Dynamic actuation enhances transport and extends therapeutic lifespan in an implantable drug delivery platform.
Ellen T RocheDebkalpa GoswamiSophie X WangYiling FanNiamh A WardRuth E LeveyRachel BeattyScott T RobinsonDeclan SheppardRaymond O'ConnorDavid S MonahanLesley TraskKeegan L MendezClaudia E VarelaMarkus A HorvathRobert WylieJoanne O'DwyerDaniel A Domingo-LopezArielle S RothmanGarry P DuffyEimear B DolanEllen T RochePublished in: Nature communications (2022)
Fibrous capsule (FC) formation, secondary to the foreign body response (FBR), impedes molecular transport and is detrimental to the long-term efficacy of implantable drug delivery devices, especially when tunable, temporal control is necessary. We report the development of an implantable mechanotherapeutic drug delivery platform to mitigate and overcome this host immune response using two distinct, yet synergistic soft robotic strategies. Firstly, daily intermittent actuation (cycling at 1 Hz for 5 minutes every 12 hours) preserves long-term, rapid delivery of a model drug (insulin) over 8 weeks of implantation, by mediating local immunomodulation of the cellular FBR and inducing multiphasic temporal FC changes. Secondly, actuation-mediated rapid release of therapy can enhance mass transport and therapeutic effect with tunable, temporal control. In a step towards clinical translation, we utilise a minimally invasive percutaneous approach to implant a scaled-up device in a human cadaveric model. Our soft actuatable platform has potential clinical utility for a variety of indications where transport is affected by fibrosis, such as the management of type 1 diabetes.
Keyphrases
- drug delivery
- minimally invasive
- cancer therapy
- immune response
- high throughput
- endothelial cells
- ultrasound guided
- high intensity
- physical activity
- emergency department
- robot assisted
- mesenchymal stem cells
- adipose tissue
- toll like receptor
- climate change
- cell therapy
- bone marrow
- weight loss
- liver fibrosis
- adverse drug
- pluripotent stem cells