Development of a regenerative porous PLCL nerve guidance conduit with swellable hydrogel-based microgrooved surface pattern via 3D printing

Lee, Hyun Su; Jeon, Eun Young; Nam, Jae Jun; Park, Ji Hun; Choi, In Cheul; Kim, Soo Hyun; Chung, Justin J.; Lee, Kangwon; Park, Jong Woong; Jung, Youngmee

doi:10.1016/j.actbio.2022.01.042

Cited by 44 publications

(25 citation statements)

References 48 publications

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“…Recently, in addition to structural support, biophysical considerations in the rational design of biomaterials and biointerfaces have been shown to direct cell guidance, cell signaling, and cell fate. 93,94 Similar to our study, previous reports have presented promising results in controlling cellular responses and cell fate through topography instead of conventional biochemical induction. 95 These designs based on cell−substrate interactions can be integrated into implantable biomedical devices and microfluidics devices, to fine-tune the control of cell proliferation, differentiation, tissue integration, and thus the overall performance.…”

Section: Discussionsupporting

confidence: 84%

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

Hsu

Serio

Gopal

et al. 2022

ACS Appl. Mater. Interfaces

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A number of studies have recently shown how surface topography can alter the behavior and differentiation patterns of different types of stem cells. Although the exact mechanisms and molecular pathways involved remain unclear, a consistent portion of the literature points to epigenetic changes induced by nuclear remodeling. In this study, we investigate the behavior of clinically relevant neural populations derived from human pluripotent stem cells when cultured on polydimethylsiloxane microgrooves (3 and 10 μm depth grooves) to investigate what mechanisms are responsible for their differentiation capacity and functional behavior. Our results show that microgrooves enhance cell alignment, modify nuclear geometry, and significantly increase cellular stiffness, which we were able to measure at high resolution with a combination of light and electron microscopy, scanning ion conductance microscopy (SICM), and atomic force microscopy (AFM) coupled with quantitative image analysis. The microgrooves promoted significant changes in the epigenetic landscape, as revealed by the expression of key histone modification markers. The main behavioral change of neural stem cells on microgrooves was an increase of neuronal differentiation under basal conditions on the microgrooves. Through measurements of cleaved Notch1 levels, we found that microgrooves downregulate Notch signaling. We in fact propose that microgroove topography affects the differentiation potential of neural stem cells by indirectly altering Notch signaling through geometric segregation and that this mechanism in parallel with topography-dependent epigenetic modulations acts in concert to enhance stem cell neuronal differentiation.

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Section: Discussionsupporting

confidence: 84%

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

Hsu

Serio

Gopal

et al. 2022

ACS Appl. Mater. Interfaces

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“…PLCL (LA/CL = 50:50) was synthesized as previously described . LA and CL were polymerized in an oil bath at 150 °C for 24 h with an initiator (1,6-hexanediol) and a catalyst (Sn(Oct) 2 ) at a molar ratio 5000:5000:1:1.…”

Section: Methodsmentioning

confidence: 99%

Effect of Electrical Stimulation on Nerve-Guided Facial Nerve Regeneration

Choe

Han

et al. 2023

ACS Biomater. Sci. Eng.

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This study aimed to investigate the effect of electrical stimulation on poly(D,L-lactide-co-ε-caprolactone) nerve guidance conduits (NGCs) in promoting the recovery of facial function and nerve regeneration after facial nerve (FN) injury in a rat model. In the experimental group, both the NGC and transcutaneous electrical nerve stimulation (ES) were used simultaneously; in the control group, only NGC was used. ES groups were divided into two groups, and direct current (DC) and charge-balanced pulse stimulation (Pulse) were applied. The ES groups showed significantly improved whisker movement than the NGC-only group. The number of myelinated neurons was higher in ES groups, and the myelin sheath was also thicker and more uniform. In addition, the expression of neurostructural proteins was also higher in ES groups than in the NGC-only group. This study revealed that FN regeneration and functional recovery occurred more efficiently when ES was applied in combination with NGCs.

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“…PNI results in the loss of sensory or motor functions, adding severe physical, psychological and economic burden on patients ( Lee et al, 2022 ). Nerve autografts remain the clinical gold standard for treating PNI; however, nerve autografts have significant limitations such as donor site morbidity, limited donor supply, and mismatch between the donor and the recipient site ( Zhang et al, 2020a ).…”

Section: Applications Of Plla-based Scaffolds In Peripheral Nerve And...mentioning

confidence: 99%

Recent advances in PLLA-based biomaterial scaffolds for neural tissue engineering: Fabrication, modification, and applications

Dai

Shao

et al. 2022

Front. Bioeng. Biotechnol.

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Repairing and regenerating injured neural tissue remains a worldwide challenge. Tissue engineering (TE) has been highlighted as a potential solution to provide functional substitutes for damaged organs or tissue. Among the biocompatible and biodegradable materials, poly-L-lactic-acid (PLLA) has been widely investigated in the TE field because of its tunable mechanical properties and tailorable surface functionalization. PLLA-based biomaterials can be engineered as scaffolds that mimic neural tissue extracellular matrix and modulate inflammatory responses. With technological advances, PLLA-based scaffolds can also have well-controlled three-dimensional sizes and structures to facilitate neurite extension. Furthermore, PLLA-based scaffolds have the potential to be used as drug-delivery carriers with controlled release. Moreover, owing to the good piezoelectric properties and capacity to carry conductive polymers, PLLA-based scaffolds can be combined with electrical stimulation to maintain stemness and promote axonal guidance. This mini-review summarizes and discusses the fabrication and modification techniques utilized in the PLLA-based biomaterial scaffolds for neural TE. Recent applications in peripheral nerve and spinal cord regeneration are also presented, and it is hoped that this will guide the future development of more effective and multifunctional PLLA-based nerve scaffolds.

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Development of a regenerative porous PLCL nerve guidance conduit with swellable hydrogel-based microgrooved surface pattern via 3D printing

Cited by 44 publications

References 48 publications

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

Biophysical Regulations of Epigenetic State and Notch Signaling in Neural Development Using Microgroove Substrates

Effect of Electrical Stimulation on Nerve-Guided Facial Nerve Regeneration

Recent advances in PLLA-based biomaterial scaffolds for neural tissue engineering: Fabrication, modification, and applications

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