Reconstruction of Craniomaxillofacial Bone Defects Using Tissue-Engineering Strategies with Injectable and Non-Injectable Scaffolds

Abstract

Engineering craniofacial bone tissues is challenging due to their complex structures. Current standard autografts and allografts have many drawbacks for craniofacial bone tissue reconstruction; including donor site morbidity and the ability to reinstate the aesthetic characteristics of the host tissue. To overcome these problems; tissue engineering and regenerative medicine strategies have been developed as a potential way to reconstruct damaged bone tissue. Different types of new biomaterials; including natural polymers; synthetic polymers and bioceramics; have emerged to treat these damaged craniofacial bone tissues in the form of injectable and non-injectable scaffolds; which are examined in this review. Injectable scaffolds can be considered a better approach to craniofacial tissue engineering as they can be inserted with minimally invasive surgery; thus protecting the aesthetic characteristics. In this review; we also focus on recent research innovations with different types of stem-cell sources harvested from oral tissue and growth factors used to develop craniofacial bone tissue-engineering strategies.

Keywords: biomaterials; bone; craniofacial reconstruction; growth factors; injectable; scaffolds; stem cells.

Figure 1

Reverse transcription polymerase chain reaction (RT-PCR) results for the osteogenic differentiation of human umbilical cord-derived mesenchymal stem cells (hUCMSCs) and human bone marrow-derived mesenchymal stem cells (hBMMSCs) on macroporous calcium phosphate cements (CPC): (A) alkaline phosphatase (ALP); (B) osteocalcin (OCN); (C) collagen type 1 (Coll I); and (D) runt-related transcription factor 2 (Runx2) gene expressions. The experiments are performed at 1st, 4th, 7th and 14th day. Bars with dissimilar letters indicate significantly different values (p < 0.05). This figure is reproduced with the permission from Weir et al. [47]. Copyright Elsevier, 2013.

Figure 2

High-magnification hematoxylin and eosin (HE) staining images. (A) New bone grew in the interior of the CPC scaffold and was maturing, as indicated by the presence of osteocytes and blood vessels. (B) Both calcified new bone and uncalcified new bone matrix were observed. This figure is reproduced with the permission from Weir et al. [44]. Copyright Acta Materialia, 2014.

Figure 3

(A) Ultimate tensile strength and (B) Young’s moduli of non-crosslinked (black bars) 0.1% genipin and crosslinked (white bars) 7% chitosan nanofibers at different concentrations of hydroxyapatite. (* and ** represent statistical significance at p < 0.05 and p < 0.01). The figure is reproduced with the permission from Lelkes et al. [104]. Copyright Elsevier, 2012.

Figure 4

hBMMSCs encapsulated in RGD-alginate microspheres loaded with anti-BMP2 mAb contribute to bone regeneration in a critical-size calvarial defect model. (a) Micro-computed tomography (micro-CT) results of bone repair in mouse calvarial defects. Regenerated bone is pseudo-colored red; (b) semi-quantitative analysis of bone formation based on micro-CT images; (c) microanatomic representation of repair of critical-size defects in the mouse calvaria after 8 weeks of transplantation at high (40×) and low (4×) magnifications stained with HE. Arrows point to osteocytes in lacunae (Alg: unresorbed alginate, CT: connective tissue); (d) histomorphometric analysis of calvarial defects showing the relative amount of bone formation in the critical size calvarial defect model. (* and ** represent p < 0.05 and p < 0.01 respectively). The figure is reproduced with the permission from Zadeh et al. [64]. Copyright Elsevier, 2013.