Hierarchical polymeric scaffolds support the growth of MC3T3-E1 cells.

Tissue engineering makes use of the principles of biology and engineering to sustain 3D cell growth and promote tissue repair and/or regeneration. In this study, macro/microporous scaffold architectures have been developed using a hybrid solid freeform fabrication/thermally induced phase separation (TIPS) technique. Poly(lactic-co-glycolic acid) (PLGA) dissolved in 1,4-dioxane was used to generate a microporous matrix by the TIPS method. The 3D-bioplotting technique was used to fabricate 3D macroporous constructs made of polyethylene glycol (PEG). Embedding the PEG constructs inside the PLGA solution prior to the TIPS process and subsequent extraction of PEG following solvent removal (1,4-dioaxane) resulted in a macro/microporous structure. These hierarchical scaffolds with a bimodal pore size distribution (<50 and >300 µm) contained orthogonally interconnected macro-channels generated by the extracted PEG. The diameter of the macro-channels was varied by tuning the dispensing parameters of the 3D bioplotter. The in vitro cell culture using murine MC3T3-E1 cell line for 21 days demonstrated that these scaffolds could provide a favorable environment to support cell adhesion and growth.

Solvent-free polymer/bioceramic scaffolds for bone tissue engineering: fabrication, analysis, and cell growth.

This study examines the potential use of porous polycaprolactone (PCL) and polycaprolocatone/hydroxyapatite (PCL/HA) scaffolds fabricated through melt molding and porogen leaching for bone tissue engineering. While eliminating organic solvents is desirable, the process steps proposed in this study for uniformly dispersing HA particles (~5 µm in size) within the scaffold can also contribute to homogeneous properties for these porous composites. Poly(ethylene oxide) (PEO) was chosen as a porogen due to its similar density and melting point as PCL. Pore size of the scaffold was controlled by limiting the size of PCL and PEO particles used in fabrication. The percent of HA in the fabricated scaffolds was quantified by thermogravimetric analysis (TGA). Mechanical testing was used to compare the modulus of the scaffolds to that of bone, and the pore size distribution was examined with microcomputed tomography (µCT). Scanning electron microscopy (SEM) was used to examine the effect on scaffold morphology caused by the addition of HA particles. Both µCT and SEM results showed that HA could be incorporated into PCL scaffolds without negatively affecting scaffold morphology or pore formation. Energy-dispersive X-ray spectroscopy (EDS) and elemental mapping demonstrated a uniform distribution of HA within PCL/HA scaffolds. Murine calvaria-derived MC3T3-E1 cells were used to determine whether cells could attach on scaffolds and grow for up to 21 days. SEM images revealed an increase in cell attachment with the incorporation of HA into the scaffolds. Similarly, DNA content analysis showed a higher cell adhesion to PCL/HA scaffolds.

Improving the homogeneity of tissue-mimicking cryogel phantoms for medical imaging.

PURPOSE: Tissue-mimicking phantoms can help in uncovering potential weaknesses in medical imaging systems. This work presents a new approach to developing phantoms for magnetic resonance elastography (MRE). Elastography requires sufficiently large and well-characterized phantoms to accurately validate motion estimation methods and to provide accurate stiffness measurements. Physically crosslinked polyvinyl alcohol hydrogels, prepared by the freeze-thaw technique, have been extensively used as MRE phantoms. However, the large cryogels developed by this technique usually exhibit variations in properties due to the low thermal conductivity of the polymeric solution. This leads to variations in freezing-thawing rates across the gels. Therefore, designing homogeneous large cryogels with tissue-mimicking mechanical properties poses a challenge to medical imaging researchers. METHODS: Unlike conventional freeze-thaw techniques that use either sudden freezing or ramp freezing, the authors have developed a modified freeze-thaw process featuring a combination of multiple ramps and isotherms within a single freeze-thaw cycle. Aiming to develop brain-mimicking phantoms, they have blended three different water-soluble polymers (polyvinyl pyrrolidone, agarose, and polyacrylic acid) with polyvinyl alcohol and produced cryogels with a wide range of mechanical properties and swelling characteristics. The effect of the modified process on mechanical properties, swelling, and melting enthalpy of the produced gels has been investigated in this study. RESULTS: It was demonstrated that imposing additional isotherms at the vicinity of phase change temperatures could effectively reduce the variations in properties within a typical large phantom (diameter vs height: 100 mm × 100 mm). While the conventional freeze-thaw process resulted in ∼16% variation in the enthalpy of fusion across the produced gels, the modified process reduced this variation to below 8%. The homogeneity in mechanical properties was also improved by over 50% compared to the conventional process. Upon comparing the mechanical properties of the gels with those of brain white matter, the authors have shown that a blend of polyvinyl alcohol and polyvinyl pyrrolidone can provide brain-mimicking properties, while leading to stable gels. CONCLUSIONS: The modified freeze-thaw process enabled to minimize the temperature gradient within the large cryogel phantoms during the freeze-thaw cycle. The results of this study can help to fill the gaps in the scientific literature with regard to developing homogeneous phantoms for medical imaging. This work also provides a solid foundation for future studies in this field and could facilitate formulating new hydrogels to replicate the viscoelastic properties of soft tissues.