Discipline: Technology and Engineering
Subcategory: Biomedical Engineering
Room: Virginia B
Guleid Awale - University of Connecticut
Co-Author(s): Kevin W.-H. Lo, University of Connecticut, CT; Cato T. Laurencin, University of Connecticut, CT
Critical-size bone defects have emerged as a growing epidemic in the United States, due to its high societal cost and the downsides of conventional treatment options such as autografts and allografts. Regenerative engineering is an innovative approach towards the formation of complex tissue and organ systems through the convergence of advanced material science, stem cell science, physics, developmental biology, and clinical translation. We have previously developed biocompatible, polymeric scaffolds composed of sintered poly(lactic-co-glycolic acid) (PLGA) microspheres as prospective bone grafting substitutes. In order to enhance the osteoconductivity of the scaffold, we propose the development of a novel, porous PLGA sintered microsphere scaffold. By enhancing the porosity of the scaffold, we hypothesize that it will allow for improved nutrient diffusion and waste removal, and as well as enhance cell infiltration and proliferation within the structure.
Porous PLAGA sintered microsphere scaffolds were fabricated using a modified solvent evaporation and heat sintering technique adopted from Qutachi et al. In order to induce the porosity of the microspheres, PBS was added to a 20% w/v solution of PLGA and homogenized at 23,000 rpm for 3 minutes to create the primary emulsion. 1 g of the obtained microspheres were placed in 10 mL of ethanolic sodium hydroxide (30% 0.25M NaOH; 70% ethanol) under agitation for 3 min to expose the porosity of the microspheres at the surface. A stainless steel mold was packed with the dried microspheres and heated at 60?C for 2h in order to obtain bonding between the adjacent microspheres. To confirm the morphology and porosity of the scaffolds, SEM imaging was performed and the micrographs were compared to the non-porous, sintered microsphere scaffold group. After the structure was confirmed, an MTS cell proliferation assay was conducted using MC3T3-E1 osteoblast-like cells seeded onto the scaffold. Statistical analysis between the untreated and treated experimental groups was accomplished using a Student?s t-test, where a p value < 0.05 indicated statistical significance. A pilot in vivo study was subsequently executed using a mouse calvarial defect model. After six weeks, the animals were euthanized, and x-ray, as well as histological analysis, was conducted to measure the level of bone formation. Our observations showed a significant increase in cellular proliferation and in vivo bone formation of the porous compared to the non-porous scaffold, thus illustrating its prospective usage in bone regenerative engineering. Future studies will include the enhancement of the scaffold?s mechanical strength, as well as further implantation in load-bearing animal models. References: Qutachi, Omar, et al. 'Injectable and porous PLGA microspheres that form highly porous scaffolds at body temperature.' Acta biomaterialia 10.12 (2014): 5090-5098.
Funder Acknowledgement(s): The authors gratefully acknowledge the funding from the Northeast LSAMP Bridge to the Doctorate (BD) fellowship program (1400382), the Raymond and Beverly Sackler Center for Biomedical, Biological, Physical, and Engineering Sciences, NIH DP1 AR068147, and the GE Graduate Fellowship for Innovation.
Faculty Advisor: Dr. Cato Laurencin, email@example.com
Role: I conducted the majority of the experimental planning and execution, such as the scaffold fabrication, MTS, SEM, and accompanying surgical preparations.