At present, dynamic wound closure processing under special circumstances is still difficult. Direct suturing can easily cause the wound to tear, leading to fluid leakage and the risk of accidents. Based on the excellent properties of adhesive hydrogels , some progress has been made in using them for wound sealing, but existing tissue adhesive hydrogels are too soft and stretchable to hold the wound edges together under dynamic loads . To this end, Li Zhe’s team from Sun Yat-sen University designed a gradient modulus tissue adhesive composite material for dynamic wound closure. Adhesives mainly consist of three functional components, an adhesive hydrogel matrix for wound sealing, a biodegradable micromesh with gradient modulus to prevent tearing, and an oil-infused surface for anti-adhesion (Figure 1). The patch in the dry state of is in the form of a flexible film (approximately 100 µm thick), which can be directly applied to uneven surfaces to achieve the function of closing wounds. The research results related to were published in "Advanced Functional Materials" on September 1, 2022 under the title "Gradient Modulus Tissue Adhesive Composite for Dynamic Wound Closure".
Figure 1 Gradient modulus tissue adhesive composite
Biodegradable polycaprolactone (PCL) micromesh with gradient modulus is first prepared and placed on a substrate coated with a thin layer of silicone oil . The silicone oil will partially penetrate into the micromesh and form a dip. oil surface; subsequently, the tissue adhesive pregel solution (prepared from gelatin and polyacrylic acid grafted with methacrylic acid gelatin cross-linked N-hydroxysuccinimide ester (PAAc-NHS)) was poured onto the micromesh placed in the mold. Penetrate into the porous micromesh until the surface where the oil is injected. After curing under UV irradiation, the PAAc-NHS network entangled with gelatin chains will become topologically entangled with PCL micronetworks, producing tissue adhesive composites with Janus adhesive properties.
- Characteristics of tissue adhesive composites
The authors used a novel angle solution blowing (A-SBS) method to prepare PCL biodegradable micronets (Figure 2a); due to the unique aerodynamics caused by the corner collector, the microfibers will be pulled laterally along the inclined surface by the high-pressure airflow, generating fiber micronets on the corner collector (Figure 2b). In particular, facilitates the generation of gradient modulus by adjusting the angle. A larger modulus in the middle can help avoid the wound tearing under load like a virtual suture, while a smaller modulus in the periphery will help create a tight interface with the underlying tissue without stress concentrations coupling. Therefore, the authors chose microgrids prepared on a 30° collector as a modular component for preparing tissue adhesives.
Figure 2 Preparation of gradient modulus tissue adhesive composite
- Adhesion test of tissue adhesive
Next, the authors characterized the gradient modulus properties of the patch, as shown in the stress-strain curve in Figure 3a. At the same time, a gradient modulus tissue adhesive composite was successfully prepared using the micromesh as the skeleton (Figure 3b). The modulus range can be adjusted by adding different layers of modular micro-networks to the tissue adhesive to apply to different tissue surfaces . Therefore, this design provides an effective strategy for fabricating gradient modulus tissue adhesive composites with good controllability. Furthermore, the adhesive material can adhere firmly to wet tissue surfaces for wound closure (Fig. 3c). The authors further compared the Young's modulus of the tissue adhesive with the moduli of different tissues/organs reported in the literature to fully demonstrate its reasonable applicability.
Figure 3 GmTAC for wound closure and prevention of tearing
- Biosafety of tissue adhesives
After the authors confirmed that the adhesive has Janus adhesion properties in vitro (Figure 4a), they further conducted an in vivo Janus adhesion test on anesthetized rabbits. Similar to in vitro observations, adhesives designed with anti-adhesion surfaces effectively prevent adhesion to surrounding tissues (Fig. 4b) . Based on the appropriate mechanical properties of the adhesive, it can be applied to various tissue surfaces (including intestines, stomach, lungs and heart, etc.) .At the same time, the adhesive material also has good biocompatibility and degradable properties.
Figure 4 Adhesion, safety, and biodegradability
- Dynamic simulation of tissue adhesives
To further validate the efficacy of the adhesive in wound closure and tear prevention, in vivo testing was performed while simulating the tension or expansion experienced by wounds in dynamic and fluid-rich environments. Overall, stress originating from the peripheral deformation of the adhesive matrix will be transferred to the topologically entangled micromesh skeleton. Due to the gradient modulus design, the adhesive patch at the proximal end of the incision will have a higher stress than the underlying tissue, producing a stress shielding effect with minimal stress concentration, which can effectively protect the wound from dynamic tearing and promote wound healing.
Figure 5 Simulating dynamic wound closure
In summary, This article prepared a gradient modulus tissue adhesive composite material through reasonable design and construction. The adhesive material is mainly prepared from three functional components, namely a viscous hydrogel matrix, a biodegradable micronet with gradient modulus and an oil-injected surface for anti-adhesion . A tissue adhesive patch that combines these features can simultaneously achieve strong adhesion to wet tissue surfaces, protect the wound from dynamic tearing, and prevent adhesion to surrounding tissue. In addition, patches designed with biodegradable materials can degrade over time under physiological conditions without the need to re-operate . These characteristics have been validated in vitro and in vivo through simulations, and this strategy provides an effective strategy and solution for managing dynamic wound closure.
Article source: https://doi.org/10.1002/adfm.202207306.
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