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A Structurally and Functionally Biomimetic Biphasic Scaffold for Intervertebral Disc Tissue Engineering.

Choy AT, Chan BP - PLoS ONE (2015)

Bottom Line: On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc.Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery.However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs.

View Article: PubMed Central - PubMed

Affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Hong Kong Special Administrative Region, China.

ABSTRACT
Tissue engineering offers high hopes for the treatment of intervertebral disc (IVD) degeneration. Whereas scaffolds of the disc nucleus and annulus have been extensively studied, a truly biomimetic and mechanically functional biphasic scaffold using naturally occurring extracellular matrix is yet to be developed. Here, a biphasic scaffold was fabricated with collagen and glycosaminoglycans (GAGs), two of the most abundant extracellular matrix components in the IVD. Following fabrication, the scaffold was characterized and benchmarked against native disc. The biphasic scaffold was composed of a collagen-GAG co-precipitate making up the nucleus pulposus-like core, and this was encapsulated in multiple lamellae of photochemically crosslinked collagen membranes comprising the annulus fibrosus-like lamellae. On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc. The annulus-independent nature of disc height recovery suggests that the fluid replacement function of the engineered nucleus pulposus core might mimic this hitherto unique feature of native disc. Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery. However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs. This study contributes to the rationalized design and development of a biomimetic and mechanically viable biphasic scaffold for IVD tissue engineering.

No MeSH data available.


Related in: MedlinePlus

Bar charts showing the mechanical properties of samples during the creep and recovery phases of the mechanical tests.The mechanical properties of the fabricated biphasic scaffolds and native IVD (A-D) during the creep and (E-H) recovery phases. (A&E) Elastic compliance (E, mm/N); (B&F) Viscous compliance (V, mm/N); (C&G) Time constants (T, seconds) and (D&H) Stretch constants (B). Data are expressed as mean±2SE of n = 2–4 experiments.
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pone.0131827.g005: Bar charts showing the mechanical properties of samples during the creep and recovery phases of the mechanical tests.The mechanical properties of the fabricated biphasic scaffolds and native IVD (A-D) during the creep and (E-H) recovery phases. (A&E) Elastic compliance (E, mm/N); (B&F) Viscous compliance (V, mm/N); (C&G) Time constants (T, seconds) and (D&H) Stretch constants (B). Data are expressed as mean±2SE of n = 2–4 experiments.

Mentions: Fig 5A shows changes in elastic compliance (E, in mm/N) during creep. Biphasic scaffolds with 1, 2 and 4 layers of lamellae seemed to have higher compliance values than did those with 10 layers and the native disc, which have similar elastic compliance. However, one-way ANOVA indicated that the difference was marginal (p = 0.067). Nevertheless, Dunnett’s post-hoc test showed that there was significant difference between the native disc and the 4-layer scaffold groups (p = 0.040) but not with the other groups including the 10-layer group (p> = 0.281). Fig 5B shows changes in viscous compliance (V, in mm/N) during creep. One-way ANOVA showed that there was significant difference in V among the different samples (p = 0.002) while Dunnett’s T3 post-hoc test showed that the differences between the native disc and all but the 2-layer groups were statistically significant (at p< = 0.049). Fig 5C shows changes in the time constant (T, in sec) during creep. One-way ANOVA showed that there was no significant difference among any of the groups (p = 0.571). Fig 5D shows the stretch constant (B) during creep. One-way ANOVA showed that there was significant difference in B among the different groups (p = 0.001), while Bonferroni’s post-hoc test showed that native disc was significantly different from all the fabricated biphasic scaffolds (at p< = 0.031). Linear regression analyses demonstrated that there was no significant linear trend in the mechanical properties as the number of layers increased (p>0.05). Instead, the association between the compliance parameters and the number of layers in the biphasic scaffold was in general non-linear, such that the compliance parameters of 1, 2 and 4 layers were higher than the 10-layer group, which was similar to that of the native disc. Fig 5E shows the changes in elastic compliance (E) during recovery; one-way ANOVA showed that the difference in E among the different groups was insignificant (p = 0.493). Fig 5F shows the changes in viscous compliance (V) during recovery; in this case, one-way ANOVA showed that there was a significant difference in V among the different samples (p = 0.040), while Dunnett’s test showed that the difference between the native disc and the 4-layer group was statistically significant (p = 0.024). Fig 5G shows the changes in the time constant (T) during recovery; here, one-way ANOVA showed that the difference was not statistically significant (p = 0.099). Fig 5H shows changes in the stretch constant (B) during recovery; one-way ANOVA showed that the difference was statistically significant (at p<0.001) while Bonferroni’s post-hoc test indicated that native disc was significantly different from all the fabricated biphasic scaffolds (at p< = 0.001). Linear regression analyses showed that there was no significant linear trend in the mechanical properties as the number of layers increased (p>0.05). Instead, the association between the number of layers of the biphasic scaffold and the mechanical parameters was in general non-linear. Raw data on the dimension and mechanical parameters of the constructs during the mechanical tests were included as Supplementary Information.


A Structurally and Functionally Biomimetic Biphasic Scaffold for Intervertebral Disc Tissue Engineering.

