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

Autor: Beeren IAO; Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands., Dos Santos G; 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, Portugal., Dijkstra PJ; Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands., Mota C; Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands., Bauer J; Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands., Ferreira H; 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, Portugal., Reis RL; 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, Portugal., Neves N; 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, Portugal., Camarero-Espinosa S; Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands.; POLYMAT, University of the Basque Country UPV/EHU, 20018 Donostia/San Sebastián, Spain.; IKERBASQUE, Basque Foundation for Science, 48009 Bilbao, Spain., Baker MB; Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands., Moroni L; Department of Complex Tissue Regeneration, MERLN Institute for Technology-Inspired Regenerative Medicine, Maastricht University, 6229 ER Maastricht, The Netherlands.
Jazyk: angličtina
Zdroj: Bio-design and manufacturing [Biodes Manuf] 2024; Vol. 7 (3), pp. 277-291. Date of Electronic Publication: 2024 May 20.
DOI: 10.1007/s42242-024-00286-2
Abstrakt: Melt extrusion-based additive manufacturing (ME-AM) is a promising technique to fabricate porous scaffolds for tissue engineering 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 (PCL 5k ) containing orthogonally reactive azide groups with an unfunctionalized high molecular weight PCL 75k at different ratios. Stable porous three-dimensional (3D) scaffolds were then fabricated using a high weight percentage (75 wt.%) of the low molecular weight PCL 5k . 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/cm 2 . 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 containing the highest peptide density (i.e., 561 pmol/cm 2 ), 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.
Supplementary Information: The online version contains supplementary material available at 10.1007/s42242-024-00286-2.
Competing Interests: Conflict of interestThis paper is to be included in a special issue for which RLR is a guest editor, and he was not involved in the editorial review or the decision to publish this article. The authors declare that they have no conflict of interest.
(© The Author(s) 2024.)
Databáze: MEDLINE
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