Aligned Polyhydroxyalkanoate Blend Electrospun Fibers as Intraluminal Guidance Scaffolds for Peripheral Nerve Repair

Taylor, Caroline S.; Behbehani, Mehri; Glen, Adam; Basnett, Pooja; Gregory, David A.; Lukasiewicz, Barbara; Nigmatullin, Rinat; Claeyssens, Frederik; Roy, Ipsita; Haycock, John W.

doi:10.1021/acsbiomaterials.2c00964

Cited by 13 publications

(27 citation statements)

References 47 publications

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“…It would be hypothesized that based on its physicochemical properties, NGF would be capable of coassembling with SF in a manner similar to LYS or BLAC and exhibit similar bolus release profiles. The DRG explant model was chosen, as it is routinely used to investigate neurite outgrowth, ,− which is highly indicative of nerve regeneration.…”

Section: Resultsmentioning

confidence: 99%

One-Pot Assembly of Drug-Eluting Silk Coatings with Applications for Nerve Regeneration

Fink,

Funnell,

Gilbert

et al. 2023

ACS Biomater. Sci. Eng.

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Clinical use of polymeric scaffolds for tissue engineering often suffers from their inability to promote strong cellular interactions. Functionalization with biomolecules may improve outcomes; however, current functionalization approaches using covalent chemistry or physical adsorption can lead to loss of biomolecule bioactivity. Here, we demonstrate a novel bottom-up approach for enhancing the bioactivity of poly(L-lactic acid) electrospun scaffolds though interfacial coassembly of protein payloads with silk fibroin into nanothin coatings. In our approach, protein payloads are first added into an aqueous solution with Bombyx mori-derived silk fibroin. Phosphate anions are then added to trigger coassembly of the payload and silk fibroin, as well as noncovalent formation of a payload-silk fibroin coating at poly(Llactic) acid fiber surfaces. Importantly, the coassembly process results in homogeneous distribution of protein payloads, with the loading quantity depending on payload concentration in solution and coating time. This coassembly process yields greater loading capacity than physical adsorption methods, and the payloads can be released over time in physiologically relevant conditions. We also demonstrate that the coating coassembly process can incorporate nerve growth factor and that coassembled coatings lead to significantly more neurite extension than loading via adsorption in a rat dorsal root ganglia explant culture model.

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Section: Resultsmentioning

confidence: 99%

One-Pot Assembly of Drug-Eluting Silk Coatings with Applications for Nerve Regeneration

Fink,

Funnell,

Gilbert

et al. 2023

ACS Biomater. Sci. Eng.

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“…[14] We demonstrated a cost-effective, optimized, and scalable method to functionalize glass substrates with NH 2 -presenting groups for peripheral nerve repair, providing substrates with a change in surface wettability, rougher topography, and a lower Young's modulus. [15] This study is the first of its kind to modify PCL fiber scaffolds with 11-aminoundecyl-triethoxysilane for nerve tissue regeneration applications. PCL fiber scaffolds, 10 μm in diameter, were manufactured via electrospinning, confirming fiber diameter and alignment via scanning electron microscopy.…”

Section: Introductionmentioning

confidence: 99%

“…This study is also the first of its kind to investigate silane-modified substrates using a novel 3D ex vivo fiber testing model using dorsal root ganglion (DRG) explants. [6,7,15] We describe a cost-effective and scalable way to functionalize PCL fibers with NH 2 -presenting groups for nerve repair applications.…”

Section: Introductionmentioning

confidence: 99%

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Aminosilane Functionalized Aligned Fiber PCL Scaffolds for Peripheral Nerve Repair