Choy AT, Chan BP - PLoS ONE (2015)

Bar charts showing the mechanical properties of samples during the creep and recovery phases of the mechanical tests.The mechanical properties of the fabricated biphasic scaffolds and native IVD (A-D) during the creep and (E-H) recovery phases. (A&E) Elastic compliance (E, mm/N); (B&F) Viscous compliance (V, mm/N); (C&G) Time constants (T, seconds) and (D&H) Stretch constants (B). Data are expressed as mean±2SE of n = 2–4 experiments.
© Copyright Policy
Related In: Results  -  Collection

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Show All Figures
getmorefigures.php?uid=PMC4482706&req=5

pone.0131827.g005: Bar charts showing the mechanical properties of samples during the creep and recovery phases of the mechanical tests.The mechanical properties of the fabricated biphasic scaffolds and native IVD (A-D) during the creep and (E-H) recovery phases. (A&E) Elastic compliance (E, mm/N); (B&F) Viscous compliance (V, mm/N); (C&G) Time constants (T, seconds) and (D&H) Stretch constants (B). Data are expressed as mean±2SE of n = 2–4 experiments.
Mentions: Fig 5A shows changes in elastic compliance (E, in mm/N) during creep. Biphasic scaffolds with 1, 2 and 4 layers of lamellae seemed to have higher compliance values than did those with 10 layers and the native disc, which have similar elastic compliance. However, one-way ANOVA indicated that the difference was marginal (p = 0.067). Nevertheless, Dunnett’s post-hoc test showed that there was significant difference between the native disc and the 4-layer scaffold groups (p = 0.040) but not with the other groups including the 10-layer group (p> = 0.281). Fig 5B shows changes in viscous compliance (V, in mm/N) during creep. One-way ANOVA showed that there was significant difference in V among the different samples (p = 0.002) while Dunnett’s T3 post-hoc test showed that the differences between the native disc and all but the 2-layer groups were statistically significant (at p< = 0.049). Fig 5C shows changes in the time constant (T, in sec) during creep. One-way ANOVA showed that there was no significant difference among any of the groups (p = 0.571). Fig 5D shows the stretch constant (B) during creep. One-way ANOVA showed that there was significant difference in B among the different groups (p = 0.001), while Bonferroni’s post-hoc test showed that native disc was significantly different from all the fabricated biphasic scaffolds (at p< = 0.031). Linear regression analyses demonstrated that there was no significant linear trend in the mechanical properties as the number of layers increased (p>0.05). Instead, the association between the compliance parameters and the number of layers in the biphasic scaffold was in general non-linear, such that the compliance parameters of 1, 2 and 4 layers were higher than the 10-layer group, which was similar to that of the native disc. Fig 5E shows the changes in elastic compliance (E) during recovery; one-way ANOVA showed that the difference in E among the different groups was insignificant (p = 0.493). Fig 5F shows the changes in viscous compliance (V) during recovery; in this case, one-way ANOVA showed that there was a significant difference in V among the different samples (p = 0.040), while Dunnett’s test showed that the difference between the native disc and the 4-layer group was statistically significant (p = 0.024). Fig 5G shows the changes in the time constant (T) during recovery; here, one-way ANOVA showed that the difference was not statistically significant (p = 0.099). Fig 5H shows changes in the stretch constant (B) during recovery; one-way ANOVA showed that the difference was statistically significant (at p<0.001) while Bonferroni’s post-hoc test indicated that native disc was significantly different from all the fabricated biphasic scaffolds (at p< = 0.001). Linear regression analyses showed that there was no significant linear trend in the mechanical properties as the number of layers increased (p>0.05). Instead, the association between the number of layers of the biphasic scaffold and the mechanical parameters was in general non-linear. Raw data on the dimension and mechanical parameters of the constructs during the mechanical tests were included as Supplementary Information.

Bottom Line: On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc.Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery.However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs.

View Article: PubMed Central - PubMed

Affiliation: Tissue Engineering Laboratory, Department of Mechanical Engineering, The University of Hong Kong, Hong Kong Special Administrative Region, China.

ABSTRACT
Tissue engineering offers high hopes for the treatment of intervertebral disc (IVD) degeneration. Whereas scaffolds of the disc nucleus and annulus have been extensively studied, a truly biomimetic and mechanically functional biphasic scaffold using naturally occurring extracellular matrix is yet to be developed. Here, a biphasic scaffold was fabricated with collagen and glycosaminoglycans (GAGs), two of the most abundant extracellular matrix components in the IVD. Following fabrication, the scaffold was characterized and benchmarked against native disc. The biphasic scaffold was composed of a collagen-GAG co-precipitate making up the nucleus pulposus-like core, and this was encapsulated in multiple lamellae of photochemically crosslinked collagen membranes comprising the annulus fibrosus-like lamellae. On mechanical testing, the height of our engineered disc recovered by ~82-89% in an annulus-independent manner, when compared with the 99% recovery exhibited by native disc. The annulus-independent nature of disc height recovery suggests that the fluid replacement function of the engineered nucleus pulposus core might mimic this hitherto unique feature of native disc. Biphasic scaffolds comprised of 10 annulus fibrosus-like lamellae had the best overall mechanical performance among the various designs owing to their similarity to native disc in most aspects, including elastic compliance during creep and recovery, and viscous compliance during recovery. However, the dynamic mechanical performance (including dynamic stiffness and damping factor) of all the biphasic scaffolds was similar to that of the native discs. This study contributes to the rationalized design and development of a biomimetic and mechanically viable biphasic scaffold for IVD tissue engineering.

No MeSH data available.


Related in: MedlinePlus