Blood–brain barrier (BBB)-on-a-chip: a promising breakthrough in brain disease research DOI
Bo Peng,

Shiping Hao,

Ziqiu Tong

et al.

Lab on a Chip, Journal Year: 2022, Volume and Issue: 22(19), P. 3579 - 3602

Published: Jan. 1, 2022

The blood-brain barrier (BBB) represents a key challenge in developing brain-penetrating therapeutic molecules. BBB dysfunction is also associated with the onset and progression of various brain diseases. BBB-on-a-chip (μBBB), an organ-on-chip technology, has emerged as powerful vitro platform that closely mimics human microenvironments. While μBBB technology seen wide application study cancer, its utility other disease models ("μBBB+") less appreciated. Based on advances evolution for diseases over last decade, we propose concept "μBBB+" system summarize major promising applications pathological studies, personalized medical research, drug development, multi-organ-on-chip approaches. We believe such sophisticated highly tunable further advancement understanding

Language: Английский

Microfluidic Devices: A Tool for Nanoparticle Synthesis and Performance Evaluation DOI Creative Commons
Sara Gimondi, Helena Ferreira, Rui L. Reis

et al.

ACS Nano, Journal Year: 2023, Volume and Issue: 17(15), P. 14205 - 14228

Published: July 27, 2023

The use of nanoparticles (NPs) in nanomedicine holds great promise for the treatment diseases which conventional therapies present serious limitations. Additionally, NPs can drastically improve early diagnosis and follow-up many disorders. However, to harness their full capabilities, they must be precisely designed, produced, tested relevant models. Microfluidic systems simulate dynamic fluid flows, gradients, specific microenvironments, multiorgan complexes, providing an efficient cost-effective approach both synthesis screening. technologies allow under controlled conditions, enhancing batch-to-batch reproducibility. Moreover, due versatility microfluidic devices, it is possible generate customize endless platforms rapid vitro vivo screening NPs' performance. Indeed, devices show potential as advanced small organism manipulation immobilization. In this review, first we summarize major that synthesis. Next, will discuss most innovative enable mimicking environments well give insights into organism-on-a-chip promising application We conclude review with a critical assessment current challenges future directions impact field nanomedicine.

Language: Английский

Citations

124

A predictive microfluidic model of human glioblastoma to assess trafficking of blood–brain barrier-penetrant nanoparticles DOI Creative Commons
Joelle P. Straehla, Cynthia Hajal, Hannah C. Safford

et al.

Proceedings of the National Academy of Sciences, Journal Year: 2022, Volume and Issue: 119(23)

Published: June 1, 2022

The blood–brain barrier represents a significant challenge for the treatment of high-grade gliomas, and our understanding drug transport across this critical biointerface remains limited. To advance preclinical therapeutic development there is an urgent need predictive in vitro models with realistic blood–brain-barrier vasculature. Here, we report vascularized human glioblastoma multiforme (GBM) model microfluidic device that accurately recapitulates brain tumor vasculature self-assembled endothelial cells, astrocytes, pericytes to investigate targeted nanotherapeutics into GBM cells. Using modular layer-by-layer assembly, functionalized surface nanoparticles GBM-targeting motifs improve trafficking tumors. We directly compared nanoparticle platform mouse capillaries using intravital imaging, validating ability vivo transport. investigated potential by encapsulating cisplatin showed improved efficacy these GBM-targeted both orthotopic xenograft model. Our biomaterials advance, enabling in-depth investigation accelerating nanotherapeutics.

Language: Английский

Citations

86

Breaking the resolution limits of 3D bioprinting: future opportunities and present challenges DOI Creative Commons
Tommaso Zandrini,

Sammy Florczak,

Riccardo Levato

et al.

