The mechanics of PLGA nanofiber scaffolds with biomimetic gradients in mineral for tendon-to-bone repair

Abstract

Attachment of dissimilar materials is prone to failure due to stress concentrations that can arise at interfaces. A compositionally or structurally graded transition can dissipate these stress concentrations and thereby toughen an attachment. The interface between compliant tendon and stiff bone utilizes a monotonic change in hydroxylapatite mineral (“mineral”) content to produce a gradient in mechanical properties and mitigate stress concentrations. Previous efforts to mimic the natural tendon-to-bone attachment have included electrospun nanofibrous polymer scaffolds with gradients in mineral. Mineralization of the nanofiber scaffolds has typically been achieved using simulated body fluid (SBF). Depending on the specific formulation of SBF, mineral morphologies ranged from densely packed small crystals to platelike crystal florets. Although this mineralization of scaffolds produced increases in modulus, the peak modulus achieved remained significantly below that of bone. Missing from these prior empirical approaches was insight into the effect of mineral morphology on scaffold mechanics and on the potential for the approach to ultimately achieve moduli approaching that of bone. Here, we applied two mineralization methods to generate scaffolds with spatial gradations in mineral content, and developed methods to quantify the stiffening effects and evaluate them in the context of theoretical bounds. We asked whether either of the mineralization methods we developed holds potential to achieve adequate stiffening of the scaffold, and tested the hypothesis that the smoother, denser mineral coating could attain more potent stiffening effects. Testing this hypothesis required development of and comparison to homogenization bounds, and development of techniques to estimate mineral volume fractions and spatial gradations in modulus. For both mineralization strategies, energy dispersive x-ray analysis demonstrated the formation of linear gradients in mineral concentration along the length of the scaffolds, and Raman spectroscopic analysis revealed that the mineral produced was hydroxylapatite. Mechanical testing showed that the stiffness gradient using the new method was significantly steeper. By analyzing the scaffolds using micromechanical modeling techniques and extrapolating from our experimental results, we present evidence that the new mineralization protocol has the potential to achieve levels of stiffness adequate to contribute to enhanced repair of tendon-to-bone attachments.

Stochastic Interdigitation as a Toughening Mechanism at the Interface between Tendon and Bone

“…A number of complexities of the tendon-to-bone attachment were not included in the model, most notably a gradient in mineral and in collagen fiber orientation (9,10). Although this gradient constitutes a central focus of many tissue engineering efforts (compare to Lipner et al (45)), its origin is unclear. An ongoing uncertainty in the literature is whether the gradient in mineralization arises from interdigitating, fully mineralized features, or from a spatial gradient in mineral accumulation (9).…”

The concentration of stress at the rotator cuff tendon-to-bone attachment site is conserved across species

“…These results have ramifications for the broad sets of literature on tendon-to-bone healing, development, and tissue engineering (Lu and Thomopoulos, 2013; Smith et al, 2012; Kolluru et al, 2013; Lipner et al, 2014; Thomopoulos et al, 2010). Results suggest that a preferred range of target stresses is desirable within the tendon-to-bone attachment in animals across a three order of magnitude range of body mass, and motivate further study to determine whether extrapolation to humans is possible.…”

Basic Science in Rotator Cuff Tears

“…Despite the complexity of healing tissue engineering, research is focused on different approaches as biphasic [12] and triphasic scaffolds have [13] been generated with multiple cell types, electrospun nanofibrous, polymer scaffolds with gradients in mineral content, to better mimic the tendon to bone insertion site. More recently Libner J et al [14] presented a new mineralization protocol for creating a tendon to bone scaffold, attempting to provide more stiffness in the repair area using the mechanics of PLGA nanofiber scaffolds [14]. Thomopoulos et al [15] attempted to protect with primary immobilization the insertion site of RC repair to allow the expression of type III collagen, decorin and biglycan (extracellular matrix) until the insertion site reformed and then to start passive exercise.…”