Compressive Mechanical Properties of Diabetic and Non-Diabetic Plantar Soft Tissue - Center for Limb Loss and MoBility
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Compressive Mechanical Properties of Diabetic and Non-Diabetic Plantar Soft Tissue

Introduction

A severe and costly complication of diabetes is plantar ulceration, which can often lead to amputation of the affected limb. Approximately 24 million Americans were estimated to have diabetes in 2007.1 In 2004, about 71,000 nontraumatic lower-limb amputations were performed in people with diabetes, accounting for more than 60% of all nontraumatic lower limb amputations.1 It is estimated that 15% of diabetic individuals will develop a foot ulcer during their lifetime2 and 23% may develop a foot ulcer annually.3 Given that ulcer-related costs averaged $13,179 per episode in 2001,4 it can be seen that a large portion of the costs associated with all diabetes-related chronic complications, reported as $58 billion in 2007,5 may be attributed to ulceration. There is clearly a need to further develop preventative measures as well as improve treatment options to reduce the costs and morbidity associated with ulcer incidence. These developments require a better understanding of the causes of ulcer formation.

Plantar ulceration may result from a combination of factors including peripheral neuropathy resulting in insensate feet,6,7,8 increased pressures, and repetitive mechanical trauma beneath the foot,5,9 and compromised healing due to poor vascular supply.7 Among these factors, aberrant plantar pressures are routinely used as an indicator of ulcer risk10 and may result from changes in the properties of the natural cushioning fat pad beneath the foot, i.e., the plantar soft tissue11 that affect its ability to bear load and function properly. The plantar soft tissue in the healthy foot has a specialized structure consisting of fat-filled septal chambers12,13 that function to dissipate stresses by deforming,14 to maintain normal plantar pressures,15 and to absorb the impact of heel strike to an extent.16 The elastic septa in dysvascular and diabetic feet tend to be thicker and considerably fragmented as compared to non-diabetic feet.17 Continued hyperglycemia resulting in glycation of proteins is believed to be a major cause of detrimental changes in diabetic tissues such as collagen cross-links that decrease the fexibility of collagenous tissues and thereby compromise their mechanical integrity.18,19

Subsequently, several key mechanical property changes in the plantar tissue have been demonstrated to occur with diabetes. Diabetes has been shown to increase energy loss in heel pads.20,21,22 Diabetic subjects with peripheral neuropathy and a history of ulcers have been shown to have stiffer tissue23 and harder tissue24 than that of age-matched controls. Older diabetic plantar tissue has been demonstrated to be stiffer25,26 and thinner25 than young, non-diabetic tissue. However, these results are potentially confounded by age. This increased stiffness in diabetic plantar tissue has been attributed to the deeper layer of tissue.27 Diabetes has also been shown to increase shear stiffness of plantar tissue.28,24 All of these studies may be limited as they are structural in nature (i.e., of the whole intact foot vs. isolated tissue specimens and hence do not address changes that occur with diabetes to the plantar fat alone), the duration of diabetes is not always indicated, and not all regions under the foot have been examined.

Material properties of diabetic tissue would be extremely useful if applied to a computational model of the foot as they would enable rapid, comprehensive, and quantitative study to optimize orthoses and footwear without burdening patients or utilizing costly cadaveric experiments. There are few studies that have examined the material properties of the plantar soft tissue.29,30 However, these studies do not investigate diabetic tissue and are limited as they assume a frictionless specimenplaten interface without validation. Since it is difficult to obtain true material properties experimentally due to imperfect boundary conditions, inverse finite element techniques31,32 could be used to generate geometry independent properties from isolated specimens tested with controlled boundary conditions. Additionally, duration of diabetes is important to control for since tissue changes may only occur 15 years after the onset of diabetes.6 Finally, since it has been shown that plantar tissue properties vary by location28 and that certain plantar locations are more susceptible to ulceration than others,33,34 including the hallux, metatarsal heads, and calcaneus, it would be useful to examine mechanical properties at these plantar locations. Further, the lateral midfoot is also of interest since it bears load during gait.35

Thus, the purpose of this study is to characterize the mechanical properties of isolated plantar tissue specimens from both diabetic and non-diabetic feet at six relevant locations. Knowledge of these mechanical properties is critical to understanding the possible mechanisms of ulcer formation in diabetic patients and finding ways of compensating for detrimental tissue changes to prevent amputation in this high-risk population.

