# In situ bioprinting of high-density cell-laden core-shell microgel bioinks enabling cellular condensation for vascularized bone tissue regeneration

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

## Abstract

Abstract
Bone damage and loss resulting from combat associated penetrating fragment projectiles, gunshot wounds and
improvised explosive devices are some of the most common injuries US Military personnel experience and
contribute to increasing Veterans’ health care costs. Yet, there are few viable options to consistently regenerate
functional craniofacial bone for soldiers and veterans. Therefore, there is a significant need for the development
of innovative therapeutic approaches to address this problem. Cell-laden biomaterial scaffold-based strategies
face several challenges, such as limited cell-cell interactions, potential immune and/or inflammatory reaction,
and unsynchronized scaffold degradation rate with new tissue formation. Promising new scaffold-free cellular
condensation strategies can address these issues. To date, however, their formation has still required in vitro
culture prior to implantation. To overcome this issue, we have engineered a new technology: immediately
implantable, biodegradable and photocrosslinkable high-density hMSC-laden core-shell microgels enabling cell
condensations and subsequent generation of functional tissues in vivo without in vitro culture. Using this system
and 3D bioprinting, it is now possible to precisely engineer the architecture of osteogenic cell condensations for
bone regeneration to match patient-specific defects. Recently, we have also engineered technology capable of
3D printing an individual cell-only bioink and maintaining the printed structures. By using the in situ bioprinted
osteogenic core-shell microparticles as a support slurry bath, it is now possible to print defined 3D patterns of
prevascular individual cell-only bioink into the slurry to generate a tissue construct composed of osteogenic
hMSC condensations with an incorporated spatially patterned prevascular network of cell condensations. The
rapid degradation of the microgel hydrogel shell layer will enable fusion of the osteogenic condensations with
each other, the forming prevascular network and the surrounding host tissue. Locally delivered growth factor
from incorporated microparticles will drive the local formation of the two different tissue types to promote the
growth of functional vascularized bone tissue. We hypothesize that multi-tissue cell condensations can be
fabricated directly in vivo in complex architectures using osteogenic core-shell microgel and individual cell-based
prevasculogenic bioinks and 3D bioprinting technology to form patterned prevascularized bone constructs for
healing critical-sized cranial defects without in vitro processing and culturing. Specifically, we aim to (1) examine
the role of physical properties of the core-shell microgel bioink and printing parameters on the resolution and
shape fidelity of the 3D bioprinted constructs, (2) engineer and evaluate 3D bioprinted prevasculature patterned
high cell-density bone constructs, and (3) determine the preclinical potential of in situ 3D bioprinted
...

## Key facts

- **NIH application ID:** 10865842
- **Project number:** 1I01RX004825-01A1
- **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:** 1
- **Project period:** 2024-05-01 → 2028-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10865842

## Citation

> US National Institutes of Health, RePORTER application 10865842, In situ bioprinting of high-density cell-laden core-shell microgel bioinks enabling cellular condensation for vascularized bone tissue regeneration (1I01RX004825-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/10865842. Licensed CC0.

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