8. General discussion 211 8. studies with EPI-assisted treatments for other indications in which normally needles would be required, such as local anesthesia before local surgical procedures. Moreover, EPI-assisted treatment could be beneficial in the intralesional treatment of inflammatory diseases such as alopecia areata, lichen simplex, hidradenitis suppurativa, prurigo nodularis and common warts. Lastly, in the future there could be a place for the intralesional treatment with chemotherapeutics such as bleomycin or 5-fluorouracil, but also immunotherapy with checkpoint inhibitors such as anti-programmed cell death-1 therapy (aPD-1) or hedgehog inhibitors such as vismodegib to treat non-melanoma skin cancer.29-31 However, the evidence for intralesional treatment with these therapeutics in basal cell carcinoma and squamous cell carcinoma is currently limited, and therefore should only be considered if local excision is not an option, e.g. in elderly patients with multiple non-melanoma skin cancer lesions who do not wish further excisions. Indications for needle-free drug delivery beyond dermatology The advantages of needle-free drug delivery are not limited to the treatment of skin diseases. More than half of children and almost a quarter of the adult population fears needles.20 This is one of the reasons patients can be reluctant to receive vaccinations. For this reason, there is an urgent need for needle-free vaccination options. Suggestions for engineering improvements for next generation NFI devices As stated before, it is crucial that clinicians and engineers collaborate and synergize to develop even more effective, safe and patient-friendly next generation jet-injectors. In this thesis, we performed studies in an ex-vivo and in-vivo setting, enabling the exploration of issues of current EPIs. Firstly, we observed increased residue formation on the skin in both ex vivo and in vivo studies with keloid tissue, compared to previous research with ex vivo healthy skin samples. Therefore, we would suggest the addition of a system that can measure skin thickness and rigidity, which can regulate settings such as volume, pressure and jet-injection speed automatically based on a feedback system. Recently, there has been growing interest in EPIs that use laser energy. The first EPI, the Mirajet that is actuated by laser energy was commercialized in 2022.32 This mechanism
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