Trends in biotechnology, Journal Year: 2022, Volume and Issue: 41(5), P. 604 - 614

Published: Dec. 10, 2022

Bioprinting aims to produce 3D structures from which embedded cells can receive mechanical and chemical stimuli that influence their behavior, direct organization migration, promote differentiation, in a similar way what happens within the native extracellular matrix. However, limited spatial resolution has been bottleneck for conventional bioprinting approaches. Reproducing fine features at cellular scale, while maintaining reasonable printing volume, is necessary enable biofabrication of more complex functional tissue organ models. In this opinion article we recount emergence of, discuss most promising, high-definition (HD) techniques achieve goal, discussing obstacles remain be overcome, applications are envisioned engineering field.

Language: Английский

Citations

74

Landscape of human organoids: Ideal model in clinics and research DOI Creative Commons
Xinxin Han, Chunhui Cai, Wei Deng

et al.

The Innovation, Journal Year: 2024, Volume and Issue: 5(3), P. 100620 - 100620

Published: April 1, 2024

In the last decade, organoid research has entered a golden era, signifying pivotal shift in biomedical landscape. The year 2023 marked milestone with publication of thousands papers this arena, reflecting exponential growth. However, amid burgeoning expansion, comprehensive and accurate overview field been conspicuously absent. Our review is intended to bridge gap, providing panoramic view rapidly evolving We meticulously analyze from eight distinctive vantage points, harnessing our rich experience academic research, industrial application, clinical practice. present deep exploration advances technology, underpinned by long-standing involvement arena. narrative traverses historical genesis organoids their transformative impact across various sectors, including oncology, toxicology, drug development. delve into synergy between avant-garde technologies such as synthetic biology single-cell omics discuss role tailoring personalized medicine, enhancing high-throughput screening, constructing physiologically pertinent disease models. analysis reflective discourse provide dive existing landscape emerging trends technology. spotlight technological innovations, methodological evolution, broadening spectrum applications, emphasizing revolutionary influence discovery, other fields. Looking ahead, we cautiously anticipate future developments especially its potential implications for patient care, new avenues research. trust that will be an asset researchers, clinicians, patients keen interest medical strategies. offer broad prospective capabilities encompassing wide range current applications. summary, attempt field. reflections, summaries, projections might useful researchers hope contribute shaping trajectory dynamic advancing

Language: Английский

Citations

34

Multifunctional Nanotheranostics for Overcoming the Blood–Brain Barrier DOI
M H Miran Beygi, Fatemeh Oroojalian, Soheil Azizi‐Arani

et al.

Advanced Functional Materials, Journal Year: 2024, Volume and Issue: 34(19)

Published: Jan. 4, 2024

Abstract The blood–brain barrier (BBB) is a tailored system of capillary endothelial cells intermixed with tight junctions and adherent that regulates the transport various materials substances between blood vasculature central nervous (CNS). However, in cases brain diseases, BBB's protective regulatory effects hamper therapeutics from reaching affected sites sufficient quantities. This has so far been leading challenge treating CNS diseases disorders. For this problem to be overcome, recent research sought develop novel modalities achieve efficient therapy alleviate associated symptoms. Therefore, numerous strategies have operated years address limitations traditional invasive methods, including poor penetration serious side effects. As desperately in‐demand technology, nanotheranostics particularly shown promising results. Herein, review reports advancements techniques nanotechnology‐based developed for neurodegenerative study provides comprehensive data on subject used future studies management disorders diseases.

Language: Английский

Citations

26

Interstitial Flow Promotes the Formation of Functional Microvascular Networks In Vitro through Upregulation of Matrix Metalloproteinase‐2 DOI Creative Commons
Shun Zhang, Zhengpeng Wan, Georgios Pavlou

et al.

Advanced Functional Materials, Journal Year: 2022, Volume and Issue: 32(43)

Published: Aug. 15, 2022

Self-organized microvascular networks (MVNs) have become key to the development of many microphysiological models. However, self-organizing nature this process combined with variations between types or batches endothelial cells (ECs) often lead inconsistency failure form functional MVNs. Since interstitial flow (IF) has been reported play a beneficial role in angiogenesis, vasculogenesis, and 3D capillary morphogenesis, we systematically investigated IF plays during neovessel formation customized single channel microfluidic chip for which fully characterized. Compared static conditions, MVNs formed under higher vessel density diameters greater network perfusability. Through series inhibitory experiments, demonstrated that treatment improves vasculogenesis by ECs through upregulation matrix metalloproteinase-2 (MMP-2). We then successfully implemented novel strategy involving interplay MMP-2 inhibitor regulate morphological parameters self-organized MVNs, vascular permeability perfusability well maintained. The revealed mechanism proposed methodology were further validated brain MVN model. Our findings methods potential be widely utilized boost various organotypic could incorporated into related bioengineering applications where perfusable vasculature is desired.

