Abstract

The fertilised chick egg and particularly its chorioallantoic membrane (CAM) have drawn continuing interest in biomedicine and bioengineering fields, especially for research on vascular study, cancer, drug screening and development, cell factors, stem cells, etc. This literature review systemically introduces the CAM’s structural evolution, functions, vascular features and the circulation system, and cell regulatory factors. It also presents the major and updated applications of the CAM in assays for pharmacokinetics and biodistribution, drug efficacy and toxicology testing/screening in preclinical pharmacological research. The time course of CAM applications for different assays and their advantages and limitations are summarised. Among these applications, two aspects are emphasised: (1) potential utility of the CAM for preclinical studies on vascular-disrupting agents (VDAs), promising for anti-cancer vascular-targeted therapy, and (2) modern imaging technologies, including modalities and their applications for real-time visualisation, monitoring and evaluation of the changes in CAM vasculature as well as the interactions occurring after introducing the tested medical, pharmaceutical and biological agents into the system. The aim of this article is to help those working in the biomedical field to familiarise themselves with the chick embryo CAM as an alternative platform and to utilise it to design and optimise experimental settings for their specific research topics.

Highlights

  • Introduction iationsTo produce new medications which are safe and efficacious, and can pass all regulatory requirements, pharmaceutical development must proceed through several stages: (1)drug candidate discovery, (2) molecule characterisation, (3) formulation for delivery, (4)pharmacokinetics and biodistribution, (5) efficacy and toxicology testing, (6) investigational new drug (IND) application, (7) bioanalytical testing and (8) phase I–IV clinical trials.The intermediate in vivo preclinical studies of the above stages 4 and 5 are traditionally conducted, by the laboratories of academia or industry, on experimental animals without and with human disease simulation

  • Becomesto increasingly large,membrane the two extra-embryonic circulations larised membrane serves as the respiratory system of the embryo and is solely responsible remain separate, but both are connected to the intra-embryonic circulation

  • Vessel permeability provides an important feature to study the pharmacokinetics of drug diffusion through the chorioallantoic membrane (CAM) vasculature, while the change in vascular leakage in the CAM can be monitored at different development phases, for example during endothelial proliferation, cytodifferentiation and senescence of the chick embryo

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Summary

Development of Fertilised Chick Eggs in Incubation

The chick embryo normally experiences 21 days of development before hatching, which corresponds to multiple stages (Figure 1).

The starts in thestarts chickinegg
CAM Development and Physiological Function
Microcirculation and CAM
Growth and Regulation Factors of Angiogenesis in CAM
CAM Assays in Preclinical Biomedical and Pharmacological Research
Drug Delivery System
Conventional Analysis Approach
Advanced Approaches
Vessel Permeability
Biocompatibility
The Efficacy of Drugs
Pro-Angiogenic Agents
Anti-Angiogenic Agents
Wound Healing
Tumour angiogenesis and growth
Tumour metastasis
Drug assays
Irritation
Toxicity
Anti-Vascular Selectivity
Tubulin-binding agents
Flavonoids
Test Methods
Drug Tests
Vascular Assays
Tumour Implantation
Cell Growth Factors and Antibody Inhibitors
Methods to Image and Evaluate the Changes in the Vasculature of the CAM
Light Microscopic Methods
X-ray Methods
Magnetic Resonance Methods
Methods
Acoustic Methods
Optical Techniques and Methods
Laser Doppler Principle
Findings
Laser Speckle Principle
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