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首页> 外文期刊>Materials science & engineering >Improved vascularisation but inefficient in vivo bone regeneration of adipose stem cells and poly-3-hydroxybutyrate-co-3-hydroxyvalerate scaffolds in
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Improved vascularisation but inefficient in vivo bone regeneration of adipose stem cells and poly-3-hydroxybutyrate-co-3-hydroxyvalerate scaffolds in

机译:改善脂肪干细胞和聚-3-羟基丁酸酯-co-3-羟基戊酸酯支架的体内骨再生效率低下

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摘要

Bone defects are a common clinical situation. However, bone regeneration remains a challenge and faces the limitation of poor engraftment due to deficient vascularisation. Poly-3-hydroxybutyrate-co-3-hydroxyvalerate (PHB-HV) and human adipose stem cells (hASC) are promising for vascularisation and bone regeneration. Therefore, we sought to investigate the bone regenerative capacity of hASCs cultured in allogeneic human serum (aHS) and PHB-HV scaffolds in a nude mouse model of the critical-sized calvarial defect We evaluated bone healing for three treatment groups: empty (control), PHB-HV and PHB-HV + hASCs. The pre-implant analysis showed that hASCs colonised the PHB-HV scaffolds maintaining cell viability before implantation. Histological analysis revealed that PHB-HV scaffolds were tolerated in vivo; they integrated with adjacent tissue eliciting a response like a foreign body reaction, and tiny primary bone was observed only in the PHB-HV group. Also, the mu-CT analysis revealed only approximately 10% of new bone in the bone defect area in both the PHB-HV and PHB-HV + hASCs groups. The expression of BGLAP and its protein (osteocalcin) by PHB-HV + hASCs group and native bone was similar while the other bone markers RUNX2, ALPL and COL1A1 were upregulated, but this expression remained significantly lower compared to the native bone. Nevertheless, the PHB-HV group showed neovascularisation at 12 weeks post-implantation while PHB-HV + hASCs group also exhibited higher VEGFA expression as well as a higher number of vessels at 4 weeks post-implantation, and, consequently, earlier neovascularisation. This neovascularisation must be due to scaffold architecture, improved by hASCs, that survived for the long term in vivo in the PHB-HV + hASCs group. These results demonstrated that hASCs cultured in aHS combined with PHB-HV scaffolds were ineffective to promote bone regeneration, although the construct of hASCs + PHB-HV in xeno-free conditions improved scaffold vascularisation representing a strategy potentially promising for other tissue engineering applications.
机译:骨缺损是一种常见的临床情况。然而,由于血管化不足,骨再生仍然是挑战并且面临着植入不良的局限性。聚-3-羟基丁酸酯-co-3-羟基戊酸酯(PHB-HV)和人类脂肪干细胞(hASC)有望用于血管形成和骨骼再生。因此,我们试图研究在同种异体人类血清(aHS)和PHB-HV支架中培养的hASCs在关键大小颅盖缺损的裸鼠模型中的骨再生能力。我们评估了三个治疗组的骨愈合:空(对照组) ,PHB-HV和PHB-HV + hASC。植入前的分析表明,hASCs在PHB-HV支架上定植,在植入前维持细胞活力。组织学分析表明,PHB-HV支架在体内是可耐受的。它们与邻近组织融合,引起类似异物反应的反应,仅在PHB-HV组中观察到微小的初级骨骼。而且,mu-CT分析显示,在PHB-HV和PHB-HV + hASCs组中,骨缺损区域中只有大约10%的新骨。 PHB-HV + hASCs组和天然骨的BGLAP及其蛋白(骨钙素)的表达相似,而其他骨标记RUNX2,ALPL和COL1A1上调,但是与天然骨相比,该表达仍然明显较低。然而,PHB-HV组在植入后12周出现新血管形成,而PHB-HV + hASCs组在植入后4周也表现出较高的VEGFA表达和更多血管,因此,较早出现了新血管形成。这种新血管形成必须归因于hASCs改善的支架结构,该结构在PHB-HV + hASCs组中可在体内长期存活。这些结果表明,尽管在无异种条件下的hASCs + PHB-HV的构建改善了支架的血管形成,这代表了在aHS中与PHB-HV支架相结合的hASCs不能有效地促进骨再生,但该策略代表了其他组织工程应用潜在的战略。

著录项

  • 来源
    《Materials science & engineering》 |2020年第2期|110301.1-110301.11|共11页
  • 作者单位

    Univ Fed Minas Gerais Inst Biol Sci Dept Biochem & Immunol Av Presidente Antonio Carlos 6627 BR-31270901 Belo Horizonte MG Brazil|Univ Fed Juiz de Fora Sch Pharm Dept Pharmaceut Sci R Jose Lourenco Kelmer S-N BR-36036900 Juiz De Fora MG Brazil;

    Univ Fed Minas Gerais Coll Vet Med Dept Clin & Surg Av Presidente Antonio Carlos 6627 BR-31270901 Belo Horizonte MG Brazil;

    Univ Fed Minas Gerais Inst Biol Sci Dept Morphol Av Presidente Antonio Carlos 6627 BR-31270901 Belo Horizonte MG Brazil;

    Alto Univ Fed Univ Espirito Santo Dept Vet Med BR-29500000 Alegre ES Brazil;

    Univ Fed Minas Gerais Inst Biol Sci Dept Biochem & Immunol Av Presidente Antonio Carlos 6627 BR-31270901 Belo Horizonte MG Brazil;

    Univ Fed Minas Gerais Inst Biol Sci Dept Biochem & Immunol Av Presidente Antonio Carlos 6627 BR-31270901 Belo Horizonte MG Brazil|Univ Sao Paulo Dept Immunol Transplants Immunobiol Lab Sao Paulo SP Brazil;

    Univ Minho Headquarters European Inst Excellence Tissue Engn I3Bs Res Inst Biomat Biodegradables & Biomimet 3Bs Res Grp AvePk Parque Ciencia & Tecnol P-4805017 Barco Guimaraes Portugal|PT Govt Associate Lab ICVS 3Bs Associate Lab Campus Gualtar P-4710057 Braga Portugal|Headquarters Univ Minho Discoveries Ctr Regenerat & Precis Med Avepk P-4805017 Barco Guimaraes Portugal;

    Univ Fed Minas Gerais Inst Biol Sci Dept Biochem & Immunol Av Presidente Antonio Carlos 6627 BR-31270901 Belo Horizonte MG Brazil|Univ Fed Minas Gerais Inst Biol Sci Dept Pathol Av Presidente Antonio Carlos 6627 BR-31270901 Belo Horizonte MG Brazil;

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  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

    Tissue engineering; Adipose stem cells; PHB-HV; Neovascularisation; Bone;

    机译:组织工程;脂肪干细胞;PHB-HV;新血管形成;骨;

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