# Development of bio-integrated devices to enhance transplant survival for subcutaneous encapsulated cell therapies

> **NIH NIH K99** · MASSACHUSETTS INSTITUTE OF TECHNOLOGY · 2022 · $87,682

## Abstract

Encapsulated cell therapies (ECT) are attractive therapeutic platforms that involve the housing
of collections of transplanted cells capable of secreting therapeutic proteins within polymeric
frames. These technologies represent the potential to eliminate patient dependence on complex
drug-dosing regimens while maintaining circulating drug levels within healthy, nontoxic
therapeutic ranges for diseases ranging from autoimmune disorders to cancer. Transplanted
cells are isolated from host immune systems via encapsulation materials and semipermeable,
porous polymeric membranes (immunisolation membranes) via size exclusion effects. Despite
attracting significant interest, ECT devices have not found widespread clinical translation owing
to transplant failure, with low oxygen tension within the transplanted cell microenvironment and
fibrosis representing major causes. Size considerations related to cellular packing density
represent a further translational challenge. This challenge is particularly acute in subcutaneous
(SC) implants owing to the region’s low vascularization and high rates of fibrotic capsule
formation. Despite these hurdles, SC implants have attracted considerable attention owing to
the minimally invasive surgery requirements and potential for easy device monitoring and
retrieval. In this proposal, I will use approaches in microfabrication and bioelectronic device
design to improve oxygen tension within the transplanted cell microenvironment in SC-ECT
devices. In Aim 1 I will develop advanced multiphysics models to predict and address oxygen
need in implanted SC devices. In Aim 2, I will use surface chemical modifications to suppress
fibrosis and ensure long-term transplant survival in oxygen-generating bioelectronic ECT
implants. In Aim 3, I will pursue system level integration using design principles in flexible
bioelectronics, biosensor development and resonant inductive wireless power transfer
approaches. If successful, the resulting platform technology will support SC transplanted cell
survival long term, with potential applications across cell types and disease models. The work is
highly interdisciplinary, incorporating materials science, cell therapies, drug delivery and
electronic/electrical engineering. If successful, the work will create a platform technology
capable of addressing a wide range of unmet therapeutic needs in minimally invasive
implantation sites to de-risk clinical translation. My background is primarily in the physical
sciences: through this Fellowship, I will work closely with my co-mentors, Profs. Daniel
Anderson and Robert Langer at MIT to develop skills that will allow me to work at the interface
between engineering and the life sciences, with a focus on clinical translation.

## Key facts

- **NIH application ID:** 10525644
- **Project number:** 1K99EB032427-01A1
- **Recipient organization:** MASSACHUSETTS INSTITUTE OF TECHNOLOGY
- **Principal Investigator:** Siddharth Krishnan
- **Activity code:** K99 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $87,682
- **Award type:** 1
- **Project period:** 2022-06-15 → 2024-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10525644

## Citation

> US National Institutes of Health, RePORTER application 10525644, Development of bio-integrated devices to enhance transplant survival for subcutaneous encapsulated cell therapies (1K99EB032427-01A1). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10525644. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*