a-microfluidic-technique-to-probe-cell-deformability

A Microfluidic Technique to Probe Cell Deformability

Here we detail the design, fabrication, and use of a microfluidic device to evaluate the deformability of a large number of individual cells in an ...

University of California, Los Angeles

University of Notre Dame

This work aims to facilitate the transition of micro-robotic deposition (microRD) technology from the research bench to a mass manufacturing environment. The bone scaffolding application is targeted; however, the evaluation process developed is applicable to multiple colloidal material systems, length scales, and structure architectures. A design of experiments (DoE) approach is used to develop statistical correlations between three manufacturing treatments (material calcination time, nozzle size, and deposition speed) and defined reliability metrics. All three selected treatments have a significant effect on structure quality. A longer material calcination time improves the deposition of internal features. Logically, a larger nozzle size decreases structural defects. However, an unexpected result is revealed by this study. Higher deposition speeds are shown to either significantly improve or have no effect on structure quality, permitting a decrease in manufacturing time without adverse consequences.

Micro-robotic deposition guidelines by a design of experiments approach to maximize fabrication reliability for the bone scaffold application.

It is well established that scaffolds for applications in bone tissue engineering require interconnected pores on the order of 100 microm for bone in growth and nutrient and waste transport. As a result, most studies have focused on scaffold macroporosity (>100 microm). More recently researchers have investigated the role of microporosity in calcium phosphate -based scaffolds. Osteointegration into macropores improves when scaffold rods or struts contain micropores, typically defined as pores less than approximately 50 microm. We recently demonstrated multiscale osteointegration, or growth into both macropores and intra-red micropores (<10 microm), of biphasic calcium phosphate (BCP) scaffolds. The combined effect of BMP-2, a potent osteoinductive growth factor, and multiscale porosity has yet to be investigated. In this study we implanted BCP scaffolds into porcine mandibular defects for 3, 6, 12 and 24 weeks and evaluated the effect of BMP-2 on multiscale osteointegration. The results showed that given this in vivo model BMP-2 influences osteointegration at the microscale, but not at the macroscale, but not at the macroscale. Cell density was higher in the rod micropores for scaffolds containing BMP-2 compared with controls at all time points, but BMP-2 was not required for bone formation in micropores. In contrast, there was essentially no difference in the fraction of bone in macropores for scaffolds with BMP-2 compared with controls. Additionally, bone in macropores seemed to have reached steady-state by 3 weeks. Multiscale osteointegration results in bone-scaffold composites that are fully osteointegrated, with no 'dead space'. These composites are likely to contain a continuous cell network as well as the potential for enhanced load transfer and improved mechanical properties.

The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity.

It is well known that pore design is an important determinant of both the quantity and distribution of regenerated bone in artificial bone tissue scaffolds. A requisite feature is that scaffolds must contain pore interconnections on the order of 100-1000 μm (termed macroporosity). Within this range, there is not a definitive optimal interconnection size. Recent results suggest that pore interconnections permeating the scaffold build material on the order of 2-20 μm (termed microporosity) drive bone growth into the macropore space at a faster rate and also provide a new space for bone growth, proliferating throughout the interconnected microporous network. The effects of microstructural features on bone growth has yet to be fully understood. This work presents the manufacture and characterization of novel combinatorial test scaffolds, scaffolds that test multiple microporosity and macroporosity designs within a single scaffold. Scaffolds such as this can efficiently evaluate multiple mechanical designs, with the advantage of having the designs colocated within a single defect site and therefore less susceptible to experimental variation. This paper provides the manufacturing platform, manufacturing control method, and demonstrates the manufacturing capabilities with three representative scaffolds.

Article	Year
Micro-robotic deposition guidelines by a design of experiments approach to maximize fabrication reliability for the bone scaffold application. Acta biomaterialia\| PubMed ID: 18378507	2008
The effect of BMP-2 on micro- and macroscale osteointegration of biphasic calcium phosphate scaffolds with multiscale porosity. Acta biomaterialia\| PubMed ID: 20176148	2010
Design and manufacture of combinatorial calcium phosphate bone scaffolds. Journal of biomechanical engineering\| PubMed ID: 22070326	2011

David J. Hoelzle

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