Bacteria-engineered porous sponge for hemostasis and vascularization

Abstract

Background Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner. Results In this study, we constructed a hemostatic sponge OBNC-DFO by fermentation of Komagataeibacterxylinus combined with TEMPO oxidation to obtain oxidized bacterial nanocellulose (OBNC). Then angiogenetic drug desferrioxamine (DFO) was grafted through an amide bond, and it promoted clot formation and activated coagulation reaction by rapid blood absorption due to the high total pore area (approximately 42.429 m2/g measured by BET). The further release of DFO stimulated the secretion of HIF-1α and the reconstruction of blood flow, thus achieving rapid hemostasis and vascularization in damaged tissue. This new hemostatic sponge can absorb water at a rate of approximate 1.70 g/s, rapidly enhancing clot formation in the early stage of hemostasis. In vitro and in vivo coagulation experiments (in rat tail amputation model and liver trauma model) demonstrated superior pro-coagulation effects of OBNC and OBNC-DFO to clinically used collagen hemostatic sponges (COL). They promoted aggregation and activation of red blood cells and platelets with shorter whole blood clotting time, more robust activation of endogenous coagulation pathways and less blood loss. In vitro cellular assays showed that OBNC-DFO prevailed over OBNC by promoting the proliferation of human umbilical vein endothelial cells (HUVECs). In addition, the release of DFO enhanced the secretion of HIF-1α, further strengthening vascularization in damaged skin. In the rat skin injury model, 28 days after being treated with OBNC-DFO, skin appendages (e.g., hair follicles) became more intact, indicating the achievement of structural and functional regeneration of the skin. Conclusion This hemostatic and vascularization-promoting oxidized bacterial nanocellulose hemostatic sponge, which rapidly activates coagulation pathways and enables skin regeneration, is a highly promising hemostatic and pro-regenerative repair biomaterial. Graphical Abstract

Antibacterial quaternary ammonium chitosan/carboxymethyl starch/alginate sponges with enhanced hemostatic property for the prevention of dry socket

“…As depicted in Figure 3D , the fluid absorption rate of the AC sponge was higher than that of the AG sponge, but not significantly different from that of the ACQ-1 and ACQ-2 sponges. The high fluid absorption rate could enhance the sponge’s ability to absorb blood, which is closely related to the pore size and specific surface area ( Bian et al, 2022 ). Meanwhile, the polysaccharide chain of CMS contains a large number of hydrophilic groups, and the O-H and -COOH groups could enhance the attraction to water molecules ( Yusof et al, 2018 ).…”

Advances in haemostatic sponges: Characteristics and the underlying mechanisms for rapid haemostasis

“…Similarly, on day 21, the OBNC-DFO group's extracellular matrix remodelling, and wound healing phases are almost completed. Tensile Strength BNC: 20.31 kPa OBNC: 40.07 kPa OBNC-DFO: 40.31 kPa COL: 248.51 kPa Youngs Modulus BNC: 1.78 kPa OBNC: 2.70 kPa OBNC-DFO: 2.73 kPa COL: 21.361 kPa Water Absorption rate BNC: 1.71 g/s OBNC: 1.81 g/s OBNC-DFO: 1.70 g/s COL: 0.11 g/s [ 73 ] Collagen fiber oxidized Bletilla striata composite haemostatic sponge (CFOB) OBSP: Oxidized Bletilla striata polysaccharide CF: Collagen fiber The CFOB-0, CFOB-2, CFOB-6, CFOB-10, CFOB-15, and CFOB-20 were obtained by dissolving CF in acetic acid and then gradually adding OBSP to the CF solution and after that the solution was freeze dried. Rat liver haemorrhage model Each material had a different clotting time which was 150.4 ± 29.555 s for blank control, 73 ± 19 s for medical gauze, 50.33 ± 4.51 s for CF, and 25 ± 4.06 s for CFOB-10.…”

“…Similarly, OBNC-DFO haemostatic sponge was prepared by Bian et al which comprises of oxidized bacterial nanocellulose (OBNC) and Desferrioxamine (DFO). The haemostatic ability of OBNC-DFO, OBNC, COL, and BNC sponges was studied in rat tail amputation and liver trauma models which showed that blood loss was 190.47, 160.15, 159.46, 200.26 mg and 200.42, 96.28, 80.44,110.37 mg respectively [ 73 ]. Thus, the high porosity and absorption capacity of the OBNC-DFO sponge make it a promising material with potential for activating coagulation pathways.…”

Bacterial-Nanocellulose-Based Biointerfaces and Biomimetic Constructs for Blood-Contacting Medical Applications

“…It also enhanced proliferation of HUVECs and the secretion of hypoxia-inducible factor 1-alpha, promoting vascularization. 110 While several studies have been performed to investigate various modifications of BNC to enhance its hemostatic potential, there are several limitations of these studies, and more thorough studies of different modifications and methods of modification is required. Several of the modifications discussed in this section include physical grafting rather than chemical grafting, where issues can arise due to grafting stability.…”

“…DFO was chemically grafted on an OBNC sponge through amine bonds and was found to promote clot formation and had a significantly lower blood clotting time and lower blood loss when compared with a clinically used collagen sponge. It also enhanced proliferation of HUVECs and the secretion of hypoxia-inducible factor 1-alpha, promoting vascularization …”