Delayed union or nonunion remains an extremely challenging predicament even after the application of currently available engineering scaffolds for the treatment of critical-sized bone defects. The angiogenesis throughout the artificial bone repair scaffold to achieve “angiogenic-osteogenic coupling” is regarded as an effective approach to solving this issue. The newly formed blood vessels can accelerate the supply of oxygen and nutrients, thereby triggering subsequent bone regeneration. Therefore, scaffolds featuring an angiogenic microenvironment that promotes cell adhesion and migration should be designed for superior bone repair. Herein, a magnesium ion-doped hierarchical scaffold is fabricated using a polymer blend system of chitosan/polyethyleneimine with inherent micro-phase separation and complexation. Due to the microscopic sea-island structure and the stable doped magnesium ions, the cell adhesion behavior underwent a significant transformation. Meanwhile, the pathways related to cell adhesion, migration, and angiogenesis are activated, and the critical target thrombospondin 1 is upregulated. Consequently, the cell adhesion capacity is augmented, 6 times the cell migration rate is attained, and the angiogenesis of human umbilical vein endothelial cells is significantly expedited. Eventually, rapid bone ingrowth and satisfactory bone defect repair are approximated in vivo, making the composite scaffold a promising clinical candidate for bone engineering.
Fanyi Huang,Lingyu Sun,Cheng Zhao,Zeping Qiu,Yuanjin Zhao,Wei Jin
As a severe cardiovascular disease, acute myocardial infarction (AMI) has been attaching increasing attention and research for its high morbidity and mortality. In this paper, the novel protein microcapsules integrated hierarchical scaffold is designed for treating AMI model by using microfluidic templates. Based on advanced microfluidic electrospray technique, core-shell microspheres with controllable size are fabricated to build a double barrier for improving the stability of encapsulated drug. These microspheres are further combined with an electrospun polymer membrane to construct the desired hierarchical structure. Based on these designs, the microcapsules can realize long-term drug release while the polymer membrane scaffold exhibits anti-adhesive effect in vitro . By decreasing the level of Angiotensin Ⅱ and inhibiting the Renin-Angiotensin System (RAS) pathway, ACE2 can increase the concentration of Ang (1–7) and enhance its protective function. To evaluate the therapeutic effect, ACE2-encapsulted hierarchical scaffold is applied to AMI mice model, which achieves regional sustainable release and improves the severity of ischemic lesion, with an additional utility of preventing post-operative adhesion. Compared with injecting intramyocardially, implanting hierarchical scaffold avoids excess injury and shows more obvious therapeutic efficacy. These properties suggest that our hierarchical cardiac scaffolds provide a potential drug administration approach for local treatment of AMI.
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