Increased Internal Porosity and Surface Area of Hydroxyapatite Accelerates Healing and Compensates for Low Bone Marrow Mesenchymal Stem Cell Concentrations in Critically-Sized Bone Defects

Eileen Dawson,Melissa Samano,Matthew Murphy,Richard Suzuki

doi:10.3390/app8081366

Abstract

For clinical treatment of skeletal defects, osteoinductive scaffolds must have the ability to conform to the unique geometry of the injury site without sacrificing biologically favorable properties, including porosity. This investigation seeks to combine the osteoinductive properties of porous hydroxyapatite (HA) scaffolds with the beneficial handling characteristics of granules or putties, while evaluating the effects of mesenchymal stem cell (MSC) concentration on the composite grafts’ ability to regenerate bone in vivo. The results demonstrate that porous HA granules regenerate significantly larger volumes of bone compared to non-porous HA. Increased MSC concentrations in autologous bone marrow aspirate (BMA) contributed to greater bone regeneration. This effect was most predominant with non-porous HA. While the extent of bone regeneration using non-porous HA was strongly correlated with MSC concentration of the marrow, porous HA microparticles combined with autologous BMA were successful in faster treatment of critically-sized bone defects and with less dependence on the MSC concentration than non-porous HA.

Highlights

Critically-sized bone defects arise from traumatic injury, tumor resection, autologous bone graft harvesting, and surgical procedures, including spinal fusion
We recently reported that many Food and Drug Administration (FDA)-cleared or approved biomaterials for bone healing are not efficient at retaining bone marrow-derived cells and, in many instances, were cytotoxic, with pH values less than 7 or greater than 10 when reconstituted in plasma or saline [16]
We investigated the combination of autologous bone marrow aspirate with porous or non-porous HA granules

Summary

Introduction

Critically-sized bone defects arise from traumatic injury, tumor resection, autologous bone graft harvesting, and surgical procedures, including spinal fusion. Autografts, considered the gold standard in bone substitutes, are impractical for use in larger defects, as graft size would be limited to patient sample availability. Autografts are successful in defect treatment because they combine a number of key components necessary for tissue growth. Bone regeneration requires contributions from all aspects of the “tissue engineering paradigm”, including progenitor cells, which are a scaffold to guide tissue formation and remodeling, and biochemical/biomechanical stimuli. Significant research has investigated various biomaterials and scaffolding techniques with osteoconductive or osteoinductive properties. Among these biomaterials is hydroxyapatite (HA), Appl.

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