Functionalized Nanoscaffolds to Promote Osteogenic Differentiation in Adipose Derived Human Mesenchymal Stem Cells

Venu Polineni

doi:10.23937/2469-570x/1410003

Abstract

Biocompatible polymers have been successfully implemented to generate nanofibers for bone tissue engineering. This work focused on generating and functionalizing Poly-l-Lactic-coGlycolic Acid (PLGA) nanofiber scaffolds in the range of 700 nm using the electrospinning technique. Our specific objective is to design synthetic biodegradable scaffolds comprising electrospun nanofibers that will not only be osteoconductive but also contain porosity for bone cell ingrowth enhanced with Adipose derived human Mesenchymal Stem Cells (AdhMSCs) and a sufficient amount of bioactive ingredient such as Demineralized Bone Matrix (DBM) that would serve as a more conducive framework for cell adhesion, proliferation, and differentiation. Cell-scaffolds and controls were subject to immunohistochemistry and visualized using laser scanning confocal microscopy. Osteocalcin and collagen were expressed the highest in cells grown on PLGA nanofibers but were low in cells grown on PLGA film or cells grown without PLGA. Cell viability data showed that PLGA did not cause any significant cell death, therefore mitigating biocompatibility concerns. Our results demonstrate that the nanoscaffolds support the cell proliferation and differentiation and can be used in osteogenic applications.

Highlights

Bone can spontaneously heal and restore function without significant scarring; there are several conditions where this ability is compromised, including critical-sized defects through traumatic injury, osteomyelitis, or bone tumor resections
Our specific objective is to design synthetic biodegradable scaffolds comprising electrospun nanofibers that will be osteoconductive and contain porosity for bone cell ingrowth enhanced with Adipose derived human Mesenchymal Stem Cells (AdhMSCs) and a sufficient amount of bioactive ingredient such as Demineralized Bone Matrix (DBM) that would serve as a more conducive framework for cell adhesion, proliferation, and differentiation
Osteocalcin and collagen were expressed the highest in cells grown on Poly-l-Lactic-coGlycolic Acid (PLGA) nanofibers but were low in cells grown on PLGA film or cells grown without PLGA

Summary

Introduction

Bone can spontaneously heal and restore function without significant scarring; there are several conditions where this ability is compromised, including critical-sized defects through traumatic injury, osteomyelitis, or bone tumor resections. DBM has been proven to be osteoinductive in the athymic rat model and has the most robust osteoinductive response of all the DBM product offerings fibers that is ideal for extraction sites due to its excellent osteoinductivity and osteoconductivity properties and its ability to be placed in extraction site defects [23] Such matrix displayed a significantly enhanced ability to serve as an osteoconductive graft substitute compared to the particulate form. The stem cell-based approach proposed in our work provide the advantages of both cellular and molecular therapies for bone regeneration treatments and we believe that the DBM usage would possess essential characteristics such as biocompatibility and specific physical, mechanical, chemical, and structural/architectural properties as well as would enhance functionalized scaffold building that can meet requirements for bone tissue engineering, and help in developing such scaffolds to provide a great opportunity to investigate the impact of microenvironments on the fate of stem cells. By designing biomaterials and such scaffolds that maximally enhance cell attachment, migration, proliferation, and differentiation, we will develop the value ofthese materials for improving implant fixation, fusion technology needs, and musculoskeletal tissue repair

Experimental Methods

Results and Discussion

Conclusions