Crosslinker-free collagen gelation for corneal regeneration.

Crosslinker-free collagen gelation for corneal regeneration.
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用于角膜再生的无交联剂胶原凝胶。

DOI:
10.1038/s41598-022-13146-9
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发表时间:
2022-06-01
期刊:
影响因子:
4.6
通讯作者:
Chodosh, James
Chodosh, James
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Islam, Mohammad Mirazul;Chivu, Alexandru;AbuSamra, Dina B.;Saha, Amrita;Chowdhuri, Sumit;Pramanik, Bapan;Dohlman, Claes H.;Das, Debapratim;Argueso, Pablo;Rajaiya, Jaya;Patra, Hirak K.;Chodosh, James

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人工角膜的研发有可能满足角膜移植对供体角膜的需求,因为供体数量远远少于治疗角膜盲所需的数量。基于胶原蛋白的人工角膜作为一种再生选择脱颖而出,具有良好的临床效果。胶原蛋白与化学交联剂交联,化学交联剂会改变胶原蛋白的母体官能团。然而,交联剂通常具有细胞毒性,因此在应用于人体之前,需要将交联剂从植入物中完全去除。此外,交联产品机械强度较弱,容易被酶降解。我们开发了一种无交联剂的超分子凝胶化策略,使用由赖氨酸和半胱氨酸组成的芘共轭二肽两亲物(PyKC);在该策略中,胶原蛋白分子在PyKC网络内相互交织,而胶原蛋白的任何官能团都未被改变。新开发的胶原蛋白植入物(Coll - PyKC)具有光学透明性,能有效阻挡紫外线,具有机械和酶稳定性,并且可以缝合。Coll - PyKC植入物支持所有角膜细胞的生长和功能,在抑制人单核细胞促炎分化的同时触发抗炎分化。Coll - PyKC植入物可以限制人腺病毒的传播。因此,这种无交联剂的策略可用于角膜以及身体其他受损器官的修复、愈合和再生。
Development of an artificial cornea can potentially fulfil the demand of donor corneas for transplantation as the number of donors is far less than needed to treat corneal blindness. Collagen-based artificial corneas stand out as a regenerative option, having promising clinical outcomes. Collagen crosslinked with chemical crosslinkers which modify the parent functional groups of collagen. However, crosslinkers are usually cytotoxic, so crosslinkers need to be removed from implants completely before application in humans. In addition, crosslinked products are mechanically weak and susceptible to enzymatic degradation. We developed a crosslinker free supramolecular gelation strategy using pyrene conjugated dipeptide amphiphile (PyKC) consisting of lysine and cysteine; in which collagen molecules are intertwined inside the PyKC network without any functional group modification of the collagen. The newly developed collagen implants (Coll-PyKC) are optically transparent and can effectively block UV light, are mechanically and enzymatically stable, and can be sutured. The Coll-PyKC implants support the growth and function of all corneal cells, trigger anti-inflammatory differentiation while suppressing the pro-inflammatory differentiation of human monocytes. Coll-PyKC implants can restrict human adenovirus propagation. Therefore, this crosslinker-free strategy can be used for the repair, healing, and regeneration of the cornea, and potentially other damaged organs of the body.
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