Abstract
The use of porous 3D scaffolds for the repair of bone nonunion and osteoporotic bone is currently an area of great interest. Using a combination of thermally-induced phase separation (TIPS) and 3D-plotting (3DP), we have generated hierarchical 3DP/TIPS scaffolds made of poly(lactic-co-glycolic acid) (PLGA) and nanohydroxyapatite (nHA). A full factorial design of experiments was conducted, in which the PLGA and nHA compositions were varied between 6‒12% w/v and 10‒40% w/w, respectively, totaling 16 scaffold formulations with an overall porosity ranging between 87%‒93%. These formulations included an optimal scaffold design identified in our previous study. The internal structures of the scaffolds were examined using scanning electron microscopy and microcomputed tomography. Our optimal scaffold was seeded with MC3T3-E1 murine preosteoblastic cells and subjected to cell culture inside a tissue culture dish and a perfusion bioreactor. The results were compared to those of a commercial CellCeram™ scaffold with a composition of 40% β-tricalcium phosphate and 60% hydroxyapatite (β-TCP/HA). Media flow within the macrochannels of 3DP/TIPS scaffolds was modeled in COMSOL software in order to fine tune the wall shear stress. CyQUANT DNA assay was performed to assess cell proliferation. The normalized number of cells for the optimal scaffold was more than twofold that of CellCeram™ scaffold after two weeks of culture inside the bioreactor. Despite the substantial variability in the results, the observed improvement in cell proliferation upon culture inside the perfusion bioreactor (vs. static culture) demonstrated the role of macrochannels in making the 3DP/TIPS scaffolds a promising candidate for scaffold-based tissue engineering.
Highlights
Age is one of the primary determinants of osteoporosis
The significant improvement in cell proliferation upon culture inside the perfusion bioreactor demonstrates the role of microchannels in making these 3DP/thermally-induced phase separation (TIPS) scaffolds a promising candidate for scaffold-based tissue engineering
This paper reports differences in porosity and density based on varying the percentage of polymer and ceramic components in poly(lactic-co-glycolic acid) (PLGA)/nHA scaffolds
Summary
Age is one of the primary determinants of osteoporosis. In the United States, over 30% of individuals 80 or older have osteoporosis, and osteoporosis is the primary cause of spine and hip fracture within this age group [1]. Postmenopausal women are susceptible to osteoporosis, with women over 80 years accounting for 30% of fragility fractures and 60% of all hip fractures [1]. Bone nonunion may be treated with bone autograft, allograft, or site stimulation if non-operative techniques are unsuccessful [4]. All these treatment modalities have risks and may have fairly high rates of failure depending on the microenvironment surrounding the fracture [3]
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