Originally published in Journal of Biomechanics, Vol. 43 (2010) 17541760.


Methods

Eight fresh frozen cadaveric feet (four diabetic, and four non-diabetic) were purchased from the National Disease Research Interchange. Institutional Review Board approval was obtained for this study from the Human Subjects Division at the University of Washington. Donors were of similar age and weight based on a two-sample t-test. All feet were harvested within 24 hours of post-mortem, sealed in plastic bags, and kept frozen until testing when they were defrosted overnight in a cooler. Six plantar tissue specimens were obtained from each foot at locations of interest, namely the hallux; first, third, and fifth metatarsal heads; lateral midfoot; and calcaneus (Figure 1a). The plantar soft tissue was dissected free from the underlying muscle and bone, cut into cylindrical specimens using a 1.905 cm diameter punch (Figure 1b), and further dissected from the skin by using a scalpel to maintain in vivo thickness (approximately 311 mm, depending on the location). Specimens were stored on ice until immediately prior to testing. One foot was tested per day and specimen testing order was randomized to minimize any effect due to time between dissection and testing.

Specimen locations a) at the hallux (ha); first, third, and fifth metatarsal heads (m1, m3, and m5); lateral midfoot (la); and calcaneus (ca) and b), a typical plantar tissue specimen before skin removal.

Figure 1: Specimen locations a) at the hallux (ha); first, third, and fifth metatarsal heads (m1, m3, and m5); lateral midfoot (la); and calcaneus (ca) and b), a typical plantar tissue specimen before skin removal.

Each specimen was then placed in an environmental chamber between two platens covered with 220-grit sandpaper (Figure 2). The chamber was designed to heat a water bath below the platen and create a moist environment near 100% humidity and at 35° C to approximate conditions in vivo. This set-up was attached to an ElectroForce 3200 materials testing machine. The bottom platen was raised to apply a 0.1 N compressive load and specimen initial thickness was measured. A biomechanically realistic target load was used to determine the target displacement. The target load was calculated by using a method described previously,28 which based the applied force on donor weight and the cross-sectional area of the tissue specimen along with normative ground reaction force and contact area data.36 The isolation effects from separating specimens from their surrounding tissue were also accounted for.37 In load control, the specimen underwent 10 1-Hz sine waves from 10 N to the target load; the maximal absolute displacement was noted as the target displacement. Target prescribed strain was calculated as target displacement divided by the initial thickness. The sample was allowed to recover in an unloaded state for 10 minutes after the load control test followed by a brief tuning period. Triangle wave tests consisted of 30 cycles to the prescribed strain at each of five frequencies of 1, 2, 3, 5, and 10 Hz in a randomized order. The force and displacement data were acquired at 1,000 Hz except for the 10 Hz triangle wave data that were acquired at 5,000 Hz. Peak stress (max force at the prescribed strain divided by original specimen area), peak strain (max displacement at the prescribed strain divided by initial specimen thickness), modulus (slope of the loading stressstrain curve after the infection point), and energy loss (area between the loading and unloading stressstrain curves) were recorded for each frequency and location tested.

Experimental set-up showing specimen in environmental chamber a) between sandpaper-covered platens and b) after sealing to maintain in vivo conditions of near 100% humidity and 35° C.

Figure 2: Experimental set-up showing specimen in environmental chamber a) between sandpaper-covered platens and b) after sealing to maintain in vivo conditions of near 100% humidity and 35° C.


Linear mixed effect regression was used to determine the association between soft tissue measurements (dependent variables, e.g., energy loss) and diabetes status, frequency, and location (independent variables) using R Foundation 2.9.0. The overall study design had two levels:

  • Between subject level (diabetes status)
  • Within subject level (location and frequency)

Results

Figure 3: Typical nonlinear stress–strain response with a toe region up to the inflection point followed by a rapid increase in stiffness at higher strains and showing increase in peak stress, modulus, and energy loss with increase in frequency.

Figure 3: Typical nonlinear stress–strain response with a toe region up to the inflection point followed by a rapid increase in stiffness at higher strains and showing increase in peak stress, modulus, and energy loss with increase in frequency.

