A facile strategy for tuning the density of surface-grafted biomolecules for melt extrusion-based additive manufacturing applications

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维普
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外文摘要：Melt extrusion-based additive manufacturing(ME-AM)is a promising technique to fabricate porous scaffolds for tissue engi-neering applications.However,most synthetic semicrystalline polymers do not possess the intrinsic biological activity required to control cell fate.Grafting of biomolecules on polymeric surfaces of AM scaffolds enhances the bioactivity of a construct;however,there are limited strategies available to control the surface density.Here,we report a strategy to tune the surface density of bioactive groups by blending a low molecular weight poly(ε-caprolactone)5k(PCL5k)containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL75k at different ratios.Stable porous three-dimensional(3D)scaf-folds were then fabricated using a high weight percentage(75 wt.%)of the low molecular weight PCL5k.As a proof-of-concept test,we prepared films of three different mass ratios of low and high molecular weight polymers with a thermopress and reacted with an alkynated fluorescent model compound on the surface,yielding a density of 201-561 pmol/cm2.Subsequently,a bone morphogenetic protein 2(BMP-2)-derived peptide was grafted onto the films comprising different blend compositions,and the effect of peptide surface density on the osteogenic differentiation of human mesenchymal stromal cells(hMSCs)was assessed.After two weeks of culturing in a basic medium,cells expressed higher levels of BMP receptor II(BMPRII)on films with the conjugated peptide.In addition,we found that alkaline phosphatase activity was only significantly enhanced on films contain-ing the highest peptide density(i.e.,561 pmol/cm2),indicating the importance of the surface density.Taken together,these results emphasize that the density of surface peptides on cell differentiation must be considered at the cell-material interface.Moreover,we have presented a viable strategy for ME-AM community that desires to tune the bulk and surface functionality via blending of(modified)polymers.Furthermore,the use of alkyne-azide"click"chemistry enables spatial control over bioconjugation of many tissue-specific moieties,making this approach a versatile strategy for tissue engineering applications.

外文关键词：

Additive manufacturingBlendingSurface functionalizationSurface densityClick chemistryHuman mesenchymal stromal cell(hMSC)differentiation

作者：

I.A.O.Beeren、G.Dos Santos、P.J.Dijkstra、C.Mota、J.Bauer、H.Ferreira、Rui L.Reis、N.Neves、S.Camarero-Espinosa、M.B.Baker、L.Moroni

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作者单位：

Department of Complex Tissue Regeneration,MERLN Institute for Technology-Inspired Regenerative Medicine,Maastricht University,6229 ER Maastricht,The Netherlands

3B's Research Group,I3Bs-Research Institute on Biomaterials,Biodegradables and Biomimetics,Headquarters of the European Institute of Excellence on Tissue Engineering and Regenerative Medicine,University of Minho,AvePark,Zona Industrial da Gandra,4805-017 Barco,Guimarães,Portugal

ICVS/3B's-PT Government Associate Laboratory,4806-909 Braga/Guimarães,P

ICVS/3B's-PT Government Associate Laboratory,4806-909 Braga/Guimarães,Portugal

POLYMAT,University of the Basque Country UPV/EHU,20018 Donostia/San Sebastián,Spain

IKERBASQUE,Basque Foundation for Science,48009 Bilbao,Spain

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基金：

European Research Council starting grant"Cell Hybridge"under the Horizon framework program(2020)Province of Limburg

项目编号：

637308

出版年：

2024

DOI：

10.1007/s42242-024-00286-2

生物设计与制造(英文)

ISSN：2096-5524

年,卷(期)：2024.7(3)