Effects of Collagen Crosslink Augmentation on Mechanism of Compressive Load Sharing in Intervertebral Discs.

Exogenous crosslinking has been shown to have potential for treating disc degeneration and back pain due to its ability to increase the strength and toughness of the annulus fibrosus, increase intervertebral joint stability, decrease intradiscal pressure, and increase fluid flow through the disc. Some results imply that crosslink augmentation may also lead to changes in the compressive load sharing properties of the disc. The objective of the present study was to evaluate directional stress distribution changes of the disc following genipin crosslinking treatment. Bovine lumbar motion segments were randomly divided into control and crosslinked groups. Annular strains were determined from simultaneous deformation measurements at various time points during compressive creep testing. Four stress components of the annulus were then calculated according to the previously measured modulus data. Immediately after the application of a 750-N compressive load, mean axial and radial compressive stresses in the crosslinked group were twofold higher than control means. Conversely, mean lamellae-aligned and circumferential tensile stresses of the crosslinked discs were 8- and threefold lower, respectively, compared to control means. After 1-h creep loading, the two compressive mean stresses in both the control and genipin-crosslinked specimens increased approximately threefold from their initial 750-N-loaded values. The two tensile mean stresses in the crosslinked group remained lower than the respective levels of the control means after creep loading. A greater proportion of annular compressive load support under compressive creep loading, with a commensurate decrease in both tensile stresses and strains, was seen in the discs following exogenous crosslink augmentation.

Exogenous Crosslinking Restores Intradiscal Pressure of Injured Porcine Intervertebral Discs: An In Vivo Examination Using Quantitative Discomanometry.

STUDY DESIGN: In vivo examination of intradiscal pressure by quantitative discomanometry (QD). OBJECTIVE: To determine whether an injectable, exogenous crosslinking could acutely restore intradiscal pressure of stab-injured discs in vivo by short-term treatment. SUMMARY OF BACKGROUND DATA: Disc biomechanical performance depends on its integrity associated with the intradiscal pressure and mechanical properties. Genipin crosslink augmentation has demonstrated the in vitro biomechanical capability to improve intervertebral joint stability and increase mechanical properties of the annulus fibrosus. METHODS: 4 lumbar discs on each of 8 swine were randomly assigned to 4 groups: intact, injured, untreated, and crosslinked. A 16G needle was stabbed into the annulus fibrosus to create the disc injury model. An injection of 0.33% genipin solution was delivered into the annulus to treat the injury. QD technique was performed to examine the intradiscal pressure for the intact and injured discs at the time of surgery, while untreated and crosslinked discs were measured 1-week postsurgery. 4 QD parameters were analyzed and compared across the 4 groups: leakage pressure and volume, and saturation pressure and volume. RESULTS: The leakage and saturation pressures of the injured group were significantly lower than those of the intact group (P = 0.004 and P = 0.01, respectively). The leakage and saturation pressures of untreated discs were statistically equivalent to the injured levels, but with a 2-times higher saturation volume. Relative to the untreated group, the leakage pressure and saturation pressure of genipin-crosslinked discs had a 617% (P = 0.008) and a 473% increase (P = 0.007), respectively. CONCLUSION: A large disc injury produced by annular puncture immediately lowered intradiscal pressure when left untreated. Genipin crosslinking can restore intradiscal pressure acutely in vivo without any obvious morbidity associated with the injection.

Results of infected total knee arthroplasty treated with arthroscopic debridement and continuous antibiotic irrigation system.

BACKGROUND: Arthroscopic debridement with continuous irrigation system was used with success in treating infective arthritis. We evaluated the effectiveness of arthroscopic debridement coupled with antibiotic continuous irrigation system in acute presentation of late infected total knee arthroplasty. MATERIALS AND METHODS: We performed a retrospective review of medical record of patients with acute presentation of late infected total knee arthroplasty who were treated by arthroscopic debridement coupled with continuous postoperative antibiotic irrigation system. RESULTS: Seventeen patients were included in our study. 15 (88%) patients preserved their total knee prosthesis at mean of followup of 27.5 months (range, 14-28 months). Two (12%) patients failed arthroscopic protocol and finally needed two stages revision. Our study showed an 88% prosthesis retention rate in patients with acute presentation of late prosthetic knee infection. No complication was associated with use of antibiotic irrigation system. CONCLUSION: Arthroscopic debridement combined with continuous antibiotic irrigation and suction is an effective treatment for patients with acute presentation of late infected total knee arthroplasty.

