Wound healing concerns almost all bed-side related diseases. With our increasing comprehension of healing nature, the physical and chemical natures behind the wound microenvironment have been decoupled. Wound care demands timely screening and prompt diagnosis of wound complications such as infection and inflammation. Biosensor by the way of exhaustive collection, delivery, and analysis of data, becomes indispensable to arrive at an ideal healing upshot and controlling complications by capturing in-situ wound status. Electrochemical based sensors carry some potential unstable performance subjected to the electrical circuitry and power access and contamination. The colorimetric sensors are free from those concerns. We report that microsensors designed from O/W/O of capillary fluids can continuously monitor wound temperature, pH and glucose concentration. We combined three different types of microgels to encapsulate liquid crystals of cholesterol, nontoxic fuel litmus and two glucose-sensitizing enzymes. A smartphone applet was then developed to convert wound healing images to RGB of digitalizing data. The microgel dressing effectively demonstrates the local temperature change, pH and glucose levels of the wound in high resolution where a microgel is a 'pixel'. They are highly responsive, reversible and accurate. Monitoring multiple physicochemical and physiological indicators provides tremendous potential with insight into healing processing.
Nature makes the most beautiful solution to involuted problems. Among them, the parallel tubular structures are capable of transporting fluid quickly in plant trunks and leaf stems, which demonstrate an ingenious evolutionary design. This study develops a mini-thermoelectric semiconductor P–N module to create gradient and parallel channeled hydrogels. The modules decrease quickly the temperature of polymer solution from 20 °C to −20 °C within 5 min. In addition to the exceptional liquid absorption rate, the foams exhibited shape memory mechanics. Our mini device universally makes the inspired structure in such as chitosan, gelatin, alginate and polyvinyl alcohol. Non-compressible hemorrhages are the primary cause of death in emergency. The rapid liquid absorption leads to fast activation of coagulation, which provides an efficient strategy for hemostasis management. We demonstrated this by using our semiconductor modules on collagen-kaolin parallel channel foams with their high porosity (96.43%) and rapid expansion rate (2934%). They absorb liquid with 37.25 times of the own weight, show 46.5-fold liquid absorption speed and 24-fold of blood compared with random porous foams. These superior properties lead to strong hemostatic performance in vitro and in vivo.
Bacterial infections and antibiotic resistance represent significant global public health challenges, necessitating the development of innovative antibacterial agents with targeted delivery capabilities. Our study utilized macrophages’ natural ability to recognize bacteria and the increased reactive oxygen species (ROS) at infection sites to develop a novel nanoparticle for targeted delivery and controlled release. We prepared bacteria-activated macrophage membranes triggered by Staphylococcus aureus (Sa-MMs), which showed significantly higher expression of Toll-like receptors (TLRs), compared to normal macrophage membranes (MMs). These Sa-MMs were then used to coat vancomycin-loaded amphiphilic nanoparticles with ROS responsiveness (Van-NPs), resulting in the novel targeted delivery system Sa-MM@Van-NPs. Studies both In vitro and in vivo demonstrated that biocompatible Sa-MM@Van-NPs efficiently targeted infected sites and released vancomycin to eliminate bacteria, facilitating faster wound healing. By combining targeted delivery to infected sites and ROS-responsive antibiotic release, this approach might represent a robust strategy for precise infection eradication and enhanced wound healing.
Infection and vascular dysfunction are two major reasons for delayed wound healing, especially in the scenario of multidrug-resistant bacterial has been a challenge for antibiotics usage. Probiotics are effective in fighting pathogens, while avoiding the destruction of skin microbiome. However, the viability of probiotics is a major obstacle in clinical application. As a non-protein proangiogenic drug, deferoxamine (DFO) has significant advantages over traditional growth factors in terms of cost, storage and transportation conditions, and stability. However, there is still a problem of short half-life that requires reliable drug delivery carriers to maximize its effect. Here, we developed multiple-chambered microgels using electrospray and microfluidics. Lactobacillus fermentum (LF) and DFO, respectively, for the management of multidrug-resistant Pseudomonas aeruginosa (MPA) and promotion of wound healing. We first tested five probiotics isolated from healthy people and found LF inhibiting the growth of MPA by lowering local pH and antimicrobial substances. The multi-chambered microgels effectively inhibited MPA by delivering probiotics, they can also protect probiotics from antibiotics. DFO promoted the angiogenesis of human umbilical venous endothelial cells. The microgel system had good biocompatibility and hemocompatibility. In a MPA infected wound, the microgel system effectively alleviated wound infection by 87.44%, improved angiogenesis by 29.32% and accelerated wound healing. This work suggests that multi-compartmented microgels loaded with probiotics and deferoxamine have great potential in wounds with multidrug-resistant bacteria.
