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    Orthopedic and Rehabilitation Engineering

    Effects of Macromolecular Infiltration on the Mechanical Properties of Synthetic Cartilage

    (H-281) Effects of Macromolecular Infiltration on the Mechanical Properties of Synthetic Cartilage

    Thursday, October 12, 2023
    2:00 PM – 3:00 PM PDT
    Location: Exhibit Hall - Row H - Poster # 281

      Presenting Author(s)

    • Wenqi Di

      Undergraduate Research Assistant and Vice President of UR BMES
      University of Rochester
      Rochester, New York, United States

      • Primary Investigator(s)

    • Mark R. Buckley

      Associate Professor
      Univerisity of Rochester
      Rochester, United States

    Introduction::

    Articular cartilage (AC) is a soft connective tissue that covers the ends of long bones in joints. AC degradation is a hallmark feature of osteoarthritis (OA). Over 70% of AC is fluid1 which helps protect the tissue and resident cells by supporting external forces (“fluid load support”)2. The permeability of AC is a property that describes how easily fluid is squeezed from the tissue. When AC permeability decreases, fluid load support is reduced. Albumin is the most abundant protein in the synovial fluid that surrounds AC3. Albumin can diffuse into AC and albumin levels are increased during OA4. Surprisingly, our previous studies show that AC permeability increases when albumin (or other macromolecules of equivalent size) diffuses into AC. These findings suggest it may be possible to tune the permeability of hydrogels (used clinically as a synthetic replacement for damaged cartilage) by controlling the concentration of macromolecules within these materials. Thus, the objective of this study was to determine how the permeability of agarose hydrogels is affected by the infiltration of large macromolecules. We hypothesize that macromolecular infiltration increases hydrogel permeability.



    Materials and Methods:: Agarose hydrogels were synthesized at three concentrations: 1%, 2%, and 4%. A microwave was used to heat the mixed solution, and the warmed solution was poured into a Petri dish before cooling and solidifying. The hydrogel was incubated overnight at 37o C with 1% v/v 0.5 μm diameter fluorescent microspheres or 30 mg/mL 40 kDa dextran overnight for testing. A cylindrical hydrogel specimen 8 mm in diameter was cut from a Petri dish using a dermal biopsy punch. The specimen was subjected to an indentation test (step displacement) using a custom-designed and fabricated apparatus integrated into a uniaxial material testing system (FIG. 1). The acquired force vs. time data was fit to the function 𝐹 = 𝐹0 + 𝐹1e-𝜆t to determine the fit parameters 𝐹0, 𝐹1, and 𝜆 using MATLAB. A 3D finite element model (FEM) of the poroelastic agarose hydrogel and indentor (FIG. 2) was constructed in the FEBIO software suite. Using iterative optimization, the model was adjusted with different values of permeability and Young’s modulus (intrinsic stiffness of the solid component of the tissue) until the fit parameters (𝐹0, 𝐹1, and 𝜆) of the simulated force versus time curve matched the fit parameters of the experimental force versus time curve.

    Results, Conclusions, and Discussions::

    Results and Discussion: Contrary to our hypothesis (and distinct from native articular cartilage), infiltration of albumin-sized macromolecules and larger microspheres did not impact agarose hydrogel permeability. An analytic model to explain our prior findings posits that nanometer-sized solutes (such as albumin) preferentially diffuse into large pores of cartilage but are unable to penetrate narrow pores. The presence of these molecules increases osmotic pressure in large pores but not in narrow pores, leading to a pressure gradient that expands large pores at the expense of small pores. Since the permeability of a porous material is strongly driven by the diameter of its largest pores, this effect substantially increases tissue permeability. To explain our findings, we estimated the pore radius a of the agarose gels based on their permeability using the equation a2=(8μKaδ)/β1, where μ is the fluid viscosity, Ka is the permeability, δ is the tortuosity, and β is the porosity. We found that the pore size is approximately 0.1 μm suggesting that 40kDa dextran (hydrodynamic radius ~ 7nm) may permeate all pores while 0.5 μm microparticles may be too large to permeate even the largest pores. Thus, our results are not inconsistent with our analytic model.


    Conclusion: Although we did not observe changes in hydrogel permeability due to macromolecular infiltration, this finding may be explained by the sizes of the solutes we tested (much smaller and much larger than the average pore size of 0.1 μm). We expect that infiltration macromolecules ~0.1 μm will alter hydrogel permeability and will test this hypothesis in future work.


     




    Acknowledgements (Optional): : We thank Yingjie Wu and Dr. Alexander Kotelsky for their assistance with this project.

    References (Optional): :

     [1] Mow, 1984; [2] Basalo, 2004; [3] Bennike, 2014; [4] Gobezie, 2007