Risk factors for nonunion in patients with intracapsular femoral neck fractures treated with three cannulated screws placed in either a triangle or an inverted triangle configuration.

BACKGROUND: Intracapsular femoral neck fractures are associated with high rates of nonunion. We aimed to identify risk factors for nonunion in patients with both displaced and nondisplaced intracapsular femoral neck fractures treated with three 7-mm parallel cannulated screws, placed in either a triangle or an inverted triangle configuration, using failure of fixation as the primary outcome. METHODS: Clinical and radiographic data for patients with intracapsular femoral neck fractures treated with either triangle fixation (one proximal screw and two distal screws) or inverted triangle fixation (two proximal screws and one distal screw), between January 1, 2000, and July 30, 2009, were analyzed. RESULTS: A total of 202 patients, seventy-six men and 126 women with an average age (and standard deviation) of 64.53 ± 15.81 years (range, nineteen to ninety-three years), were included in the analysis. Union occurred in 158 patients, and nonunion occurred in forty-four. There were no differences between the union and nonunion groups with respect to age, sex, fracture side, fracture angle, fracture level, or estimated bone density. There were significant differences in fracture type, fixation configuration, reduction quality, and screw-tip subchondral purchase between patients with and without union. The estimated odds ratio for fracture nonunion was 2.93 (95% confidence interval [CI], 1.08, 7.96) in subjects with displaced fractures compared with those without displaced fractures (p = 0.035), 18.92 (95% CI, 1.91, 187.09) in subjects with borderline and unacceptable reduction compared with those with anatomic reduction (p = 0.012), and 2.92 (95% CI, 1.27, 6.69) for internal fixation with a triangle configuration compared with fixation with an inverted triangle configuration (p = 0.010). CONCLUSIONS: Screw fixation with a triangle configuration, a displaced fracture, and poor reduction are risk factors for nonunion in intracapsular femoral neck fractures treated with fixation with multiple screws.

Exogenous collagen crosslinking of the intervertebral disc restores joint stability after lumbar posterior decompression surgery.

STUDY DESIGN: In vitro evaluation of a chemical, injectable intervention for discectomy induced destabilization. OBJECTIVE: To investigate the ability of two collagen crosslinking agents to restore mechanical properties to lumbar joints destabilized by surgical decompression procedures. SUMMARY OF BACKGROUND DATA: Posterior decompression surgery is a common procedure indicated for tissue pathology that interferes with surrounding neural structures. Previous in vitro, analytical, and clinical studies have shown that removal of load-supporting tissue can compromise joint stability mandating some form of postsurgical stabilization. Currently, no nonsurgical treatments are capable of restoring stability and preventing subsequent degeneration. Exogenous crosslinking of intact discs has shown a fourfold increase in joint stability. METHODS: Fifteen bovine lumbar intervertebral joints were randomly separated into methylglyoxal or genipin treatment groups. Flexion-extension flexibility was quantified in three conditions: intact, postdecompression surgery, and after crosslinking reagent injections. Instability was quantified by calculating neutral zone (NZ), percentage of hysteresis, range of motion, and percentage of strain energy. RESULTS: Simulated surgical decompression increased NZ 111% (P = 0.009), 28% (P = 0.004), range of motion 57% (P = 0.003), and decreased strain energy 37% (P = 0.004). For those discs undergoing methylglyoxal treatment NZ was subsequently reduced 68% (P = 0.012), hysteresis 28% (P = 0.018), range of motion 29% (P = 0.012), and strain energy was increased 71% (P = 0.018). For discs subjected to genipin treatment, NZ was reduced 52% (P = 0.018), hysteresis 23% (P = 0.012), range of motion 44% (P = 0.017), and strain energy was increased 66% (P = 0.012). Mean NZ was lower than intact mean after both methylglyoxal and genipin treatments, 10% and 17% less, respectively, but these differences were not significant. Mean values for all other parameters posttreatment were within 6% of the corresponding intact mean values. CONCLUSION: Injections of crosslinking reagents into lumbar intervertebral discs after simulated decompression surgery restored joint stability according to all parameters. Similar results were found for genipin and methylglyoxal reagents. Implementing exogenous collagen crosslinking as an adjunct to current surgical decompression procedures may be beneficial in preventing or delaying subsequent spinal instability and degeneration.

