# Small RNA-Modulated Exosome Mimetics For Craniofacial Regeneration

> **NIH NIH R03** · UNIVERSITY OF MARYLAND EASTERN SHORE · 2022 · $133,126

## Abstract

Abstract
Large craniofacial defects remain an extraordinary challenge to clinical surgical reconstruction. Conventional
approaches of auto/allografting for clinical craniofacial reconstruction are significantly compromised by
availability and donor-site morbidity. Mesenchymal stem cells (MSCs) with multipotency are increasingly
employed as a cell-based approach for skeletal regeneration. Nonetheless, accumulative evidences suggest
that contribution of MSCs to regenerated tissues is limited while stimulation of local healing processes through
paracrine secretion exerts more important roles. MSC-derived extracellular vesicles (EVs) have shown
regenerative potency in varying animal models and displayed therapeutic advantages like intrinsic homing
effect, stability, low immunogenicity and effective signaling stimulation. However, the widespread use of
exosome-mediated treatment still requires the significant improvement of production yield and regenerative
ability. Developing a scalable approach like generation of exosome mimetics (EMs) with substantial yields has
been investigated in previous studies. Additionally, exosome-mediated cargo of exogenous therapeutic factors
like siRNAs has been conducted to improve its regenerative capability. The exogenous transport of these
factors is also growing concerns of high cost, poor pharmacokinetics and inefficiency. Herein, the
augmentation of intrinsic inductive/therapeutic molecules within exosomes exhibits a promising therapeutic
strategy. Skeletal cells secrete important growth factors like BMP2, which incite osteoblastic commitment of
skeletal progenitor cells and subsequent mineral deposition. In response to BMP stimulus, MSCs or
osteoblasts elevate BMP antagonist like noggin, suggesting a negative feedback to prevent overexposure of
BMP signaling. Introduction of exogenous noggin was revealed to impair cranial formation while inhibition of
endogenous noggin promoted cranial regeneration by activating endogenous BMP signaling. These
observations highlight the potency of noggin suppression on up-regulation of endogenous BMP activity and
subsequent osseous deposition. In our preliminary studies, EMs were generated from MSCs via a distinctive
extrusion approach, demonstrating high yields of exosomes with apparent osteogenic induction. Moreover,
EMs obtained from noggin-suppression MSCs (EM-NG) revealed the elevated noggin siRNA and osteogenic
potency. Together, we hypothesize that EM-NG could enhance osteoblastic commitment of endogenous
skeletal stem cells (SSCs) and craniofacial regeneration. Two specific aims are proposed to investigate this
hypothesis: 1) To investigate the effect of EM-NG on endogenous cranial SSCs and bone healing; 2) To
examine the implant of EM-NG-laden scaffold for restoration of segmental mandibular defects. The
completion of this proposal will offer significant foundation to further develop effective cell-free approaches for
clinical craniofacial defect repair. The additional r...

## Key facts

- **NIH application ID:** 10741983
- **Project number:** 7R03DE030539-03
- **Recipient organization:** UNIVERSITY OF MARYLAND EASTERN SHORE
- **Principal Investigator:** Jiabing Fan
- **Activity code:** R03 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $133,126
- **Award type:** 7
- **Project period:** 2022-11-29 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10741983

## Citation

> US National Institutes of Health, RePORTER application 10741983, Small RNA-Modulated Exosome Mimetics For Craniofacial Regeneration (7R03DE030539-03). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10741983. Licensed CC0.

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