Safe and Efficacious Near Superhydrophobic Hemostat for Reduced Blood Loss and Easy Detachment in Traumatic Wounds.

Hemorrhage is the leading cause of trauma death, and innovation in hemostatic technology is important. The strongly hydrophobic carbon nanofiber (CNF) coating has previously been shown to have excellent hemostatic properties. However, the understanding of how CNF coating guides the coagulation cascade and the biosafety of CNF as hemostatic agents has yet to be explored. Here, our thrombin generation assay investigation showed that CNF induced fast blood coagulation via factor (F) XII activation of the intrinsic pathway. We further performed studies of a rat vein injury and demonstrated that the CNF gauze enabled a substantial reduction of blood loss compared to both the plain gauze and kaolin-imbued gauze (QuikClot). Analysis of blood samples from the model revealed no acute toxicity from the CNF gauze, with no detectable CNF deposition in any organ, suggesting that the immobilization of CNF on our gauze prevented the infiltration of CNF into the bloodstream. Direct injection of CNF into the rat vein was also investigated and found not to elicit overt acute toxicity or affect animal survival or behavior. Finally, toxicity assays with primary keratinocytes revealed minimal toxicity responses to CNF. Our studies thus supported the safety and efficacy of the CNF hemostatic gauze, highlighting its potential as a promising approach in the field of hemostatic control.

Highly Stretchable, Swelling-Resistant, Self-Healed, and Biocompatible Dual-Reinforced Double Polymer Network Hydrogels.

Superior flexibility and toughness can be achieved in bioactive hydrogels by the use of a double polymer network with complementary properties. Inspired by this design principle, we here combine polyacrylic acid (PAA) and sodium alginate (SA) to obtain a dual-reinforced double interpenetrating network (d-DIPN) hydrogel. The dual reinforcement involves ionic cross-linking and introduction of SiO2 nanoparticles, which leads to extraordinary improvements in strength and toughness. Compared with the standard PAA hydrogel that offers an elongation of 240% and a breakage stress of 0.03 MPa, the prepared SA(Ca2+)-PAA-SiO2 hydrogel shows an elongation above 1000% and a breakage stress of 1.62 MPa. Moreover, the combination of strong covalent cross-links and weak reversible interactions provides the d-DIPN hydrogel with swelling resistance and self-healing behavior, adhesive abilities, and shape memory performance. Furthermore, we show that the biocompatibility and bone cell proliferation ability of the hydrogels can be improved through a mineralization process despite an observed reduction in breakage strain and stress. Taken as a whole, our work paves the way for the design of strong and tough hydrogels, with potential applications within biomedicine and particularly tissue engineering.

Synergistic Effect of PVDF-Coated PCL-TCP Scaffolds and Pulsed Electromagnetic Field on Osteogenesis.

Bone exhibits piezoelectric properties. Thus, electrical stimulations such as pulsed electromagnetic fields (PEMFs) and stimuli-responsive piezoelectric properties of scaffolds have been investigated separately to evaluate their efficacy in supporting osteogenesis. However, current understanding of cells responding under the combined influence of PEMF and piezoelectric properties in scaffolds is still lacking. Therefore, in this study, we fabricated piezoelectric scaffolds by functionalization of polycaprolactone-tricalcium phosphate (PCL-TCP) films with a polyvinylidene fluoride (PVDF) coating that is self-polarized by a modified breath-figure technique. The osteoinductive properties of these PVDF-coated PCL-TCP films on MC3T3-E1 cells were studied under the stimulation of PEMF. Piezoelectric and ferroelectric characterization demonstrated that scaffolds with piezoelectric coefficient d33 = -1.2 pC/N were obtained at a powder dissolution temperature of 100 °C and coating relative humidity (RH) of 56%. DNA quantification showed that cell proliferation was significantly enhanced by PEMF as low as 0.6 mT and 50 Hz. Hydroxyapatite staining showed that cell mineralization was significantly enhanced by incorporation of PVDF coating. Gene expression study showed that the combination of PEMF and PVDF coating promoted late osteogenic gene expression marker most significantly. Collectively, our results suggest that the synergistic effects of PEMF and piezoelectric scaffolds on osteogenesis provide a promising alternative strategy for electrically augmented osteoinduction. The piezoelectric response of PVDF by PEMF, which could provide mechanical strain, is particularly interesting as it could deliver local mechanical stimulation to osteogenic cells using PEMF.

Self-Assembled Nanofibrous Marine Collagen Matrix Accelerates Healing of Full-Thickness Wounds.

There is an urgent clinical need for wound dressings to treat skin injuries, particularly full-thickness wounds caused by acute and chronic wounds. Marine collagen has emerged as an attractive and safer alternative due to its biocompatibility, diversity, and sustainability. It has minimum risk of zoonotic diseases and less religious constraints as compared to mammalian collagen. In this study, we reported the development of a self-assembled nanofibrous barramundi (Lates calcarifer) collagen matrix (Nano-BCM), which showed good biocompatibility for full-thickness wound-healing applications. The collagen was extracted and purified from barramundi scales and skin. Thereafter, the physicochemical properties of collagen were systematically evaluated. The process to extract barramundi skin collagen (BC) gave an excellent 45% yield and superior purity (∼100%). More importantly, BC demonstrated structural integrity, native triple helix structure, and good thermal stability. BC demonstrated its efficacy in promoting human primary dermal fibroblast (HDF) and immortalized human keratinocytes (HaCaT) proliferation and migration. Nano-BCM has been prepared via self-assembly of collagen molecules in physiological conditions, which resembled the native extracellular matrix (ECM). The clinical therapeutic efficacy of the Nano-BCM was further evaluated in a full-thickness splinted skin wound mice model. In comparison to a clinically used wound dressing (DuoDerm), the Nano-BCM demonstrated significantly accelerated wound closure and re-epithelization. Moreover, Nano-BCM nanofibrous architecture and its ability to facilitate early inflammatory response significantly promoted angiogenesis and differentiated myofibroblast, leading to enhanced wound healing. Consequently, Nano-BCM demonstrates great potential as an economical and effective nonmammalian substitute to achieve skin regeneration.