The effects of exogenous crosslinking on hydration and fluid flow in the intervertebral disc subjected to compressive creep loading and unloading.

STUDY DESIGN: In vitro study of genipin crosslinking effect on disc water content changes under compressive loading and unloading. OBJECTIVE: To investigate the influence of collagen crosslinking on hydration and fluid flow in different regions of intact discs, and to evaluate the nutritional implications. SUMMARY OF BACKGROUND DATA: Age-related reductions of nutrient supply and waste product removal are critically important factors in disc pathogenesis. Diffusion and fluid flow are blocked by subchondral bone thickening, cartilaginous endplate calcification, loss of hydrophilic proteoglycans, and clogging of anular pores by degraded matrix molecules. Previous studies demonstrated increased hydraulic permeability and macromolecular transport through crosslinked collagenous matrices. Genipin has also demonstrated the capability to increase retention of proteoglycans. METHODS: A total of 57 bovine lumbar motion segments were divided randomly into phosphate buffered saline and 0.33% genipin-soaked treatment groups. Water content changes were measured using a mass-loss technique in 3 intervertebral disc regions following successive stages of compressive loading and unloading (post-treatment, after 1 hour 750 N compression, and after a subsequent 24-hour period of nominal loading). Net flow of fluid into or out of a region was determined from the percentage change in mean water content from successive groups. RESULTS: Fluid flow to and from the nucleus doubled with genipin crosslinking. Relative to the buffer-only controls, overall net fluid flow increased 103% in the nucleus pulposus, 36% in the inner anulus, and was 31% less in the outer anulus of genipin treated discs. CONCLUSION: The effects of genipin crosslinking on matrix permeability and proteoglycan retention can alter hydration levels and fluid flow in the intervertebral disc. Resulting increases in fluid flow, including a doubling of flow to and from the nucleus, could lead to enhanced nutritional inflow and waste product outflow for the disc, and may have implications for emerging cell-based therapies.

The influence of exogenous cross-linking and compressive creep loading on intradiscal pressure.

This study involves a biomechanical evaluation of a prospective injectable treatment for degenerative discs. The high osmolarity of the non-degenerated nucleus pulposus attracts water contributing to the hydrostatic behavior of the tissue. This intradiscal pressure is known to drop as fluid is exuded from the matrix due to compressive loading. The objective of this study was to compare the changes in intradiscal pressure in control and genipin cross-linked intervertebral discs. Thirty bovine lumbar motion segments were randomly divided into a phosphate-buffered saline control group and a 0.33% genipin group and soaked at room temperature for 2 days. A needle pressure sensor was held in the center of the disc while short-term and static creep compressive loads were applied. The control group demonstrated a 25% higher average intradiscal pressure compared to genipin-treated discs under 750 N compressive load (p=0.029). Depressurization during static compressive creep was 56% higher in the control than in the genipin group (p=0.014). These results suggest cross-linking induced changes in the poroelastic properties of the involved tissues affected the mechanics of compressive load support in the disc with lower levels of nucleus pressure, a corresponding decrease in the elastic expansion of the annulus, and an increased axial compressive loading of the inner and outer annulus tissues. It is possible that concurrent changes in hydraulic permeability and proteoglycan retention known to be associated with genipin cross-linking were also contributors to poroelastic changes. Reduction of peak pressures and moderation of pressure fluctuations could be beneficial relative to discogenic pain.

Exogenous crosslinking recovers the functional integrity of intervertebral disc secondary to a stab injury.

