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Enhanced Scaffolds and Stem Cells Combine to Promote Bone Repair

Review of Injectable BMP-2 gene-activated scaffold for the repair of cranial bone defect in micefrom STEM CELLS Translational Medicine by Stuart P. Atkinson

A range of studies has provided ample evidence that stem cells, scaffolds, and growth factors can combine to promote bone repair. Recent research in the laboratories of Bing Wang and Rocky S. Tuan (University of Pittsburgh, PA, USA) has included the development of a visible light‐based projection stereolithographic fabrication method for a biodegradable osteoinductive methacrylated gelatin scaffold [1]. This advanced scaffold displayed compatibility with human bone marrow mesenchymal stem cells (MSCs) and recombinant adeno‐associated viral (rAAV) vectors encoding a full-length cDNA of human bone morphogenetic protein‐2 (BMP‐2) [2]. In this strategy, the slow release of rAAV‐BMP‐2 from the scaffold prompts the ongoing transduction of MSCs after administration to promote long-term osteogenic activity as an exciting novel approach to bone tissue engineering.

In their new STEM CELLS Translational Medicine article, Sun et al. now report on a similar strategy employing a biodegradable, biocompatible, and osteoconductive gelatin scaffold [3, 4] generated via visible light photocrosslinking as an improved one-step injectable approach to the repair of cranial bone defects in a mouse model [5]. In brief, the authors added the rAAV‐BMP‐2 vector and human MSCs to the gelatin during visible light-mediated scaffold formation and then confirmed the robust release of rAAV‐BMP‐2 from the scaffold, the efficient transduction of scaffold-resident MSCs, and their osteogenic induction in the absence of exogenous BMP‐2 supplementation.

Encouragingly, the injection of the MSC/rAAV‐BMP‐2-laden gelatin-based scaffold into surgically created full‐thickness cranial defects in immunodeficient mice [6-8] permitted for effective bone repair by six-weeks post-treatment, as evidenced by increased new bone volume and bone mineral density measured by micro‐computed tomography and the formation of matured trabecular bone tissue measured by H&E staining and immunohistochemical detection of the osteoinductive protein osteocalcin.  Furthermore, the authors reported no signs of cytotoxicity in rAAV‐BMP‐2 transduced MSCs.

Overall, these findings provide evidence for the therapeutic relevance of this straightforward one-step approach to bone tissue engineering, which fosters the safe and ongoing osteogenesis of MSCs seeded within a supportive scaffold. Future research aims include the evaluation of this strategy in larger animal models to assess the potential clinical application in human bone repair and the implementation of autologous MSCs.

For more on how enhanced scaffolds and transduced MSCs can combine to promote bone repair, stay tuned to the Stem Cells Portal!

References

  1. Lin H, Tang Y, Lozito TP, et al., Projection Stereolithographic Fabrication of BMP-2 Gene-activated Matrix for Bone Tissue Engineering. Scientific Reports 2017;7:11327.
  2. Xue J, Lin H, Bean A, et al., One-Step Fabrication of Bone Morphogenetic Protein-2 Gene-Activated Porous Poly-L-Lactide Scaffold for Bone Induction. Molecular Therapy - Methods & Clinical Development 2017;7:50-59.
  3. Paul A, Manoharan V, Krafft D, et al., Nanoengineered biomimetic hydrogels for guiding human stem cell osteogenesis in three dimensional microenvironments. Journal of Materials Chemistry B 2016;4:3544-3554.
  4. Gibbs DMR, Black CRM, Dawson JI, et al., A review of hydrogel use in fracture healing and bone regeneration. Journal of Tissue Engineering and Regenerative Medicine 2016;10:187-198.
  5. Sun K, Lin H, Tang Y, et al., Injectable BMP-2 gene-activated scaffold for the repair of cranial bone defect in mice. STEM CELLS Translational Medicine 2020;9:1631-1642.
  6. Gao X, Lu A, Tang Y, et al., Influences of donor and host age on human muscle-derived stem cell-mediated bone regeneration. Stem Cell Research & Therapy 2018;9:316.
  7. Gao X, Usas A, Tang Y, et al., A comparison of bone regeneration with human mesenchymal stem cells and muscle-derived stem cells and the critical role of BMP. Biomaterials 2014;35:6859-6870.
  8. Gao X, Usas A, Lu A, et al., BMP2 is Superior to BMP4 for Promoting Human Muscle-Derived Stem Cell-Mediated Bone Regeneration in a Critical-Sized Calvarial Defect Model. Cell Transplantation 2013;22:2393-2408.