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Review
. 2024 May 27;15(6):145.
doi: 10.3390/jfb15060145.

Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation

Jolene Quek  1 , Catarina Vizetto-Duarte  1 , Swee Hin Teoh  2 , Yen Choo  1
Affiliations
Review

Towards Stem Cell Therapy for Critical-Sized Segmental Bone Defects: Current Trends and Challenges on the Path to Clinical Translation

Jolene Quek et al. J Funct Biomater. .

Abstract

The management and reconstruction of critical-sized segmental bone defects remain a major clinical challenge for orthopaedic clinicians and surgeons. In particular, regenerative medicine approaches that involve incorporating stem cells within tissue engineering scaffolds have great promise for fracture management. This narrative review focuses on the primary components of bone tissue engineering-stem cells, scaffolds, the microenvironment, and vascularisation-addressing current advances and translational and regulatory challenges in the current landscape of stem cell therapy for critical-sized bone defects. To comprehensively explore this research area and offer insights for future treatment options in orthopaedic surgery, we have examined the latest developments and advancements in bone tissue engineering, focusing on those of clinical relevance in recent years. Finally, we present a forward-looking perspective on using stem cells in bone tissue engineering for critical-sized segmental bone defects.

Keywords: bone tissue engineering; clinical translation; critical-sized bone defects; mesenchymal stem cells; microenvironment; regulatory framework; vascularisation.

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Conflict of interest statement

Y.C. is the founder and shareholder of Plasticell Ltd., United Kingdom. S.H.T. is a co-founder of Osteopore International Pte Ltd., Singapore.

Figures

Figure 5
Figure 5
Schematic illustration of (a) an in vivo bioreactor strategy, (b) AV loop-based vascularisation and (c) regenerative matching axial vascularization. Figures are reprinted from (a) Reference [252], (b) Reference [258], and (c) Reference [174], with permission from the authors.
Figure 1
Figure 1
(a) Number of studies published in the last 10 years and (b) their geographical distribution.
Figure 2
Figure 2
Low-serum/serum-free media supported BM-MSC growth and viability. Comparison of the yield (a,c) and viability (b,d) of BM-MSCs expanded in six different commercially available low-serum/serum-free media at P4 (a,b) and P5 (c,d) (* p < 0.05), Figures are reprinted from Reference [57], with permission from the authors.
Figure 3
Figure 3
Rabbit BM-MSCs and bone morphogenetic protein-2 (BMP-2) encapsulated in a chitosan hydrogel in a 3D-printed poly(ε-caprolactone) (PCL) scaffold. (a) (i) Appearance of a 3D PCL scaffold. (ii) SEM images of a PCL scaffold (left) and hybrid scaffold (right). Red rectangle shows the pores of PCL scaffold filled with chitosan gel. Scale bars = 100 μm. (b) (i) A hybrid scaffold of rBM-MSCs encapsulated in a chitosan hydrogel offers similar compressive strength to a PCL scaffold. (ii) CCK-8 assay (left) showed that rBM-MSCs remained viable in a hybrid scaffold with the highest ALP activity (right) (*,# p < 0.05, ** p < 0.01). Figures are reprinted from Reference [75], with permission from the authors.
Figure 4
Figure 4
Schematic diagram of the development process of a customised design of a 3D-printed polycaprolactone-tricalcium phosphate (PCL-TCP) scaffold for the patient’s defect. Cross-sectional images of a CT scan (A). Based on the CT scan, the surface geometry of a 3D model (B) and patient-specific scaffold (C) are 3D-printed. The figure is reprinted from Reference [185], with permission from the authors.
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