title: Region and strain-dependent diffusivities of glucose and lactate in healthy human cartilage endplate.
abstract: The cartilage endplate (CEP) is implicated as the main pathway of nutrient supply to the healthy human intervertebral disc (IVD). In this study, the diffusivities of nutrient/metabolite solutes in healthy CEP were assessed, and further correlated with tissue biochemical composition and structure. The CEPs from non-degenerated human IVD were divided into four regions: central, lateral, anterior, and posterior. The diffusivities of glucose and lactate were measured with a custom diffusion cell apparatus under 0%, 10%, and 20% compressive strains. Biochemical assays were conducted to quantify the water and glycosaminoglycan (GAG) contents. The Safranin-O and Ehrlich׳s hematoxylin and eosin staining and scanning electron microscopy (SEM) were performed to reveal the tissue structure of the CEP. Average diffusivities of glucose and lactate in healthy CEP were 2.68±0.93×10-7cm2/s and 4.52±1.47×10-7cm2/s, respectively. Solute diffusivities were region-dependent (p<0.0001) with the highest values in the central region, and mechanical strains impeded solute diffusion in the CEP (p<0.0001). The solute diffusivities were significantly correlated with the tissue porosities (glucose: p<0.0001, r=0.581; lactate: p<0.0001, r=0.534). Histological and SEM studies further revealed that the collagen fibers in healthy CEP are more compacted than those in the nucleus pulposus (NP) and annulus fibrosus (AF) and show no clear orientation. Compared to human AF and NP, much smaller solute diffusivities in human CEP suggested that it acts as a gateway for solute diffusion through the disc, maintaining the balance of nutritional environment in healthy human disc under mechanical loading and preventing the progression of disc degeneration.
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, United States; Department of Orthopaedics, Medical University of South Carolina (MUSC), Charleston, SC, United States.
authors.forename: Yongren
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, United States.
authors.forename: Sarah E
authors.initials: SE
authors.lastname: Cisewski
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, United States.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Wegner
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, United States.
authors.forename: Shichang
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Orthopaedics, Medical University of South Carolina (MUSC), Charleston, SC, United States.
authors.forename: Vincent D
authors.initials: VD
authors.lastname: Pellegrini
authors.affiliation: Department of Statistics, Florida State University, Tallahassee, FL, United States.
authors.forename: Elizabeth H
authors.initials: EH
authors.lastname: Slate
authors.affiliation: Department of Bioengineering, Clemson University, Clemson, SC, United States; Department of Orthopaedics, Medical University of South Carolina (MUSC), Charleston, SC, United States. Electronic address: haiyao@clemson.edu.
authors.forename: Hai
authors.initials: H
authors.lastname: Yao
mesh_terms: D002356:Cartilage / Q000378:metabolism*; D004058:Diffusion; D005260:Female; D005947:Glucose / Q000378:metabolism*; D006025:Glycosaminoglycans / Q000378:metabolism; D006801:Humans; D007403:Intervertebral Disc / Q000378:metabolism* / Q000502:physiology; D055959:Intervertebral Disc Degeneration / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D013314:Stress, Mechanical; D014867:Water / Q000378:metabolism
chemical_list: D006025:Glycosaminoglycans; D014867:Water; D019344:Lactic Acid; D005947:Glucose
keywords: Cartilage endplate; Intervertebral disc; Mechanical strain; Nutrient transport; Solute diffusivity