Water-responsive 4D printing based on self-assembly of hydrophobic protein “Zein” for the control of degradation rate and drug release

Zhang, Yubei; Raza, Ali; Xue, Yi; Yang, Ganggang; Hayat, Uzma; Yu, Jingwen; Liu, Chang; Wang, Huajie; Wang, Jin‐Ye

doi:10.1016/j.bioactmat.2022.11.009

Cited by 19 publications

(19 citation statements)

References 57 publications

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“…The potential benefits of such devices include improved drug delivery efficacy and reduced side effects [83]. For instance, Zhang et al [84] presented a method for 4D printing using zein plant protein gel and a specialized layered-Carbopol support bath with varying water concentrations. This printing process altered constructs' functions over time through changes to hydrophobic and hydrogen bonding.…”

Section: D Printed Responsive Devicesmentioning

confidence: 99%

“…When printed in support baths with higher water content, the constructs showed increased drug loading, quicker drug release, and degradation. The study also evaluated the biomedical efficacy of these constructs as drug-delivery systems and nerve conduits, which have been shown to be effective as drug-eluting urethral stents in a porcine model [84]. Moreover, a multiresponsive structure is created using 4D bioprinting based on SLA, which employs stress-induced shape transformation to achieve 4D reprogramming.…”

Section: D Printed Responsive Devicesmentioning

confidence: 99%

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Recent advances and future directions of 3D to 6D printing in brain cancer treatment and neural tissue engineering

et al. 2023

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The field of neural tissue engineering has undergone a revolution due to advancements in 3D printing technology. This technology now enables the creation of intricate neural tissue constructs with precise geometries, topologies, and mechanical properties. Currently, there are various 3D printing techniques available, such as stereolithography and digital light processing, and a wide range of materials can be utilized, including hydrogels, biopolymers, and synthetic materials. Furthermore, the development of 4D printing has gained traction, allowing for the fabrication of structures that can change shape over time using techniques such as shape-memory polymers. These innovations have the potential to facilitate neural regeneration, drug screening, disease modeling, and hold tremendous promise for personalized diagnostics, precise therapeutic strategies against brain cancers. This review paper provides a comprehensive overview of the current state-of-the-art techniques and materials for 3D printing in neural tissue engineering and brain cancer. It focuses on the exciting possibilities that lie ahead, including the emerging field of 4D printing. Additionally, the paper discusses the potential applications of 5D and 6D printing, which integrate time and biological functions into the printing process, in the fields of neuroscience.

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Section: D Printed Responsive Devicesmentioning

confidence: 99%

Section: D Printed Responsive Devicesmentioning

confidence: 99%

Recent advances and future directions of 3D to 6D printing in brain cancer treatment and neural tissue engineering

et al. 2023

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“…Drug-loaded scaffolds capable of sustained drug release are required to address these issues. Zein, a protein extracted from maize, has significant potential for drug delivery in various applications due to its biocompatibility and safety. , Additionally, zein delivery systems increase the bioavailability, stability, and bioactivity of drugs, particularly hydrophobic drugs, through sustained drug release and protection. − Zein-based composites have been used as biomaterials for bone regeneration for decades. For example, a zein-based scaffold was used for periodontal regeneration and proved to be biocompatible .…”

Section: Introductionmentioning

confidence: 99%

Bosutinib Laden Three-Dimensional Printed Zein Scaffolds Promote Osteogenesis

Zou,

Yin,

Lei

et al. 2024

ACS Appl. Polym. Mater.

