Biomaterial-Mediated Protein Expression Induced by Peptide-mRNA Nanoparticles Embedded in Lyophilized Collagen Scaffolds.
Biomaterial-Mediated Protein Expression Induced by Peptide-mRNA Nanoparticles Embedded in Lyophilized Collagen Scaffolds.
复制标题
生物材料介导的蛋白质表达诱导肽mRNA纳米颗粒包埋在冻干胶原支架。
DOI：
10.3390/pharmaceutics14081619
复制
发表时间：
2022-08-02
期刊：
影响因子：
5.4
通讯作者：
Brock, Roland
中科院分区：
文献类型：
--
作者：
Oude Egberink, Rik;Zegelaar, Helen M.;El Boujnouni, Najoua;Versteeg, Elly M. M.;Daamen, Willeke F.;Brock, Roland
关键词：
在我们的老龄化社会中，患有愈合不良的骨缺损的患者数量增加。骨形态发生蛋白（BMP）在临床上用于促进骨再生。然而，对BMP递送的不良控制以及因此的活性需要高剂量，从而导致不良作用和增加的成本。已经证明，信使RNA（mRNA）由于局部摄取和限制于作用位点的延长表达而提供了蛋白质递送的上级替代方案。在这里，我们提出了多孔胶原蛋白支架纳入肽-mRNA纳米颗粒（NP）的发展。通过简单地混合阳离子细胞穿透肽PepFect 14（PF 14）和mRNA的水溶液来产生纳米颗粒。肽-mRNA复合物均匀地分布在整个支架中，并且基质完全保留了细胞附着和活力。有一个明确的蛋白质表达的mRNA的掺入量的依赖性。重要的是，冻干后，胶原支架中的mRNA制剂在4 °C下也保持活性两周。总的来说，我们的研究结果表明，胶原蛋白支架纳入肽-mRNA复合物有希望作为现成的功能性生物材料在再生医学中的应用，并构成一个可行的替代脂质为基础的mRNA制剂。
In our aging society, the number of patients suffering from poorly healing bone defects increases. Bone morphogenetic proteins (BMPs) are used in the clinic to promote bone regeneration. However, poor control of BMP delivery and thus activity necessitates high doses, resulting in adverse effects and increased costs. It has been demonstrated that messenger RNA (mRNA) provides a superior alternative to protein delivery due to local uptake and prolonged expression restricted to the site of action. Here, we present the development of porous collagen scaffolds incorporating peptide-mRNA nanoparticles (NPs). Nanoparticles were generated by simply mixing aqueous solutions of the cationic cell-penetrating peptide PepFect14 (PF14) and mRNA. Peptide-mRNA complexes were uniformly distributed throughout the scaffolds, and matrices fully preserved cell attachment and viability. There was a clear dependence of protein expression on the incorporated amount of mRNA. Importantly, after lyophilization, the mRNA formulation in the collagen scaffolds retained activity also at 4 °C over two weeks. Overall, our results demonstrate that collagen scaffolds incorporating peptide-mRNA complexes hold promise as off-the-shelf functional biomaterials for applications in regenerative medicine and constitute a viable alternative to lipid-based mRNA formulations.
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DOI：
10.1016/j.mtbio.2021.100105
发表时间：
2021-03
期刊：
Materials today. Bio
影响因子：
--
作者：
Andrée L;Yang F;Brock R;Leeuwenburgh SCG
通讯作者：
Leeuwenburgh SCG
DOI：
10.1056/nejmoa2035389
发表时间：
2021-02-04
期刊：
The New England journal of medicine
影响因子：
--
作者：
Baden LR;El Sahly HM;Essink B;Kotloff K;Frey S;Novak R;Diemert D;Spector SA;Rouphael N;Creech CB;McGettigan J;Khetan S;Segall N;Solis J;Brosz A;Fierro C;Schwartz H;Neuzil K;Corey L;Gilbert P;Janes H;Follmann D;Marovich M;Mascola J;Polakowski L;Ledgerwood J;Graham BS;Bennett H;Pajon R;Knightly C;Leav B;Deng W;Zhou H;Han S;Ivarsson M;Miller J;Zaks T;COVE Study Group
通讯作者：
COVE Study Group
影响因子：
5
作者：
Damiati LA;El-Messeiry S
通讯作者：
El-Messeiry S
影响因子：
--
作者：
Epstein, Nancy E
通讯作者：
Epstein, Nancy E
达到脂质纳米颗粒的长期稳定性：检查pH，温度和冻干的影响。
影响因子：
8
作者：
Ball RL;Bajaj P;Whitehead KA
通讯作者：
Whitehead KA