization and Process Optimization of Bone Whitlockite

“…Moreover, the weight loss after 700 • C could be attributed to the change of HPO 4 2− into P 2 O 7 and PO 4 and a rapid weight loss after 900 • C could be associated with a unique phenomenon of WH since it converts into TCMP and β-TCP after 700 • C [20,53,54]. The TGA results of WH-6 matches exactly with the previous literature [18,45,46]. Finally, in order to visualize the surface morphology as well as particle size of the WH phase, scanning electron microscopic images of the prepared WH-6 product were obtained.…”

Use of hemostatic agents for surgical bleeding in laparoscopic partial nephrectomy: Biomaterials perspective

“…The product sterilized with the new approach provided a greater adhesion, whereas both chitosan‐based pads provided an effective sealing of the collecting system (Crofton et al, 2019). In a recent study published by Pillai et al, the hemostatic potential of chitosan for severe bleeding was accessed (Muthiah Pillai et al, 2019). The authors formulated an injectable chitosan‐based hydrogel functionalized with nano Whitlockite (nWH: Ca 18 Mg 2 (HPO 4 ) 2 (PO 4 ) 12 )—injectable 2%Ch‐4%nWH composite hydrogel.…”

“…The authors formulated an injectable chitosan‐based hydrogel functionalized with nano Whitlockite (nWH: Ca 18 Mg 2 (HPO 4 ) 2 (PO 4 ) 12 )—injectable 2%Ch‐4%nWH composite hydrogel. The product is hemocompatible and exhibited a rapid and effective hemostasis when compared with a 2% chitosan hydrogel and FloSeal® (Muthiah Pillai et al, 2019).…”

Technology Advancements in Blood Coagulation Measurements for Point-of-Care Diagnostic Testing

“…WH consists of Ca 2+ , Mg 2+ , and PO −3 4 ions which activate different coagulation factors involved in coagulation cascade. Figure 3B illustrates the mechanism of inducing hemostasis by Ch-nWH composite hydrogel, and its rapid and effective hemostasis in in vivo experiment (Muthiah Pillai et al, 2019). Figure 3D shows a hybrid of agar gel and thiolcoated silica nanoparticles immobilized with methylene blue, and the result of aPTT test to monitor heparin.…”

“…(A) Application of nanomaterials in wound healing. (B) Targeted drug delivery system utilizing polyelectrolyte multilayer capsule(Muthiah Pillai et al, 2019). (C) Platelet-hybridized system for targeted delivery of hemostatic agents utilizing polyelectrolyte multilayer capsules(Hansen et al, 2017).…”