The stress-strain response for all specimens was nonlinear with a large toe region up to the infection point followed by a rapid increase in stiffness at higher strains (Figure 3). Plantar soft tissue from diabetic feet had significantly higher mean modulus than soft tissue from non-diabetic feet. For the number of specimens tested, diabetic feet had similar energy loss. Diabetic feet trended towards thinner tissue than non-diabetic feet. However, these differences were not significant. Peak stress was significantly higher in diabetic feet yet peak strain was not significantly different.

The plantar soft tissue demonstrated strain rate dependence as both modulus (Figure 4a) and energy loss (Figure 5a) increased with increasing frequency. Modulus varied with frequency in an overall comparison of both diabetic and non-diabetic specimens and pair-wise differences were found between certain frequencies. Energy loss varied with frequency and all pair-wise differences were significant. Peak stress was also found to increase with frequency (Figure 6a) despite no change in peak strain with an increase in frequency (Figure 7a).

Mean modulus as a function of a) frequency across all locations and b) location across all frequencies

Figure 4: Mean modulus as a function of a) frequency across all locations and b) location across all frequencies where error bars represent standard deviations, N = non-diabetic; D = diabetic; ha = hallux; m1, m3; and m5 = first, third, and fifth metatarsals; la = lateral midfoot; and ca = calcaneus.

There were no overall differences (p = .3) for both diabetic and non-diabetic specimens between all locations tested and modulus. However, energy loss varied with location (Figure 5) with an overall significance of p = .0001. Pair-wise differences were found between certain locations. There were no pair-wise contrasts between locations tested and peak strain and peak stress that met the Bonferroni criterion (p < .0033). Interestingly, the highest peak stress for non-diabetic specimens was observed at the location of the lowest peak stress for diabetic specimens (third metatarsal, Figure 6b). An examination of the heel vs. all other locations showed that mean thickness at the heel was significantly higher. Although mean modulus and, in general, mean energy loss were lower at the heel, these findings were only borderline significant. Peak stress and peak strain did not vary between the heel and other locations.

Mean energy loss as a function of a) frequency across all locations and b) location across all frequencies

Figure 5: Mean energy loss as a function of a) frequency across all locations and b) location across all frequencies where error bars represent standard deviations, N = non-diabetic; D = diabetic; ha = hallux; m1, m3, and m5 = first, third, and fifth metatarsals; la = lateral midfoot; and ca = calcaneus.

Mean peak stress as a function of a) frequency across all locations and b) location across all frequencies

Figure 6: Mean peak stress as a function of a) frequency across all locations and b) location across all frequencies where error bars represent standard deviations, N = non-diabetic; D = diabetic; ha = hallux; m1, m3, and m5 = first, third, and fifth metatarsals; la = lateral midfoot; and ca = calcaneus.

Mean peak strain as a function of a) frequency across all locations and b) location across all frequencies

Figure 7: Mean peak strain as a function of a) frequency across all locations and b) location across all frequencies where error bars represent standard deviations, N = non-diabetic; D = diabetic; ha = hallux; m1, m3, and m5 = first, third, and fifth metatarsals; la = lateral midfoot; and ca = calcaneus.



Conclusion

This study demonstrates that changes occur in the compressive mechanical properties of the plantar soft tissue with diabetes, most notably making it stiffer and thereby compromising its ability to dissipate the stresses borne by the foot, which may increase ulceration risk. These structural results could be used to generate material properties for all areas of the plantar soft tissue in the diabetic foot with implications for foot computational modeling efforts and potentially for orthotic pressure reduction devices.

To read the full project description, please see:

Compressive Mechanical Properties of Diabetic and Non-Diabetic Plantar Soft Tissue. Pai S, Ledoux WR. J Biomech. 2010 Jun 18;43(9):1754-60. Epub 2010 Mar 6. PMID: 20207359.


Acknowledgements

This study was supported by the National Institutes of Health grant 1R01 DK75633-03 and the Department of Veterans Affairs, RR&D Service grant A4843C. The authors would also like to thank Jane Shofer, M.S. for the statistical analysis, Michael Fassbind, M.S. for equipment design, and Paul Vawter for assisting with data analysis.


Related


Research Team

Shruti Pai, M.S., Pre-Doctoral Candidate
William R. Ledoux, Ph.D.


References

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