Overview
The aim of this project is to create a multi-functional dressing that uses the microneedle patch (MN) and fusion protein in order to achieve effective detection of S. aureus and inhibit bacterial protein synthesis. Therefore, microneedle system plays an important role that is, the applicator, making AMPC more efficient and convenient to use in real life.
Fig.1 The appearance of microneedles
Fig.2 The MN size about 2.3*1.1 cm^2
Design of Microneedle Patch
How we Design ur Microneedle Patch?
We tried hard to make the ideal microneedles. Fig.3 fully delivered that we followed the engineering cycle to design, redesign, build, test and learn.
Fig.3 Handwritten design of microneedle patch(Click ☝ )
Abstract
Nowadays, there are many types of microneedles, such as hollow, solid, coated solid, dissolving, and hydrogel MNs. Considering the cost, function, and feasibility of operation in the laboratory, we chose to dissolve MNs for this project. (See the Protocol page to know how to fabricate the MNs.)
See Protocol page for detail information.
During the design process, we paid attention to the appearance, shape of the needle tips, overall structure, and materials. After many tests and continuous brainstorming among the members, it can be summarized into three generations. The following will describe them one by one. The second generation is the final version of the project. In addition, the last generation is limited by resources and technical difficulties, we let it be the prospective work. For details, please refer to Implementation.
Fig.4a The first generation(☝)
Fig.4a The second generation(☝)
Fig.4a The prospective MNs(☝)
First Generation
Our goal is to apply to the human body, so the needle tip must be biocompatible while avoiding the needle tip breaking in the skin and being sharp enough to penetrate the skin. Therefore, enough mechanical strength and penetration ability are necessary. After searching the literature and selecting the material specificity, we finally decided to use PLGA or gelatin as the needle tip material, which has biocompatibility, enough mechanical strength, and the ability to penetrate the epidermis.
Second Generation (Final type)
After the actual experimental test, we found that PLGA and gelatin hydrophilic properties can be released quickly in the human body, so we added the shell can protect the filler. According to the characteristics of S. aureus, we spotted that S. aureus secretes hyaluronidase, which is the extracellular enzyme, which can hydrolyze the hyaluronic acid (HA). So we use photo-cross-linkable hyaluronic acid methacrylate (HAMA) to be the shell material, so only encountering the bacteria that can secrete hyaluronidase, like S. aureus, triggering microneedles to release the drug. Finally, we chose gelatin, which is easier to obtain, as a filler and coated HAMA on the tips surface as our final solution.
The design of the shell brings many benefits:
- Strengthen the tips.
- Protect the filler which contains the drug.
- Using different materials to achieve the effect of selective drug delivery.
Fig.5 The HAMA coated microneedle
The Hyaluronidase Cleavage Mechanism
It is important to say that photo-cross-linkable hyaluronic acid methacrylate (HAMA) is the first stage to be degraded by Hyaluronidase from S. aureus. Herein, we set a selective stage to develop a microneedle that can detect bacteria and deliver drugs to the wound.
Fig.6 The hyaluronidase cleavage mechanism
Conclusion
The second-generation microneedle patch is our final design in this project. We developed a simple, rapid, and safe prototype wound dressing for a small-area skin infection that can detect bacteria and deliver drugs to the wound.
Experimental Tests of Microneedles
We have fabricated many microneedles in the laboratory. To confirm its feasibility, we did many tests, including material characteristic analysis, scanning electron microscope morphological images, dye release, practical tests on the bacteriaum and pigskin, etc.
Fig.7 The magnification image of microneedle
See Result - Microneedle page for detail information.
Prospective
Silk fibroin is an advanced biomaterial with biocompatibility, mechanical strength, and penetrate ability. It is extracted from cocoons and is a natural biological material that is often used in medical and aesthetic products. In material properties, compared with the PLGA and gelatin, silk protein has a larger molecular size, porous structure, and also more hydrophobic domains. It isn't easy to be quickly degraded and can achieve the effect of slow release. In addition, the molecular weight of AMPC is about 25~40kDa, so we need to enlarge the pores by means of salting out, freeze-drying, or gas foaming so that AMPC can be released through the pores successfully. In the future, we hope to add a chamber for storing medicines, so that the entire microneedle can be turned into a portable storage device, reducing the frequency of dressing changes and improving the convenience for users.
See Implementation page for detail information.
Bringing Our Microneedle to Real Life
As microneedle array progress to commercialization:
- We did the outer design for the microneedle patches as the product.
- Packaging microneedle patch by plastic case and retort pouch to protect our product from external damage, sun exposure, and oxidative deterioration.
- In the packaging box, attach an instruction and other accessories in the box, including a band-aid, an alcohol pad for users.
See Implementation page for detail information.
Fig.8 Outer packaging design