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An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis.

ABSTRACT: Limited stem cells, poor stretchability and mismatched interface fusion have plagued the reconstruction of cranial defects by cell-free scaffolds. Here, we designed an instantly fixable and self-adaptive scaffold by dopamine-modified hyaluronic acid chelating Ca²⁺ of the microhydroxyapatite surface and bonding type I collagen to highly simulate the natural bony matrix. It presents a good mechanical match and interface integration by appropriate calcium chelation, and responds to external stress by flexible deformation. Meanwhile, the appropriate matrix microenvironment regulates macrophage M2 polarization and recruits endogenous stem cells. This scaffold promotes the proliferation and osteogenic differentiation of BMSCs in vitro, as well as significant ectopic mineralization and angiogenesis. Transcriptome analysis confirmed the upregulation of relevant genes and signalling pathways was associated with M2 macrophage activation, endogenous stem cell recruitment, angiogenesis and osteogenesis. Together, the scaffold realized 97 and 72% bone cover areas after 12 weeks in cranial defect models of rabbit (Φ = 9 mm) and beagle dog (Φ = 15 mm), respectively.

SUBMITTER: Lu G

PROVIDER: S-EPMC9076642 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis.

Lu Gonggong G Xu Yang Y Liu Quanying Q Chen Manyu M Sun Huan H Wang Peilei P Li Xing X Wang Yuxiang Y Li Xiang X Hui Xuhui X Luo En E Liu Jun J Jiang Qing Q Liang Jie J Fan Yujiang Y Sun Yong Y Zhang Xingdong X

Nature communications 20220506 1

Limited stem cells, poor stretchability and mismatched interface fusion have plagued the reconstruction of cranial defects by cell-free scaffolds. Here, we designed an instantly fixable and self-adaptive scaffold by dopamine-modified hyaluronic acid chelating Ca<sup>2+</sup> of the microhydroxyapatite surface and bonding type I collagen to highly simulate the natural bony matrix. It presents a good mechanical match and interface integration by appropriate calcium chelation, and responds to exter ...[more]

PMID: 35523800

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Project description:Therapeutic options are limited for severe lung injury and disease as the spontaneous regeneration of functional alveolar is terminated owing to the weakness of the inherent stem cells and the dyscrasia of the niche. Umbilical cord mesenchymal-derived stem cells (UC-MSCs) have been applied to clinical trials to promote lung repair through stem cell niche restruction. However, the application of UC-MSCs is hampered by the effectiveness of cell transplantation with few cells homing to the injury sites and poor retention, survival, and proliferation in vivo. In this study, we constructed an artificial three-dimensional (3D) biomimetic scaffold-based MSCs implant to establish a beneficial regeneration niche for endogenous stem cells in situ lung regeneration. The therapeutic potential of 3D biomimetic scaffold-based MSCs implants was evaluated by 3D culture in vitro. And RNA sequencing (RNA-Seq) was mapped to explore the gene expression involved in the niche improvement. Next, a model of partial lung resection was established in rats, and the implants were implanted into the operative region. Effects of the implants on rat resected lung injury repair were detected. The results revealed that UC-MSCs loaded on biomimetic scaffolds exerted strong paracrine effects and some UC-MSCs migrated to the lung from scaffolds and had long-term retention to suppress inflammation and fibrosis in residual lungs and promoted vascular endothelial cells and alveolar type II epithelial cells to enter the scaffolds. Then, under the guidance of the ECM-mimicking structures of scaffolds and the stimulation of the remaining UC-MSCs, vascular and alveolar-like structures were formed in the scaffold region. Moreover, the general morphology of the operative lung was also restored. Taken together, the artificial 3D biomimetic scaffold-based MSCs implants induce in situ lung regeneration and recovery after lung destruction, providing a promising direction for tissue engineering and stem cell strategies in lung regeneration.

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Dataset Information

An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis.

Publications

An instantly fixable and self-adaptive scaffold for skull regeneration by autologous stem cell recruitment and angiogenesis.

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