# Engineering structural bone allografts for enhanced repair and reconstruction

> **NIH NIH R21** · UNIVERSITY OF ROCHESTER · 2020 · $168,575

## Abstract

PROJECT SUMMARY
Bone grafting procedures number over 500,000 annually in the United States, with allograft
tissues used for 33% of the bone grafting operations. Although bone allografts from cadavers
and donors have been utilized extensively to repair bone defects, bone allografts have not
achieved the similar level of efficacy as compared with bone autografts. Furthermore, bone
allografts for treatment of critical-sized bone defects show extremely slow engraftment and ≈
60% long-term failure rates due to fibrotic nonunions, poor vascularization, poor
osteointegration, infections, and microcrack propagation. To improve the healing and
integration, strategies have been developed to modify bone allografts to enhance their
osteogenic and angiogenic properties. These strategies include coating with polymers with and
without incorporation of different drugs, coating with adeno-associated virus – bone
morphogenetic protein 2 (AAV-BMP2) vectors, coating with hydrogels containing bone marrow
stem cells (BMSCs), wrapping with BMSCs-seeded nanofiber membranes. However, these
strategies are associated with many problems including i) fibrosis tissue formation, ii)
involvement of living cells, iii) uneven callus formation, and iv) safety of virus vectors. Therefore,
there is an urgent need to engineer off-the-shelf bone allografts to improve their efficacy and
performance in repair of the critical-sized bone defects. The primary objective of this study is to
engineer bone allografts with a novel coating capable of releasing anti-fibrotic agents and bone
growth regulating factors in either simultaneous or sequential fashion to improve the healing and
osteointegration. To test the hypothesis and accomplish the primary objective, our strategy
includes: i) Establish a method of engineering bone allograft with incorporation of BMP-2
peptides and a TGF-β signaling inhibitor to the coatings; and ii) Assess the anti-fibrotic efficacy,
new bone formation, and osseointegration of engineered bone allografts in a murine femoral
defect model; and 3) Examine the antagonism between TGF-β and BMP-2 signaling during
bone allograft repair. We expect to identify the role of anti-fibrotic agents and bone growth
regulatory factors on the healing of a critical bone defect through surface engineered bone
allografts. The proposed strategy could also be useful in various applications aimed at
promoting tissue regeneration.

## Key facts

- **NIH application ID:** 9978190
- **Project number:** 1R21AR076056-01A1
- **Recipient organization:** UNIVERSITY OF ROCHESTER
- **Principal Investigator:** Jingwei Xie
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $168,575
- **Award type:** 1
- **Project period:** 2020-04-17 → 2022-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9978190

## Citation

> US National Institutes of Health, RePORTER application 9978190, Engineering structural bone allografts for enhanced repair and reconstruction (1R21AR076056-01A1). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9978190. Licensed CC0.

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