Laboratory of Advanced Biomaterials, Research School of Electrical, Energy and Materials Engineering, Australian National University, Canberra, ACT, 2601, Australia.
The Graeme Clark Institute, The University of Melbourne, Parkville, VIC, 3010, Australia.
Nat Commun. 2023 Jan 28;14(1):457. doi: 10.1038/s41467-023-36133-8.
Injectable biomimetic hydrogels have great potential for use in regenerative medicine as cellular delivery vectors. However, they can suffer from issues relating to hypoxia, including poor cell survival, differentiation, and functional integration owing to the lack of an established vascular network. Here we engineer a hybrid myoglobin:peptide hydrogel that can concomitantly deliver stem cells and oxygen to the brain to support engraftment until vascularisation can occur naturally. We show that this hybrid hydrogel can modulate cell fate specification within progenitor cell grafts, resulting in a significant increase in neuronal differentiation. We find that the addition of myoglobin to the hydrogel results in more extensive innervation within the host tissue from the grafted cells, which is essential for neuronal replacement strategies to ensure functional synaptic connectivity. This approach could result in greater functional integration of stem cell-derived grafts for the treatment of neural injuries and diseases affecting the central and peripheral nervous systems.
可注射仿生水凝胶作为细胞递药载体，在再生医学中有很大的应用潜力。然而，由于缺乏成熟的血管网络，它们可能会出现缺氧相关问题，包括细胞存活率、分化和功能整合差。在这里，我们构建了一种肌红蛋白：肽混合水凝胶，它可以同时将干细胞和氧气输送到大脑，以支持植入，直到血管自然形成。我们表明，这种混合水凝胶可以调节祖细胞移植物内的细胞命运特化，导致神经元分化显著增加。我们发现，水凝胶中添加肌红蛋白会导致移植物中的细胞在宿主组织内产生更广泛的神经支配，这对于神经元替代策略至关重要，以确保功能性突触连接。这种方法可能会使干细胞衍生移植物的功能整合程度更高，从而治疗中枢和周围神经系统损伤和疾病。
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