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Evaluating Complexity in Orthopedic Tissue-on-a-Chip Systems.

Hannah M Zlotnick¹, Declan N Goddard^1,2, Jason A Burdick^1,2

¹BioFrontiers Institute, University of Colorado Boulder, Boulder, CO, 80303, USA.

Advanced Healthcare Materials

|November 19, 2025

Summary

This summary is machine-generated.

Orthopedic tissue-on-a-chip systems model disease and screen drugs. Increased complexity in these systems, while improving physiological mimicry, reduces experimental throughput, highlighting a key development tradeoff.

Keywords:

microphysiological model musculoskeletal orthopedic tissue‐on‐a‐chip

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Area of Science:

Biomedical Engineering
Regenerative Medicine
Tissue Engineering

Background:

Orthopedic tissue-on-a-chip systems are advancing disease modeling and therapeutic screening.
Platform complexity influences physiological mimicry and experimental throughput.

Purpose of the Study:

To systematically review and analyze the complexity of current orthopedic tissue-on-a-chip systems.
To develop a quantitative scoring system to compare system complexity.
To guide future orthopedic tissue-on-a-chip system development.

Main Methods:

Systematic literature search to create a publication library.
Summarization of device components (cells, materials, structures, stimuli) and applications.
Development and application of a quantitative scoring system for complexity analysis.

Main Results:

Most platforms utilize polydimethylsiloxane (PDMS), human cells, and natural hydrogels with limited tissue structures and stimuli.
Multi-tissue systems exhibit greater complexity in assembly, cellular components, and materials.
A negative correlation exists between system complexity and experimental throughput.

Conclusions:

Future orthopedic tissue-on-a-chip systems require balancing complexity with throughput for efficient data acquisition.
The developed scoring system aids in evaluating and comparing system complexity.
Findings provide a framework for designing advanced, clinically relevant orthopedic tissue models.