Abstract

We investigated the kinetics of hydrochloric acid demineralization of human cortical bone with the objective of developing a method of controlled demineralization for structural bone allografts. It is known that the demineralization of cortical bone is a diffusion rate limited process with a sharp advancing reaction front. The demineralization kinetics of human cortical bone, described as the advance of the reaction front versus immersion time, were determined by measuring extraction of bone mineral in both planar and cylindrical geometries. Mathematical models based on diffusional mass transfer were developed to predict this process. The experimental data fit well with the behavior predicted by the model. The model for planar geometry is applicable to controlled demineralization of cortical bone allografts of irregular shapes such as cortical struts. The model for cylindrical geometry is appropriate when curved surfaces are involved such as in diaphyseal bone allografts. This method of demineralization has direct application to clinical modification of cortical bone allografts to potentially enhance their osteoinductive properties.

Highlights

  • Corticalbone allografts are frequentlyused in orthopedic surgery to reconstruct extensive skeletal defects encountered in the treatment of bone tumors and osteolysis in failed joint replacement^.'-^ frequently successful, incorporation of these types of grafts is slow and unpredictable, resulting in nonunion and fatigue fractures.2-6We studied the demineralization of cortical bone in an attempt to provide a method which would improve the incorporation of these types of bone grafts.The osteoinductivepotential of demineralized cortical bone has been demonstrated in numerous experimental and clinical s t ~ d i e s .T~h-e~o~steoinductive effect of demineralized cortical bone relies on matrix factors such as the bone morphogenetic proteins (BMPs)of the TGF-beta gene family and other noncollagenous proteins

  • The penetration depth of the demineralization process was obtained from the measured weight loss. This was done by normalizing the weight loss for a particular immersion time to the weight loss corresponding to total demineralization,and setting that equal to volume of the demineralized region normalized to the initial volume

  • This study shows that hydrochloric acid demineralization of human cortical bone can be described with the theory of the shrinking core used for diffusionlimited processes in fluid-solid systems.25The shrinkage of the inner unreacted core is a function of the immersiontime in acid.Corticalbone demineralization results in a sharp advancing reaction front that sepa

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Summary

Introduction

The osteoinductivepotential of demineralized cortical bone has been demonstrated in numerous experimental and clinical s t ~ d i e s .T~h-e~o~steoinductive effect of demineralized cortical bone relies on matrix factors such as the bone morphogenetic proteins (BMPs)of the TGF-beta gene family and other noncollagenous proteins. These growth factors appear to stimulate the transformation of non-osseous connective tissue cells into osteogenicand chondrogeniccells, regulate the resorption of cortical bone, and lead to formation of new b ~ n e . A variety of strong and weak acids, as well as acidic buffers, have been used for rapid decalcification.20In the case of acid demineralization using HCl, the major inorganic constituents in bone including hydroxyapatite, tricalcium phosphate, and calcium carbonate react to form calcium chloride.[21,22] A number of authors have approached the problem of understanding the process of demineralization or decalcifi~ation.I~n~p-a~r~ticular, Makarewicz et a1.121,22 whose interestin bone demineralizationstemmedfrom its importance in the production of photographic gelatin, have demonstrated that the kinetics of demineralization were limited by the rate of diffusion of acid

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