Language: Английский

Citations

53

Organ‐On‐A‐Chip Models of the Blood–Brain Barrier: Recent Advances and Future Prospects DOI
Satoru Kawakita, Kalpana Mandal, Lei Mou

et al.

Small, Journal Year: 2022, Volume and Issue: 18(39)

Published: Aug. 17, 2022

The human brain and central nervous system (CNS) present unique challenges in drug development for neurological diseases. One major obstacle is the blood-brain barrier (BBB), which hampers effective delivery of therapeutic molecules into while protecting it from blood-born neurotoxic substances maintaining CNS homeostasis. For BBB research, traditional vitro models rely upon Petri dishes or Transwell systems. However, these static lack essential microenvironmental factors such as shear stress proper cell-cell interactions. To this end, organ-on-a-chip (OoC) technology has emerged a new modeling approach to better recapitulate highly dynamic vivo microenvironment so-called neural vascular unit (NVU). Such BBB-on-a-chip have made substantial progress over last decade, concurrently there been increasing interest various diseases Alzheimer's disease Parkinson's using OoC technology. In addition, with recent advances other scientific technologies, several opportunities improve platform via multidisciplinary approaches are available. review, an overview NVU provided, applications personalized medicine discovery discussed, current future directions delineated.

Language: Английский

Citations

51

Microfluidic trends in drug screening and drug delivery DOI Open Access
Jianguo Feng, Jiřı́ Neužil, A. Manz

et al.

TrAC Trends in Analytical Chemistry, Journal Year: 2022, Volume and Issue: 158, P. 116821 - 116821

Published: Nov. 14, 2022

Language: Английский

Citations

48

A Robust Method for Perfusable Microvascular Network Formation In Vitro DOI
Zhengpeng Wan, Amy X. Zhong, Shun Zhang

et al.

Small Methods, Journal Year: 2022, Volume and Issue: 6(6)

Published: April 3, 2022

Micropost-based microfluidic devices are widely used for microvascular network (MVN) formation in diverse research fields. However, consistently generating perfusable MVNs of physiological morphology and dimension has proven to be challenging. Here, how initial seeding parameters determine key characteristics MVN is investigated a robust two-step strategy generate established.

Language: Английский

Citations

42

Micro/nanosystems for controllable drug delivery to the brain DOI Creative Commons

Mingzhen Tian,

Zhichao Ma, Guang‐Zhong Yang

et al.

The Innovation, Journal Year: 2023, Volume and Issue: 5(1), P. 100548 - 100548

Published: Nov. 27, 2023

•Micro/nanosystems show their potential to address the challenges of precise drug delivery brain.•Microfluidic platforms enable creation biomimetic in vitro brain models.•Micro/nano materials is emerging as a key player controllable delivery.•The minimally invasive fiberbot microsystem reduces procedure's invasiveness.•Image tracking micro/nanosystems allows for controlled therapeutic interventions. Drug crucial treatment central nervous system disorders. While significant progress has been made recent years, there are still major achieving brain. Unmet clinical needs arise from various factors, including transport, handling large doses, methods crossing biological barriers, use imaging guidance, and effective models analyzing delivery. Recent advances have shown promise addressing some these challenges. These include utilization microfluidic test validate process setting, development novel micro/nanocarriers loads across blood-brain barrier, implementation micro-intervention systems delivering drugs through intraparenchymal or peripheral routes. In this article, we present review latest developments We also delve into relevant diseases, conventional methods. addition, discuss future prospects robotic equipped with directed transportation, real-time image closed-loop control.

Language: Английский

Citations

35