Microscale Architecture in Biomaterial Scaffolds for Spatial Control of Neural Cell Behavior

Abstract

Biomaterial scaffolds mimic aspects of the native central nervous system (CNS) extracellular matrix (ECM) and have been extensively utilized to influence neural cell (NC) behavior in in vitro and in vivo settings. These biomimetic scaffolds support NC cultures, can direct the differentiation of NCs, and have recapitulated some native NC behavior in an in vitro setting. However, NC transplant therapies and treatments used in animal models of CNS disease and injury have not fully restored functionality. The observed lack of functional recovery occurs despite improvements in transplanted NC viability when incorporating biomaterial scaffolds and the potential of NC to replace damaged native cells. The behavior of NCs within biomaterial scaffolds must be directed in order to improve the efficacy of transplant therapies and treatments. Biomaterial scaffold topography and imbedded bioactive cues, designed at the microscale level, can alter NC phenotype, direct migration, and differentiation. Microscale patterning in biomaterial scaffolds for spatial control of NC behavior has enhanced the capabilities of in vitro models to capture properties of the native CNS tissue ECM. Patterning techniques such as lithography, electrospinning and three-dimensional (3D) bioprinting can be employed to design the microscale architecture of biomaterial scaffolds. Here, the progress and challenges of the prevalent biomaterial patterning techniques of lithography, electrospinning, and 3D bioprinting are reported. This review analyzes NC behavioral response to specific microscale topographical patterns and spatially organized bioactive cues.

Self-Assembling Hydrogel Structures for Neural Tissue Repair

“… 170 , 171 This cellular response is highly desirable for neural regeneration, and methods to create a material that elicits this cellular response in clinical applications are of utmost interest. 10 , 172 …”

“…Similarly, human induced pluripotent stem cells (hiPSCs) can be differentiated into neuronal lineages when exposed to aligned microgrooves . This property can be exploited as a powerful method to control and tune the development of a neural progenitor cell population, and guide its growth at the same time. , This cellular response is highly desirable for neural regeneration, and methods to create a material that elicits this cellular response in clinical applications are of utmost interest. , …”

An Electroactive Oligo‐EDOT Platform for Neural Tissue Engineering

“…To prepare constructs suitable for further processing and scaffold fabrication, we selected PCL as a suitable co-polymer, due to its biodegradable properties and well-established use in tissue engineering. Boc-protected dimer (5), tetramer (7), and pentamer (8) oligoEDOTs were deprotected under acidic conditions to yield the free amines (9, 11, and 12 respectively), ( Figure S1, Supporting Information). Ring-opening polymerization of ε-caprolactone was then undertaken using the amino-oligoEDOT as a macroinitiator (Figures 1b and 2a).…”

“…Advances in bio‐fabrication technologies have led to promising developments in specialized 3D architectures for neural tissue engineering, including 3D scaffolds with microscale or nanoscale topography to guide cellular interactions. [ 7–11 ] Techniques such as electrospinning have been used to create biomimetic fibrous matrices which have successfully been applied for the growth of neural networks, as suitably aligned nanoscale fibers can provide directionality for the growth of neurons. [ 9,12–17 ] More recently, melt electrospinning writing (MEW) has emerged as a promising method to deposit highly defined fibrous scaffolds.…”

Biofunctional Silk Kirigami With Engineered Properties

“…[11][12] Across length scales, micropatterned and microstructured materials may be used for cell co-cultures and spatial control. [13][14][15] Recently, approaches building on principles borrowed from the Japanese paper arts such as origami and kirigami, have shown great promise. 16 Origami refers to folding ("ori-"), whereas kirigami involves cutting ("kiri-") of paper ("-gami").…”