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Optimized Scaffold-Stem Cell Combination for Enhanced Bone Repair

Review of “Tissue‐specific mesenchymal stem cell‐dependent osteogenesis in highly porous chitosan‐based bone analogs” from STEM CELLS Translational Medicine by Stuart P. Atkinson

As reported in a recent STEM CELLS Translational Medicine article [1], researchers from the laboratories of Sujata Mohanty (All India Institute of Medical Sciences, New Delhi, India) and Shibashish Giri (University of Leipzig, Leipzig, Germany) explored the potential of a three-dimensional porous multimaterial composite scaffold in combination with various mesenchymal stem cell (MSC) types in the hope of encountering an optimal pairing for enhanced bone repair/regeneration.

The multimaterial scaffold comprised a mixture of polycaprolactone (PCL), a biocompatible polymer with a slow degradation rate blended with chitosan (CHT) to enhance wettability, accelerate PCL degradation, and improve cytocompatibility [2] and hydroxyapatite (HA) to promote early bone integration [3]. The authors also compared the growth of three types of human MSCs (bone marrow, adipose, and Wharton’s jelly MSCs) in this multimaterial scaffold to compare the extent of osteogenic differentiation in vitro as a function of their origin [4, 5].

Midha et al. discovered that Wharton’s jelly MSCs displayed the most significant degree of attachment to the multimaterial scaffold (a 3:3:2 ratio of CHT/HA/PCL) and exhibited enhanced metabolic activity; however, analysis via scanning electron microscopy and gene and protein expression profiling instead provided evidence that the bone marrow MSCs displayed the most significant levels of osteogenesis. Changes to gene expression levels included an increase in alkaline phosphatase, collagen type I, osteocalcin, and bone morphogenetic protein 4 expression, while alterations to marker proteins included increases in collagen type I, β‐catenin, osteocalcin, and sclerostin expression.

In agreement with their in vitro findings, the authors also established that bone marrow MSCs cultured on the multimaterial scaffold provided for early osseointegration and significant levels of bone formation, as evidenced by microcomputed tomography (micro‐CT) analysis and histology, after transplantation into a rat orthotopic load‐bearing tibial defect model.

The authors now hope to advance the evaluation of bone marrow MSCs cultured within their novel multimaterial scaffold to larger animals in the hope of validating their potential in repairing critical‐sized defects.

For more on the application of composite scaffold materials and MSCs in enhanced bone repair/regeneration strategies, stay tuned to the Stem Cells Portal!


References

  1. Midha S, Jain KG, Bhaskar N, et al., Tissue-specific mesenchymal stem cell-dependent osteogenesis in highly porous chitosan-based bone analogs. STEM CELLS Translational Medicine 2021;10:303-319.
  2. Mad Jin R, Sultana N, Baba S, et al., Porous PCL/Chitosan and nHA/PCL/Chitosan Scaffolds for Tissue Engineering Applications: Fabrication and Evaluation. Journal of Nanomaterials 2015;2015:357372.
  3. Meirelles L, Arvidsson A, Andersson M, et al., Nano hydroxyapatite structures influence early bone formation. Journal of Biomedical Materials Research Part A 2008;87A:299-307.
  4. Xie X, Wang Y, Zhao C, et al., Comparative evaluation of MSCs from bone marrow and adipose tissue seeded in PRP-derived scaffold for cartilage regeneration. Biomaterials 2012;33:7008-7018.
  5. Kern S, Eichler H, Stoeve J, et al., Comparative Analysis of Mesenchymal Stem Cells from Bone Marrow, Umbilical Cord Blood, or Adipose Tissue. STEM CELLS 2006;24:1294-1301.