Abstract

Effective graft technologies for bone repair have been a primary focus in the field of bone tissue engineering. We have previously fabricated and examined a nanocomposite composed of polyurethane, nano-hydroxyapatite, and decellularized bone particles, which demonstrated osteobiologic characteristics. To evaluate the underlying mechanisms of this biomaterial, human adipose-derived mesenchymal stem cell seeded scaffolds were assessed using a combinatorial approach of transcriptomic and metabolomic analyses. Data from osteogenic and signal transduction polymerase chain reaction arrays and small molecule abundances, measured through liquid chromatography–mass spectrometry, were cross-examined using Integrated Molecular Pathway Level Analysis, Database for Annotation, Visualization, and Integrated Discovery, and ConsensusPathDB online tools to generate a fundamental collection of scaffold-influenced pathways. Results demonstrated upregulation of key osteogenic, cellular adhesion cell signaling markers and indicated that Hedgehog and Wnt signaling pathways were primary candidates for the osteobiologic mechanisms of the scaffold design. The detection of complimentary metabolites, such as ascorbate, further indicates that scaffolds generate intricate cellular environments, promoting cell attachment and subsequent osteodifferentiation.

Highlights

  • The field of bone tissue engineering faces unique challenges in biomaterial design stemming largely from the highly dynamic nature of the target tissue

  • We have previously reported the fabrication of a nanocomposite composed of nano-hydroxyapatite/ polyurethane (PU) film layers with interspersing layers of decellularized bovine bone particles (DBPs), which demonstrated biocompatibility and osteobiologic characteristics, both in vitro and in vivo.[4,9]

  • Transcriptomics Established techniques using cells cultured for 21 days with osteodifferentiation media were used as a positive control to assess cells seeded onto scaffolds and cultured for 5 days

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Summary

Introduction

The field of bone tissue engineering faces unique challenges in biomaterial design stemming largely from the highly dynamic nature of the target tissue. Native bone undergoes continuous remodeling through osteoblastic (OB) and osteoclastic activity to accommodate for mechanical forces exerted on the body and provide structural support. For this reason, noncompromised bone tissue, as opposed to that observed in osteoporotic or geriatric individuals, is innately capable of repairing sizable injuries. For cases of tissue damage that result in defect sizes that exceed the reparative capacities of native bone, or for accelerated repair, the application of a graft material is necessary.[1]. The gold standard for such graft material is the use of autologous tissue, as this eliminates concerns of immunogenic reaction and provides an optimal substrate for cellular on-growth and eventual integration.

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