Biomolecule Gradient in Micropatterned Nanofibrous Scaffold for Spatiotemporal Release

Abstract

Controlled molecule release from scaffolds can dramatically increase the scaffold ability of directing tissue regeneration in vitro and in vivo. Crucial to the regeneration is precise regulation over release direction and kinetics of multiple molecules (small genes, peptides, or larger proteins). To this end, we developed gradient micropatterns of electrospun nanofibers along the scaffold thickness through programming the deposition of heterogeneous nanofibers of poly(ε-caprolactone) (PCL) and poly(D,L-lactide-co-glycolide) acid (PLGA). Confocal images of the scaffolds containing fluorophore-impregnated nanofibers demonstrated close matching of actual and designed gradient fiber patterns; thermal analyses further showed their matching in the composition. Using acid-terminated PLGA (PLGAac) and ester-terminated PLGA (PLGAes) to impregnate molecules in the PCL-PLGA scaffolds, we demonstrated for the first time their differences in nanofiber degeneration and molecular weight change during degradation. PLGAac nanofibers were more stable with gradual and steady increase in the fiber diameter during degradation, resulting in more spatially confined molecule delivery from PCL-PLGA scaffolds. Thus, patterns of PCL-PLGAac nanofibers were used to design versatile controlled delivery scaffolds. To test the hypothesis that molecule-impregnated PLGAac in the gradient-patterned PCL-PLGAac scaffolds can program various modalities of molecule release, model molecules, including small fluorophores and larger proteins, were respectively used for time-lapse release studies. Gradient-patterns were used as building blocks in the scaffolds to program simultaneous release of one or multiple proteins to one side or, respectively, to the opposite sides of scaffolds for up to 50 days. Results showed that the separation efficiency of molecule delivery from all the scaffolds with a thickness of 200 μm achieved >88% for proteins and >82% for small molecules. In addition to versatile spatially controlled delivery, micropatterns were designed to program sequential release of proteins. The hierarchically structured materials presented here may enable development of novel multifunctional scaffolds with defined 3D dynamic microenvironments for tissue regeneration.

Ordered and Kinetically Discrete Sequential Protein Release from Biodegradable Thin Films

“…[10] Recapitulating a multi-drug dosing regimen with a biodegradable, controlled release formulation remains a challenge, as drug release kinetics frequently have significant overlap, especially during the early phases of release. Some approaches have utilized combinations of different hydrophobic polyesters (for example, poly(lactic-co-glycolic acid) or PLGA, poly(e-caprolactone), and poly(3-hydroxybutyrateco-3-hydroxyvalerate)) in strategic arrangements, [11] as well as their combinations with hydrogels. [12] Others have simply used scaffolds based on modified alginate [13] or gelatin [6h, 14] to manipulate release kinetics.…”

Dual drug spatiotemporal release from functional gradient scaffolds prepared using 3D bioprinting and electrospinning

“…In addition, the mechanical strength of electrospun nanofiber scaffolds is very poor, so it is not possible to build mechanically strong scaffolds as a solution for osteochondral defect repair . For precise regulation, few studies have investigated strategies of spatiotemporal controlled multidrug release .…”

A review on electrospun bio-based polymers for water treatment

“…This can be done by spinning both solutions, fed from different reservoirs, in a programmed way such that both solutions reach the collector at the same time [121]. Another way is the depositing of the nanofibres in a sequential way, where one polymer solution is first deposited followed by the other [122]. In these methods the syringes filled with different polymers are placed opposite each other with the collector between them, and perpendicular to the principal axis of the collector.…”