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Evaluation of an Engineered Hybrid Matrix for Bone Regeneration via Endochondral Ossification

  • Bioengineering and Enabling Technologies
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Abstract

Despite its regenerative ability, long and segmental bone defect repair remains a significant orthopedic challenge. Conventional tissue engineering efforts induce bone formation through intramembranous ossification (IO) which limits vascular formation and leads to poor bone regeneration. To overcome this challenge, a novel hybrid matrix comprised of a load-bearing polymer template and a gel phase is designed and assessed for bone regeneration. Our previous studies developed a synthetic ECM, hyaluronan (HA)–fibrin (FB), that is able to mimic cartilage-mediated bone formation in vitro. In this study, the well-characterized HA–FB hydrogel is combined with a biodegradable polymer template to form a hybrid matrix. In vitro evaluation of the matrix showed cartilage template formation, cell recruitment and recruited cell osteogenesis, essential stages in endochondral ossification. A transgenic reporter-mouse critical-defect model was used to evaluate the bone healing potential of the hybrid matrix in vivo. The results demonstrated host cell recruitment into the hybrid matrix that led to new bone formation and subsequent remodeling of the mineralization. Overall, the study developed and evaluated a novel load-bearing graft system for bone regeneration via endochondral ossification.

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Acknowledgment

The authors acknowledge funding from NSF EFRI (#1332329) and NSF EFMA (#1640008). Dr. Nukavarapu also acknowledges support from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (#R01EB020640).

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Authors and Affiliations

  1. Department of Materials Science, & Engineering, University of Connecticut, Storrs, CT, 06269, USA

    Paiyz E. Mikael & Syam P. Nukavarapu

  2. Department of Biomedical Engineering, University of Connecticut, 260 Glenbrook Road, Unit 3247, Storrs, CT, 06269, USA

    Aleksandra A. Golebiowska & Syam P. Nukavarapu

  3. Center for Regenerative Medicine and Skeletal Development, University of Connecticut Health, Farmington, CT, 06032, USA

    Xiaonan Xin & David W. Rowe

  4. Department of Orthopaedic Surgery, University of Connecticut Health, Farmington, CT, 06032, USA

    Syam P. Nukavarapu

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  1. Paiyz E. Mikael
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  2. Aleksandra A. Golebiowska
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  3. Xiaonan Xin
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  4. David W. Rowe
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  5. Syam P. Nukavarapu
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Correspondence to Syam P. Nukavarapu.

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Associate Editor Jane Grande-Allen oversaw the review of this article.

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Mikael, P.E., Golebiowska, A.A., Xin, X. et al. Evaluation of an Engineered Hybrid Matrix for Bone Regeneration via Endochondral Ossification. Ann Biomed Eng 48, 992–1005 (2020). https://doi.org/10.1007/s10439-019-02279-0

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