Exogenous crosslinking was proved to improve the fatigue resistance of anulus fibrosus and the stability of motion segment. The effect of crosslinking on the recovery of stab-injured discs, however, was less studied. The purpose of this study is to find if the exogenous crosslinking can increase the mechanical function of injured discs. Fresh healthy porcine discs (T2/T9) from 6-month-old swine were obtained immediately following death. Anular puncture using 16 and 18 G spinal needle were used to create medium and large disc stab injury models. Three treatments were designed for each injury model. The first one is the injured discs without treatment. The second one is the injured discs soaked with phosphate buffered solution for 2 days. The third one is the injured discs soaked with 0.33% genipin solution for 2 days. The disc integrity was evaluated using quantitative discomanometry (QD) apparatus. Four QD parameters, that is, the leakage pressure and volume, and the saturate pressure and volume, were analyzed to find the efficacy of treatment. We found that soaking of genipin solution recovered the disc leakage pressure from 1.3 to 1.8 MPa in 16 G-injury-model and from 2.3 to 3.2 MPa in 18 G-injury-model, and recovered the saturate pressure from 1.6 to 2.0 MPa in 16 G-injury-model and from 2.7 to 3.7 MPa in 18 G-injury-model. The improvement of disc integrity by soaking with genipin solution indicate that the exogenous crosslinking may help the biomechanical performance of an injured disc.

Effects of exogenous crosslinking on in vitro tensile and compressive moduli of lumbar intervertebral discs.

BACKGROUND: Collagen crosslinks may play a vital role in preventing ongoing disc degeneration. Age-accumulating crosslinks have been thought to increase brittleness and reduce fatigue resistance. However recent studies have demonstrated increases in fatigue resistance, joint stability and nutritional flow properties resulting from crosslink augmentation. In this study, multi-directional moduli of bovine lumbar intervertebral discs were measured in vitro, including circumferential tension, radial compression, axial tension, and axial compression in control and crosslinked specimens. METHODS: Four types of annulus fibrosus specimens were dissected from control and crosslinked discs. Cross-sectional areas were measured using a non-contact laser measurement system and then four separate mechanical tests were conducted using a materials testing machine with custom-made loading fixtures. FINDINGS: The circumferential specimens demonstrated the highest moduli in both low stiffness and linear elastic regions. After a crosslink treatment, the modulus increased more in circumferential tension compared to axial tension and more in axial compression compared to radial compression. Other tensile properties had higher increases in circumferential tension compared to axial tension after crosslinking. INTERPRETATION: Assuming form follows function, circumferential tension is the predominant type of stress experienced by non-degenerated annulus fibrosus. The anisotropic mechanical properties of the annulus fibrosus is non-uniformly affected by crosslink augmentation. Dominant effects were in the directions with greater inherent stiffnesses. These results suggest some beneficial effects of crosslink augmentation on the mechanical properties of the annulus fibrosus: increase in ultimate strength, yield strength, toughness, and modulus in the principal stress directions.

Exogenous cross-linking increases the stability of spinal motion segments.

STUDY DESIGN: The mechanical stability of cross-linked and control spinal motion segments was evaluated using neutral zone, range of motion (ROM), and instability score metrics. OBJECTIVE: To determine if exogenous cross-linking could increase the stability of spinal motion segments. SUMMARY OF BACKGROUND DATA: The microstructure of the anulus fibrosus extracellular matrix can affect the stability of the intervertebral joint. Parallel testing in our laboratory has shown that exogenous cross-linking can improve the fatigue resistance of anulus fibrosus. METHODS: There were 3 separate experimental protocols conducted. The first study used calf lumbar intervertebral joints randomly divided into a genipin cross-linked group and phosphate buffered saline-soaked controls. After 2 days of soaking, flexion-extension ramp cycles were applied to the specimens. The second study repeated the test protocol using 22 moderately and severely degenerated human lumbar intervertebral joints. The third experiment compared the effect of cross-linking treatment on human discs with known degrees of preexisting mechanical instability. Each data set was used to assess joint instability by 3 calculations: ROM, neutral zone, and an instability score. Joint instability for each data set was evaluated using 3 calculations: ROM, neutral zone, and a novel instability score. RESULTS: These results show that cross-link augmentation can effectively reduce instability of intervertebral discs. The stabilizing effect was observed to be higher in the more mechanically unstable discs. However, cross-linking did not appear to affect the total range of sagittal motion. CONCLUSIONS: By reducing the neutral zone, exogenous cross-linking may help combat the progression of instability in degenerative disc disease.