All-Aqueous Microfluidics Fabrication of Multifunctional Bioactive Microcapsules Promotes Wound Healing

Abstract

Wound healing involves multiple stages of body responses, including hemostasis, inflammation, cell proliferation, and tissue remodeling. New material design satisfying all demands throughout different stages of wound healing is cherished but rarely discussed. Here we introduce all-aqueous multiphase microfluidics as a novel strategy to fabricate self-assembled, multifunctional alkylated chitosan/alginate microcapsules (SAAMs) as novel therapeutic materials for rapid blood coagulation and wound healing. SAAMs are structurally distinguished by their ultrathin shells with polycationic surface for rapid activation of clotting cascade and their internal porous dextran-rich cores for fast absorption of blood and exudate. These features endow SAAMs with excellent hemostatic properties for acute hemorrhage. Moreover, the alkylated chitosan within the microcapsules exhibits persistent antimicrobial activities against bactericidal infections due to their amphiphilic and cationic surfaces. Besides, cytokines can be safely loaded into the organic-solvent-free microcapsules and released precisely to promote the proliferation of epidermal cells, supporting the subsequent development of granulation tissue and suppression of inflammation in the last stages of wound healing. With the ability to fabricate size-tailored soft microcapsules and to realize time-sequential functions for tissue repairing, the presented "all-aqueous microfluidics generation of multifunctional bioactive SAAMs" create a versatile and robust paradigm for wound treatment.

Robust and Wet Adhesive Self-Gelling Powders for Rapid Hemostasis and Efficient Wound Healing

“…The fast gelation has further been proved quantitatively using a rheometer, in which the storage modulus ( G ′) of (PEI/PDDA)/(PAA/PSS)/ACS self-gelling powders intersects with the loss modulus ( G ″) at 3 s upon adding phosphate-buffered saline (PBS) buffer (Figure G). A higher storage modulus ( G ′) than the loss modulus ( G ″) indicates the successful transformation from powders to hydrogels. , The gelation time of other similar hydrogel powders has been reported to be around 2 s , The prolonged gelation time of our self-gelling powders is due to the incorporation of ACS, whose hydrophobicity would affect the interaction between its polymeric chains and the surrounding liquid.…”

“…Severe trauma wounds can cause devastating consequences, including fatal blood loss, shock, infection, and life-threatening injuries . Achieving rapid hemostasis hence becomes vital during wound management. , Wound caring in clinical research has attracted a surge of interest from the science community, with a primary concern on developing ideal wound dressing, which should hold the following requirements: rapid blood cell aggregation to halt bleeding (hemostasis), strong adhesion on the bleeding wounds without the need of compression, sufficient mechanical properties to provide a physical barrier on the wounds to maintain blood pressure, good hemocompatibility and biocompatibility, and continuous protection against bacterial infection. − …”

“…29,30 Our previous work has demonstrated that alkylated chitosan (ACS) utilizes its long carbon chain to anchor cell membranes and achieve efficient hemostasis. 5 It also exhibits antimicrobial properties by effectively preventing wound infection and inflammation. 31 Nevertheless, when incorporated into the self-gelling polymer matrix as a functional component, the positive charges carried by ACS would deteriorate the cross-linking of polymer gels like PEI and PAA, 28 thereby diminishing the strength of the resulting gel and hindering their practical potential.…”

Triboelectric Nanogenerators-Based Therapeutic Electrical Stimulation on Skin: from Fundamentals to Advanced Applications

“…The process of wound healing can be divided into three stages, which include inflammatory, proliferative, and remodeling. − In the early and entire phase of inflammation, the accelerated recruitment of cytokines and immune cells is very important. It has been shown that endogenous electric fields can promote the migration of macrophages, lymphocytes, and neutrophils to skin wound sites and ultimately promote wound healing .…”

Zwitterionic nanocapsule-based wound dressing with the function of gradient release of multi-drugs for efficient wound healing

“…[14][15][16] From the perspective of the treatment strategy, hemostasis and remodeling could be achieved well passively by the body itself: the aggregation of platelets and the formation of fibrin clots could stop bleeding effectively, while the generated collagen in the proliferation stage would arrange and cross-link to achieve structural and mechanical remodeling. [17][18][19] Different from hemostasis and remodeling, active drug intervention (such as antibiotics and growth factors) is usually additionally required in the inflammation and proliferation stages to help the human body kill foreign organisms and promote the growth of new tissue. [20][21][22][23] Therefore, it is highly desired to construct a multidrug loaded wound dressing with a controlled gradient drug release kinetics to meet the diverse requirements of the drug type and release time point at the inflammation and proliferation stages.…”