Taylor

Barnes

Koduri

et al. 2023

Macromolecular Bioscience

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Silane modification is a simple and cost‐effective tool to modify existing biomaterials for tissue engineering applications. Aminosilane layer deposition has previously been shown to control NG108‐15 neuronal cell and primary Schwann cell adhesion and differentiation by controlling deposition of ─NH2 groups at the submicron scale across the entirety of a surface by varying silane chain length. This is the first study toreport depositing 11‐aminoundecyltriethoxysilane (CL11) onto aligned Polycaprolactone (PCL) scaffolds for peripheral nerve regeneration. Fibers are manufactured via electrospinning and characterized using water contact angle measurements, atomic force microscopy (AFM), and X‐ray photoelectron spectroscopy (XPS). Confirmed modified fibers are investigated using in vitro cell culture of NG108‐15 neuronal cells and primary Schwann cells to determine cell viability, cell differentiation, and phenotype. CL11‐modified fibers significantly support NG108‐15 neuronal cell and Schwann cell viability. NG108‐15 neuronal cell differentiation maintains Schwann cell phenotype compared to unmodified PCL fiber scaffolds. 3D ex vivo culture of Dorsal root ganglion explants (DRGs) confirms further Schwann cell migration and longer neurite outgrowth from DRG explants cultured on CL11 fiber scaffolds compared to unmodified scaffolds. Thus, a reproducible and cost‐effective tool is reported to modify biomaterials with functional amine groups that can significantly improve nerve guidance devices and enhance nerve regeneration.

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“…Recently, not only scl-PHAs, but also mcl-PHAs have been investigated for their application in nerve regeneration, due to exhibiting mechanical properties closer to that of native nerve tissue, compared to P(3HB) and FDA-approved polymers PLLA, poly ε-caprolactone (PCL) and PLGA [ 3 , 4 , 14 ]. Homopolymers of poly(3‐hydroxyoctanoate), P(3HO), P(3HB) and their blends were developed and evaluated for their nerve regeneration [ 23 , 24 ]. It was found that both neat polymers and their blends showed high cytocompatibility with respect to the NG108-15 neuronal cell line.…”

Section: Introductionmentioning

confidence: 99%

Medium chain length polyhydroxyalkanoates as potential matrix materials for peripheral nerve regeneration

Nigmatullin

Taylor

Basnett

et al. 2023

Regenerative Biomaterials

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Polyhydroxyalkanoates are natural, biodegradable, thermoplastic and sustainable polymers with a huge potential in fabrication of bioresorbable implantable devices for tissue engineering. We describe a comparative evaluation of three medium chain length Polyhydroxyalkanoates (mcl-PHAs), namely poly(3-hydroxyoctanoate) (P(3HO)), poly(3-hydroxyoctanoate-co-3-hydoxydecanoate) (P(3HD-co-3HO)) and poly(3-hydroxyoctanoate-co-3-hydroxydecanoate-co-3-hydroxydodecanoate), P(3HO-co-3HD-co-3HDD), one short chain length Polyhydroxyalkanoate, poly(3-hydroxybutyrate), P(3HB) and synthetic aliphatic polyesters (polycaprolactone and polylactide) with a specific focus on nerve regeneration, due to mechanical properties of mcl-PHAs closely matching nerve tissues. In vitro biological studies with NG108-15 neuronal cell and primary Schwann cells did not show a cytotoxic effect of the materials on both cell types. All mcl-PHAs supported cell adhesion and viability. Among the three mcl-PHAs, P(3HO-co-3HD) exhibited superior properties with regards to numbers of cells adhered and viable cells for both cell types, number of neurite extensions from NG108-15 cells, average length of neurite extensions and Schwann cells. Although, similar characteristics were observed for flat P(3HB) surfaces, high rigidity of this biomaterial, and FDA approved polymers such PLLA, limits their applications in peripheral nerve regeneration. Therefore, we have designed, synthesized and evaluated these materials for nerve tissue engineering and regenerative medicine, the interaction of mcl-PHAs with neuronal and Schwann cells, identifying mcl-PHAs as excellent materials to enhance nerve regeneration and potentially their clinical application in peripheral nerve repair.

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Aligned Polyhydroxyalkanoate Blend Electrospun Fibers as Intraluminal Guidance Scaffolds for Peripheral Nerve Repair

Cited by 13 publications

References 47 publications

One-Pot Assembly of Drug-Eluting Silk Coatings with Applications for Nerve Regeneration

One-Pot Assembly of Drug-Eluting Silk Coatings with Applications for Nerve Regeneration

Aminosilane Functionalized Aligned Fiber PCL Scaffolds for Peripheral Nerve Repair

Medium chain length polyhydroxyalkanoates as potential matrix materials for peripheral nerve regeneration

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