The Foreign Body Response to an Implantable Therapeutic Reservoir in a Diabetic Rodent Model

Beatty, Rachel; Lu, Chuan-En; Marzi, Julia; Levey, Ruth E.; Berrio, Daniel Carvajal; Lattanzi, Giulia; Wylie, Robert B.; O'Connor, Raymond G.; Wallace, Eimear; Ghersi, Giulio; Salamone, Monica; Duffy, Garry P.; Layland, Shannon L.; Schenke‐Layland, Katja

doi:10.1089/ten.tec.2021.0163

Cited by 9 publications

(15 citation statements)

References 73 publications

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“…The capsular region (Fig. 3C) directly beneath the dome of the device and overlying membrane was reconstructed using segmentation (Mimics, Materialise, Leuven) from micro-computed tomography (micro-CT) ( 1 , 35 ). A time-dependent increase in mean capsular thickness (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…Previous studies have noted that the fibrotic capsule continues to mature and develop for months after implantation, with the permeability decreasing as the capsule becomes denser, further inhibiting drug release ( 18 ). To determine an actuation regimen that can overcome a more developed fibrotic capsule, capsular porosity was determined using histological analysis of samples from previous work ( 18 , 35 ) at days 28 and 58 (similarities in fibrotic capsules validated across rodent species and sex; table S11 and fig. S9).…”

Section: Discussionmentioning

confidence: 99%

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Soft robot–mediated autonomous adaptation to fibrotic capsule formation for improved drug delivery

Beatty,

Mendez,

Schreiber

et al. 2023

Sci. Robot.

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The foreign body response impedes the function and longevity of implantable drug delivery devices. As a dense fibrotic capsule forms, integration of the device with the host tissue becomes compromised, ultimately resulting in device seclusion and treatment failure. We present FibroSensing Dynamic Soft Reservoir (FSDSR), an implantable drug delivery device capable of monitoring fibrotic capsule formation and overcoming its effects via soft robotic actuations. Occlusion of the FSDSR porous membrane was monitored over 7 days in a rodent model using electrochemical impedance spectroscopy. The electrical resistance of the fibrotic capsule correlated to its increase in thickness and volume. Our FibroSensing membrane showed great sensitivity in detecting changes at the abiotic/biotic interface, such as collagen deposition and myofibroblast proliferation. The potential of the FSDSR to overcome fibrotic capsule formation and maintain constant drug dosing over time was demonstrated in silico and in vitro. Controlled closed loop release of methylene blue into agarose gels (with a comparable fold change in permeability relating to 7 and 28 days in vivo) was achieved by adjusting the magnitude and frequency of pneumatic actuations after impedance measurements by the FibroSensing membrane. By sensing fibrotic capsule formation in vivo, the FSDSR will be capable of probing and adapting to the foreign body response through dynamic actuation changes. Informed by real-time sensor signals, this device offers the potential for long-term efficacy and sustained drug dosing, even in the setting of fibrotic capsule formation.

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Section: Resultsmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Soft robot–mediated autonomous adaptation to fibrotic capsule formation for improved drug delivery

Beatty,

Mendez,

Schreiber

et al. 2023

Sci. Robot.

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“…Additionally, patient comfort is an important consideration with devices of this size and shape and this metric would need to be tested in a clinical trial setting. This material also has excellent manufacturing flexibility where reservoir shape, size and volume can be easily modified [ 51 , 52 , 54 , 55 ]. Additionally, an inner support structure can be easily added to support dispersion of the islets throughout the device and prevent islet clumping [ 51 , 56 , 57 ].…”

Section: Discussionmentioning

confidence: 99%

Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices

McDermott

Robinson

Holcombe

et al. 2021

J. R. Soc. Interface.

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Delivering a clinically impactful cell number is a major design challenge for cell macroencapsulation devices for Type 1 diabetes. It is important to understand the transplant site anatomy to design a device that is practical and that can achieve a sufficient cell dose. We identify the posterior rectus sheath plane as a potential implant site as it is easily accessible, can facilitate longitudinal monitoring of transplants, and can provide nutritive support for cell survival. We have investigated this space using morphomics across a representative patient cohort (642 participants) and have analysed the data in terms of gender, age and BMI. We used a shape optimization process to maximize the volume and identified that elliptical devices achieve a clinically impactful cell dose while meeting device manufacture and delivery requirements. This morphomics framework has the potential to significantly influence the design of future macroencapsulation devices to better suit the needs of patients.

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“… Co-transplantation of Fas ligand with streptavidin (SA-FasL) microgels and islets [490] . Robotic drug delivery technique Dynamic Soft Reservoir (DSR) that utilized mechanical oscillation to mitigate fibrotic capsule formation [224] , [491] . …”

Section: Current State Of Islet Transplantationmentioning

confidence: 99%

“…Dynamic Soft Reservoir (DSR) that utilized mechanical oscillation to mitigate fibrotic capsule formation [224] , [491] .…”

Section: Current State Of Islet Transplantationmentioning

confidence: 99%

Type 1 diabetes and engineering enhanced islet transplantation

Jeyagaran

Lu²,

Zbinden³

et al. 2022

Advanced Drug Delivery Reviews

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The Foreign Body Response to an Implantable Therapeutic Reservoir in a Diabetic Rodent Model

Cited by 9 publications

References 73 publications

Soft robot–mediated autonomous adaptation to fibrotic capsule formation for improved drug delivery

Soft robot–mediated autonomous adaptation to fibrotic capsule formation for improved drug delivery

Developing a morphomics framework to optimize implant site-specific design parameters for islet macroencapsulation devices

Type 1 diabetes and engineering enhanced islet transplantation

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