Bacteria-engineered porous sponge for hemostasis and vascularization

Jie Bian,Wenguo Cui,Feng F Hong,Zhenghui Xiong,Jinhua Huang,Zili Ge,Qiang Zhang,Xiaokang Gao,Xiao Wen,Luhan Bao

doi:10.1186/s12951-022-01254-7

Abstract

BackgroundHemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner.ResultsIn 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.ConclusionThis 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

Highlights

Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner
There is no significant difference among the water absorption rate of bacterial nanocellulose (BNC), oxidized bacterial nanocellulose (OBNC) and OBNC-DFO, but they are significantly faster than collagen hemostatic sponges (COL)
The sponges of BNC origin (BNC, OBNC, and OBNC-DFO) have more pores than COL, further verified by the specific surface area measured by the nitrogen adsorption method

Summary

Introduction

Hemostasis and repair are two essential processes in wound healing, yet early hemostasis and following vascularization are challenging to address in an integrated manner. Intravenous administration of fibrinogen and coagulation factors can significantly modulate the coagulation cascade process, having noticeable effects in controlling bleeding in trauma and injuries. Such products have been extensively studied in preclinical animal models as well as in selected clinical trials [8, 9]. Wound healing is an essential process after hemostasis of trauma, which any of the above hemostatic modalities cannot significantly promote. To deal with the problem of hemostasis and repair in an integrated manner, a biomaterial with early and rapid hemostasis and wound repair functions is urgently required

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