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. Author manuscript; available in PMC: 2016 Jan 31.
Published in final edited form as: Prog Neurobiol. 2014 Nov 22;0:1–25. doi: 10.1016/j.pneurobio.2014.11.003

Table 7.

Critical requirements which have not yet been met by current in vitro tissue models. Amy Hopkins, Elise DeSimone, Karolina Chwalek and David Kaplan, Progress in Neurobiology.

Biomaterials
Requirement Justification Remaining Challenges
Development of “smart” biomaterials which maintain previous biochemical characteristics (e.g. bioactivity, optical clarity, electrical conductance, etc.) without introducing cytotoxicity To make the platform more compatible with functional assays such as stimulation with light (photo-catalyzed release of compounds, live-culture imaging) and electricity (electrical stimulation of neurons) while maintaining viability Introducing favorable biochemical characteristics in “smart” polymers that frequently exhibit cytotoxic fabrication techniques; or, Optimizing physical characteristics of existing biopolymers for functional testing
Cellular Sources
Requirement Justification Remaining Challenges
Use of stem cells and iPSCs The expandability of stem or stem-like cells combined with high control over genotype and phenotype is required to reach high cell densities, achieve appropriate number of replicates and imitate human phenotype Verified protocols for expansion, differentiation, and maintaining differentiated state in long-term cultures; Optimized growth and differentiation in 3D
Designing 3D Space
Requirement Justification Remaining Challenges
High spatial control combined with gentle processing methods Neural processes such as synaptic targeting are high resolution and high sensitivity Optimizing seeding protocols to be compatible with fragile cells and proteins
Functional Evaluation
Requirement Justification Remaining Challenges
Development of methods of functional evaluation which are compatible with 3D in vitro systems including electrophysiological and imaging Relevant functional outputs are necessary for validation of tissue model Resolving and interpreting extracellular recordings to the low density, 3D cultures; High spatial control for probing electrodes; Ability to measure through thick tissue constructs (e.g. penetration of electrodes)

iPSCs = induced pluripotent stem cells