Negative pressure wound therapy (NPWT) offers significant advantages in terms of rate and time for healing through generating sub-vacuum to draw out inflammatory exudate and promote wound closure. However, continuous drainage probably leads to healing delay due to the lack of information about the real status of the wound bed and the potential risk of infection. To address this concern, printed Negative Pressure Smart Patch (NPSP) is reported by integrating smart real-time sensing acidity (infection) and glucose, and anti-infection into NPWT systems. In addition, NPSP delivers vancomycin through chitosan porous microspheres under negative pressure to modulate wound healing. Compared with NPWT, NPSP projects a promising approach to removing bacteria, reducing local inflammation, and accelerating healing in a short period of time.
Current hemostatic agents or dressings are not efficient under extremely hot and cold environments due to deterioration of active ingredients, water evaporation and ice crystal growth. To address these challenges, we engineered a biocompatible hemostatic system with thermoregulatory properties for harsh conditions by combining the asymmetric wetting nano-silica aerogel coated-gauze (AWNSA@G) with a layer-by-layer (LBL) structure. Our AWNSA@G was a dressing with a tunable wettability prepared by spraying the hydrophobic nano-silica aerogel onto the gauze from different distances. The hemostatic time and blood loss of the AWNSA@G were 5.1 and 6.9 times lower than normal gauze in rat's injured femoral artery model. Moreover, the modified gauze was torn off after hemostasis without rebleeding, approximately 23.8 times of peak peeling force lower than normal gauze. For the LBL structure, consisting of the nano-silica aerogel layer and a n-octadecane phase change material layer, in both hot (70 °C) and cold (-27 °C) environments, exhibited dual-functional thermal management and maintained a stable internal temperature. We further verified our composite presented superior blood coagulation effect in extreme environments due to the LBL structure, the pro-coagulant properties of nano-silica aerogel and unidirectional fluid pumping of AWNSA@G. Our work, therefore, shows great hemostasis potential under normal and extreme temperature environments.
Surgical sutures close wounds and promote healing. Sutures need to meet appropriate mechanical properties and biocompatibility, so complex and high-cost braiding processes have been developed for better mechanical properties. However, they still cannot work ideally in some scenarios, such as pain and infection. Pain is the most common symptom in almost all injuries, infections, and diseases. Inadequate management of pain leads to untoward physical and psychological outcomes in patients. For these purposes, we designed a multifunctional composite suture of micro silk fibroin fiber (SF). It was extracted in situ ultra-long and ultra-fine SFs where a single thread can reach hundreds of meters from a cocoon. The suture can adsorb anti-infection vancomycin by turning pH and then coated with methacrylated gelatin as a sheath to load a pain-killer ibuprofen (SMG-VC-IB). SMG-VC-IB can withstand a tension force of nearly 18 N, two times the Mersilk & REG; suture. SMG-VC-IB can maintain prolonged release for efficient pain management and anti-infection. We applied PET/CT to investigate objective metabolic data in brain regions and found that the pain-killer reached efficacy in our built pain model of quadriceps femoris incision in rats. We found SMG-VC-IB reduced metabolic levels in pain-related brain regions, including the classical pain matrix. It was also verified that the pain-killer ibuprofen from sutures helps to pass through the postoperative inflammatory period to a comfortable recovery period. Our research presented an ecofriendly manufacturing solution for designing multifunctional composite sutures for pain management and infection control.
Bioactive materials based on a nature-derived extracellular matrix (NECM) represent a category of biomedical devices with versatile therapeutic applications in the realms of tissue repair and engineering. With advancements in decellularization technique, the inherent bioactive molecules and the innate nano-structural and mechanical properties are preserved in three-dimensional scaffolds mainly composed of collagens. Techniques such as electrospinning, three-dimensional printing, and the intricate fabrication of hydrogels are developed to mimic the physical structures, biosignalling and mechanical cues of ECM. Until now, there has been no approach that can fully account for the multifaceted properties and diverse applications of NECM. In this review, we introduce the main proteins composing NECMs and explicate the importance of them when used as therapeutic devices in tissue repair. Nano-structural features of NECM and their applications regarding tissue repair are summarized. The origins, degradability, and mechanical property of and immune responses to NECM are also introduced. Furthermore, we review their applications, and clinical features thereof, in the repair of acute and chronic wounds, abdominal hernia, breast deformity, etc. Some typical marketed devices based on NECM, their indications, and clinical relevance are summarized.