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Bone defect repair remains a challenge to be addressed in clinical practice, and existing bone grafting methods still have disadvantages and limitations. Drugs or cytokines laden into bioactive scaffolds to promote bone regeneration is a promising strategy to deal with the problem; thus, it is meaningful to develop drugs and scaffolds with osteogenic abilities. Drug repurposing is an admirable method to find unknown usages of old drugs for enhancing osteogenic differentiation. In this study, by screening an approved drug library consisting of 2040 compounds, bosutinib, a tyrosine kinase inhibitor, was identified to promote osteogenic differentiation in vitro. The observed effect was further confirmed using polymerase chain reaction (PCR), western blot, Alizarin Red staining, and alkaline phosphatase (ALP) activity staining. Subsequently, transcriptome sequencing was performed to elucidate the osteogenesis mechanism of bosutinib, and a potential target gene, Storkhead box 1 (STOX1), which was not reported to be associated with osteogenesis, was found. By a gene knockdown strategy, we provided preliminary evidence that bosutinib can promote osteogenic differentiation by mediating STOX1. Furthermore, in order to maximize the local effects of drug and minimize its side effects, a bosutinib laden three-dimensional (3D)-printed zein scaffold was constructed and characterized, and its ability of promoting osteogenesis was evaluated in vivo. Micro-CT analysis and histological staining demonstrated that the scaffold effectively promoted bone regeneration. All in all, our study provides a therapeutic option for the treatment of bone defects.

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“…In the field of additive manufacturing (3D-printing) the thermoplasticity of zein has been exploited in fused deposition modelling (FDM) where zein is melted and extruded through a nozzle [ 13 , 14 ]. Additionally, ethanolic zein solutions have been used for 3D bioprinting [ 15 ] and for 4D printing in drug release applications [ 16 ]. The tailorability of zein, as evidenced in various studies, has facilitated its broader application.…”

Section: Introductionmentioning

confidence: 99%

Conformations of a highly expressed Z19 α-zein studied with AlphaFold2 and MD simulations

Christensen

2024

PLoS ONE

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α-zeins are amphiphilic maize seed storage proteins with material properties suitable for a multitude of applications e.g., in renewable plastics, foods, therapeutics and additive manufacturing (3D-printing). To exploit their full potential, molecular-level insights are essential. The difficulties in experimental atomic-resolution characterization of α-zeins have resulted in a diversity of published molecular models. However, deep-learning α-zein models are largely unexplored. Therefore, this work studies an AlphaFold2 (AF2) model of a highly expressed α-zein using molecular dynamics (MD) simulations. The sequence of the α-zein cZ19C2 gave a loosely packed AF2 model with 7 α-helical segments connected by turns/loops. Compact tertiary structure was limited to a C-terminal bundle of three α-helices, each showing notable agreement with a published consensus sequence. Aiming to chart possible α-zein conformations in practically relevant solvents, rather than the native solid-state, the AF2 model was subjected to MD simulations in water/ethanol mixtures with varying ethanol concentrations. Despite giving structurally diverse endpoints, the simulations showed several patterns: In water and low ethanol concentrations, the model rapidly formed compact globular structures, largely preserving the C-terminal bundle. At ≥ 50 mol% ethanol, extended conformations prevailed, consistent with previous SAXS studies. Tertiary structure was partially stabilized in water and low ethanol concentrations, but was disrupted in ≥ 50 mol% ethanol. Aggregated results indicated minor increases in helicity with ethanol concentration. β-sheet content was consistently low (∼1%) across all conditions. Beyond structural dynamics, the rapid formation of branched α-zein aggregates in aqueous environments was highlighted. Furthermore, aqueous simulations revealed favorable interactions between the protein and the crosslinking agent glycidyl methacrylate (GMA). The proximity of GMA epoxide carbons and side chain hydroxyl oxygens simultaneously suggested accessible reactive sites in compact α-zein conformations and pre-reaction geometries for methacrylation. The findings may assist in expanding the applications of these technologically significant proteins, e.g., by guiding chemical modifications.

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Water-responsive 4D printing based on self-assembly of hydrophobic protein “Zein” for the control of degradation rate and drug release

Cited by 19 publications

References 57 publications

Recent advances and future directions of 3D to 6D printing in brain cancer treatment and neural tissue engineering

Recent advances and future directions of 3D to 6D printing in brain cancer treatment and neural tissue engineering

Bosutinib Laden Three-Dimensional Printed Zein Scaffolds Promote Osteogenesis

Conformations of a highly expressed Z19 α-zein studied with AlphaFold2 and MD simulations

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