# Multi-tissue type condensations for trachea tissue regeneration via individual cell bioprinting

> **NIH VA I01** · JESSE BROWN VA MEDICAL CENTER · 2024 · —

## Abstract

Abstract
As a result of prolonged intubation, tracheostomy, external trauma, penetrating fragment projectiles, gunshot
wounds and improvised explosive devices during combat, and benign or malignant tumors, many soldiers and
veterans in the US military suffer from severe trachea stenosis or damage that can cause complete airway failure,
Since there is no successful long-term treatment for long-segment tracheal stenosis or damage, tissue
engineering strategies have been explored to develop neotracheas using different combinations of biomaterials
and cell sources. However, biomaterial scaffold-based approaches often interfere with critical cell-cell
interactions, cell proliferation and new extracellular matrix production that are important during the formation of
functional trachea tissue. A functional replacement trachea must retain (1) radial rigidity to prevent restenosis,
(2) anastomose with host vasculature to adequately provide nutrients to the implant, and (3) contain respiratory
epithelium to provide a protective mucosal layer. Combining three-dimensional (3D) bioprinting technologies with
scaffold-free tissue engineering principles presents a powerful platform for engineering a multi-tissue functional
trachea, and would circumvent the aforementioned limitations of scaffold-based approaches. This proposal aims
to leverage the benefits of our recently developed individual cell-only 3D bioprinting technology, which allows for
printing of complex and high-resolution cell condensation-based tissue constructs to engineer functional
tracheas. We plan to print scaffold-free, multi-tissue neotracheas using multiple discrete individual cell-only
bioinks for spatially distinct differentiation of tissue types driven by spatially controlled presentation of tissue-
specific growth factors. Construct self-assembly will be driven by the condensation of autologously sourced
human mesenchymal stem cells (hMSCs) for cartilaginous tissue and autologous endothelial progenitor cells
and hMSCs for prevascular tissue, with autologous human bronchial epithelial cells applied to line the lumen of
the neotrachea. Specifically, this proposal aims to (1) examine the role of the physical properties of the microgel
support slurry on cell-only bioink printing, condensation formation/maintenance, and chondrogenesis of the 3D
bioprinted structures, (2) 3D bioprint cartilage ring constructs with chondrogenic bioink and prevascularized ring
constructs with vasculogenic bioink using the individual cell-only bioprinting technology, and (3) engineer
prevascularized and epithelized tracheal tissue with chondrogenic and vasculogenic bioinks using the individual
cell-only bioprinting technology. As an exploratory aim, the capacity of the engineered tracheas to restore airway
functionality will be evaluated in an animal defect model. This work ultimately seeks to utilize a facile and flexible
individual cell-only bioink 3D printing platform to engineer a patient-specific replacement...

## Key facts

- **NIH application ID:** 10834107
- **Project number:** 5I01RX004288-02
- **Recipient organization:** JESSE BROWN VA MEDICAL CENTER
- **Principal Investigator:** Eben Alsberg
- **Activity code:** I01 (R01, R21, SBIR, etc.)
- **Funding institute:** VA
- **Fiscal year:** 2024
- **Award amount:** —
- **Award type:** 5
- **Project period:** 2023-05-01 → 2027-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10834107

## Citation

> US National Institutes of Health, RePORTER application 10834107, Multi-tissue type condensations for trachea tissue regeneration via individual cell bioprinting (5I01RX004288-02). Retrieved via AI Analytics 2026-05-29 from https://api.ai-analytics.org/grant/nih/10834107. Licensed CC0.

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