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Review
. 2016 Sep;11(6):571-87.
doi: 10.2217/rme-2016-0042. Epub 2016 Aug 23.

The potential impact of bone tissue engineering in the clinic

Ruchi Mishra  1 , Tyler Bishop  1 , Ian L Valerio  1 , John P Fisher  2 , David Dean  1
Affiliations
Review

The potential impact of bone tissue engineering in the clinic

Ruchi Mishra et al. Regen Med. 2016 Sep.

Abstract

Bone tissue engineering (BTE) intends to restore structural support for movement and mineral homeostasis, and assist in hematopoiesis and the protective functions of bone in traumatic, degenerative, cancer, or congenital malformation. While much effort has been put into BTE, very little of this research has been translated to the clinic. In this review, we discuss current regenerative medicine and restorative strategies that utilize tissue engineering approaches to address bone defects within a clinical setting. These approaches involve the primary components of tissue engineering: cells, growth factors and biomaterials discussed briefly in light of their clinical relevance. This review also presents upcoming advanced approaches for BTE applications and suggests a probable workpath for translation from the laboratory to the clinic.

Keywords: 3D printing; additive manufacturing; biomaterials; bioreactor; bone tissue engineering; cell-based therapy.

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Conflict of interest statement

Financial & competing interests disclosure The authors acknowledge partial support from NIH grant R01-DE013740, NIH grant R01-AR061460, the Army, Navy, NIH, Air Force, VA, and Health Affairs to support the AFIRM II effort under award No. W81XWH-14-2-0004. The US Army Medical Research Acquisition Activity is the awarding and administering acquisition office for award No. W81XWH-14-2-0004. Some of the implant design and fabrication technology discussed in this review have been patented and assigned or licensed to Osteoplastics, LLC (Shaker Heights, OH, USA). Other technology discussed in this manuscript is the subject of sponsored research agreements with 3DBioResins (Pepper Pike, OH, USA) and 3DServicePros, LLC (Pepper Pike, OH, USA). D Dean is a co-founder and has an ownership stake in all three companies. D Dean has received compensation from Osteoplastics, LLC. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed. No writing assistance was utilized in the production of this manuscript.

Figures

<b>Figure 1.</b>
Figure 1.. Tissue engineering represented as a stool resting on three legs made of growth factors (and other bioactive molecules), cells and scaffolds.
<b>Figure 2.</b>
Figure 2.. Path for clinical translation of bone tissue-engineered biomaterials, cell-based therapies and growth factors (and other bioactive molecules) that prove effective, first preclinically and then in clinical trials.
<b>Figure 3.</b>
Figure 3.. Various signaling pathways involved in cell signaling.
Many of these pathways such as the Wnt, hedgehog and MAPK signaling pathways are involved in bone formation. The MAPK pathway is activated by growth factors such as EGRF, FGF and PDGF. These growth factors may also be useful in bone tissue engineering (Source: [48]).
<b>Figure 4.</b>
Figure 4.. Diagrammatic representation of osteoblastic differentiation of progenitor bone cells in response to BMP signaling via the Smad pathway.
BMP attaches to extracellular matrix (A) through the binding of integrins (B). The cascade of events after the binding of BMP (C) to its receptors (D) include the activation of R-SMAD (SMAD 1, 5 and 8) through phosphorylation (E), thereafter, binding with SMAD 4 to form a complex that enters the nucleus and binds to DNA causing the transcription of osteoblastic genes.
<b>Figure 5.</b>
Figure 5.. A hypothetical model for a work path that could be used in the future to prepare a patient-specific synthetic bone graft.
CAD: Computer-aided design.
See this image and copyright information in PMC

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