An alginate-based hybrid system for growth factor delivery in the functional repair of large bone defects

Kolambkar, Yash M.; Dupont, Kenneth M.; Boerckel, Joel D.; Huebsch, Nathaniel; Mooney, David J.; Hutmacher, Dietmar W.; Guldberg, Robert E.

Affiliations

¹Wallace H. Coulter Department of Biomedical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr, Atlanta, GA 30332, USA

²George W. Woodruff School of Mechanical Engineering, Parker H. Petit Institute for Bioengineering and Bioscience, Georgia Institute of Technology, 315 Ferst Dr, Atlanta, GA 30332, USA

³School of Engineering and Applied Sciences, Harvard-MIT Division of Health Sciences and Technology, Harvard University, 29 Oxford St., 319 Pierce Hall, USA

⁴School of Engineering and Applied Sciences, Wyss Institute for Biologically Inspired Engineering, Harvard University, 29 Oxford St., 319 Pierce Hall, USA

⁵Institute of Health and Biomedical Innovation, Queensland University of Technology, George W. Woodruff School of Mechanical Engineering, Georgia Institute of Technology, 60 Musk Avenue, Kelvin Grove QLD 4059, Australia

Abstract and keywords

The treatment of challenging fractures and large osseous defects presents a formidable problem for orthopaedic surgeons. Tissue engineering/regenerative medicine approaches seek to solve this problem by delivering osteogenic signals within scaffolding biomaterials. In this study, we introduce a hybrid growth factor delivery system that consists of an electrospun nanofiber mesh tube for guiding bone regeneration combined with peptide-modified alginate hydrogel injected inside the tube for sustained growth factor release. We tested the ability of this system to deliver recombinant bone morphogenetic protein-2 (rhBMP-2) for the repair of critically-sized segmental bone defects in a rat model. Longitudinal μ-CT analysis and torsional testing provided quantitative assessment of bone regeneration. Our results indicate that the hybrid delivery system resulted in consistent bony bridging of the challenging bone defects. However, in the absence of rhBMP-2, the use of nanofiber mesh tube and alginate did not result in substantial bone formation. Perforations in the nanofiber mesh accelerated the rhBMP-2 mediated bone repair, and resulted in functional restoration of the regenerated bone. μ-CT based angiography indicated that perforations did not significantly affect the revascularization of defects, suggesting that some other interaction with the tissue surrounding the defect such as improved infiltration of osteoprogenitor cells contributed to the observed differences in repair. Overall, our results indicate that the hybrid alginate/nanofiber mesh system is a promising growth factor delivery strategy for the repair of challenging bone injuries.

Keywords: Bone regeneration; Drug delivery; Bone morphogenetic protein; Scaffold; Nanofiber mesh; Alginate

Links

DOI: 10.1016/j.biomaterials.2010.08.074

PubMed: 20864165

WoS: 000285217600009

History

Received: 2010-08-18

Accepted: 2010-08-27

Online: 2010-09-22

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Cited By (23)

Year	Entry
2011	Boerckel JD, Kolambkar YM, Dupont KM, Uhrig BA, Phelps EA, Stevens HY, García AJ, Guldberg RE. Effects of protein dose and delivery system on BMP-mediated bone regeneration. Biomaterials. November 2011;32(22):5241-5251.
2011	Kolambkar YM, Boerckel JD, Dupont KM, Bajin M, Huebsch N, Mooney DJ, Hutmacher DW, Guldberg RE. Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects. Bone. September 2011;49(4):485-492.
2020	Klosterhoff BS, Kaiser J, Nelson BD, Karipott SS, Ruehle MA, Hollister SJ, Weiss JA, Ong KG, Willett NJ, Guldberg RE. Wireless sensor enables longitudinal monitoring of regenerative niche mechanics during rehabilitation that enhance bone repair. Bone. June 2020;135:115311.
2020	Chen CH, Hsu EL, Stupp SI. Supramolecular self-assembling peptides to deliver bone morphogenetic proteins for skeletal regeneration. Bone. December 2020;141:115565.
2012	Diab T, Pritchard EM, Uhrig BA, Boerckel JD, Kaplan DL, Guldberg RE. A silk hydrogel-based delivery system of bone morphogenetic protein for the treatment of large bone defects. J Mech Behav Biomed Mater. August 2012;11:123-131.
2016	McDermott AM, Mason DE, Lin AS, Guldberg RE, Boerckel JD. Influence of structural load-bearing scaffolds on mechanical load- and BMP-2-mediated bone regeneration. J Mech Behav Biomed Mater. September 2016;62:169-181.
2012	Boerckel JD, Kolambkar YM, Stevens HY, Lin ASP, Dupont KM, Guldberg RE. Effects of in vivo mechanical loading on large bone defect regeneration. J Orthop Res. July 2012;30(7):1067-1075.
2023	Priddy LB, Krishnan L, Hettiaratchi MH, Karthikeyakannan S, Gupte N, Guldberg RE. Amniotic membrane attenuates heterotopic ossification following high-dose bone morphogenetic protein-2 treatment of segmental bone defects. J Orthop Res. January 2023;41(1):130-140.
2011	Boerckel JD, Uhrig BA, Willett NJ, Huebsch N, Guldberg RE. Mechanical regulation of vascular growth and tissue regeneration in vivo. Proc Natl Acad Sci USA. September 13, 2011;108(37):E674-E680.
2013	Willett NJ, Li M-TA, Uhrig BA, Boerckel JD, Huebsch N, Lundgren TL, Warren GL, Guldberg RE. Attenuated human bone morphogenetic protein-2–mediated bone regeneration in a rat model of composite bone and muscle injury. Tissue Eng Part C Methods. April 2013;19(4):316-325.
2011	Boerckel JD. Mechanical Regulation of Bone Regeneration and Vascular Growth in Vivo [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2011.
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2016	Hettiaratchi MH. Heparin Microparticle-Mediated Delivery of BMP-2 and Pluripotent Stem Cell Morphogens for Bone Repair [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; December 2016.
2019	Klosterhoff BS. Mechanobiological Regulation of Early Stage Bone Repair [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2019.
2019	Ruehle MA. Cell-Based Vascular Therapeutics for Bone Regeneration [PhD thesis]. Atlanta, GA: Georgia Institute of Technology; August 2019.
2019	McDermott AM. Mechanical Regulation of Progenitor Cell Differentiation During Endochondral Ossification [PhD thesis]. University of Notre Dame; July 2019.
2018	De Mori A. Silver Nanowires and Their Potential Use as 3D Scaffolds for Biomedical Applications [PhD thesis]. Portsmouth, England: University of Portsmouth; October 2018.
2015	Tseng L-F. Shape Memory Electrospun Scaffolds for Cell Mechanobiology and Bone Regenerative Applications [PhD thesis]. University of Syracuse; December 2015.
2018	Daly A. 3D Bioprinting of Developmentally Inspired Templates for Bone and Joint Regeneration [PhD thesis]. Trinity College Dublin; March 2018.