Microenvironment-optimized gastrodin-functionalized scaffolds orchestrate asymmetric division of recruited stem cells in endogenous bone regeneration.

Publisher: BioMed Central Country of Publication: England NLM ID: 101152208 Publication Model: Electronic Cited Medium: Internet ISSN: 1477-3155 (Electronic) Linking ISSN: 14773155 NLM ISO Abbreviation: J Nanobiotechnology Subsets: MEDLINE

Original Publication: London : BioMed Central, 2003-

Glucosides*/pharmacology ; Glucosides*/chemistry ; Bone Regeneration*/drug effects ; Benzyl Alcohols*/pharmacology ; Benzyl Alcohols*/chemistry ; Tissue Scaffolds*/chemistry ; Mesenchymal Stem Cells*/drug effects ; Mesenchymal Stem Cells*/metabolism ; Mesenchymal Stem Cells*/cytology ; Osteogenesis*/drug effects ; Rats, Sprague-Dawley*; Animals ; Rats ; Cell Differentiation/drug effects ; Asymmetric Cell Division ; Osteoporosis/drug therapy ; Female ; Cell Proliferation/drug effects ; Cellular Microenvironment/drug effects ; Cells, Cultured

The regeneration of osteoporotic bone defects remains challenging as the critical stem cell function is impaired by inflammatory microenvironment. Synthetic materials that intrinsically direct osteo-differentiation versus self-renewal of recruited stem cell represent a promising alternative strategy for endogenous bone formation. Therefore, a microenvironmentally optimized polyurethane (PU) /n-HA scaffold to enable sustained delivery of gastrodin is engineered to study its effect on the osteogenic fate of stem cells. It exhibited interconnected porous networks and an elevated sequential gastrodin release pattern to match immune-osteo cascade concurrent with progressive degradation of materials. In a critical-sized femur defect model of osteoporotic rat, 5% gastrodin-PU/n-HA potently promoted neo-bone regeneration by facilitating M2 macrophage polarization and CD146 ⁺ host stem cell recruitment to defective site. The implantation time-dependently increased the bone marrow mesenchymal stem cell (BMSC) population, and further culture of BMSCs showed a robust ability of proliferation, migration, and mitochondrial resurgence. Of note, some of cell pairs produced one stemness daughter cell while the other committed to osteogenic lineage in an asymmetric cell division (ACD) manner, and a much more compelling ACD response was triggered when 5% gastrodin-PU/n-HA implanted. Further investigation revealed that one-sided concentrated presentation of aPKC and β-catenin in dividing cells effectively induced asymmetric distribution, which polarized aPKC biased the response of the daughter cells to Wnt signal. The asymmetric cell division in skeletal stem cells (SSCs) was mechanically comparable to BMSCs and also governed by distinct aPKC and β-catenin biases. Concomitantly, delayed bone loss adjacent to the implant partly alleviated development of osteoporosis. In conclusion, our findings provide insight into the regulation of macrophage polarization combined with osteogenic commitment of recruited stem cells in an ACD manner, advancing scaffold design strategy for endogenous bone regeneration.
Competing Interests: Declarations Competing interests The authors declare no competing interests.
(© 2024. The Author(s).)

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82160175 National Natural Science Foundation of China; 82260366 National Natural Science Foundation of China; 202201AT070136 Yunnan Science and Technology Program; 202301AY070001-032 Yunnan Science and Tehcnology Program

Keywords: Asymmetric cell division; Endogenous bone regeneration; Gastrodin delivery; Microenvironment regulation; Osteogenic differentiation

5YS9U2W3RQ (gastrodin)
0 (Glucosides)
0 (Benzyl Alcohols)

Date Created: 20241120 Date Completed: 20241120 Latest Revision: 20241122

20250114

PMC11577785

10.1186/s12951-024-02886-7

39563380