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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

Gross appearance and dimension analysis of the samples in the different groups before and after biomechanical testing.(A-D) Gross appearance of the biphasic scaffolds from side (A-B) and top (C-D) views before (A,C) and after (B,D) the mechanical tests. (E-G) Dimension analysis of the biphasic scaffolds (with 1, 2, 4 and 10 layers of collagen lamellae) and the native disc controls at different stages during the mechanical test (i.e., before and after pre-load, after the creep, and after the test). Bar graphs show: (E) disc diameter, (F) disc height, and (G) percentage of disc height recovery. Data are expressed as mean+-2SE of n = 2–4 experiments.
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pone.0131827.g003: Gross appearance and dimension analysis of the samples in the different groups before and after biomechanical testing.(A-D) Gross appearance of the biphasic scaffolds from side (A-B) and top (C-D) views before (A,C) and after (B,D) the mechanical tests. (E-G) Dimension analysis of the biphasic scaffolds (with 1, 2, 4 and 10 layers of collagen lamellae) and the native disc controls at different stages during the mechanical test (i.e., before and after pre-load, after the creep, and after the test). Bar graphs show: (E) disc diameter, (F) disc height, and (G) percentage of disc height recovery. Data are expressed as mean+-2SE of n = 2–4 experiments.

Mentions: The biphasic IVD scaffolds are cylindrical in shape before they undergo the pre-load steo before mechanical testing and they are disc-shaped after the tests (Fig 3A–3D). The pink color of the scaffolds corresponds to the presence of the photosensitizer, rose Bengal. Fig 3E shows the changes in diameter of the various sample groups. Two-way ANOVA indicated that there was a significant change in the diameter for each group, before pre-load and after the mechanical test (at p<0.001) and among all the groups, including the scaffolds of different layers and the native discs (at p<0.001). In addition, Bonferroni’s post-hoc tests demonstrated that the native discs exhibited significant differences when compared with the biphasic scaffolds containing 1, 2 and 4 AF-like layers (at p< = 0.001) but not with scaffolds comprised of 10 layers (p = 0.149). Furthermore, the diameter of the biphasic scaffolds significantly and linearly increased as the number of layers increased, both before pre-load (p<0.001, R2 = 0.856) and after the mechanical tests (p<0.001, R2 = 0.862). Fig 3F shows the changes in height of the disc samples. Two-way ANOVA showed that there was significant change in height among the different stages during the mechanical test (at p<0.001) and among all groups including the scaffolds with the various numbers of layers and the native discs (p = 0.045), although the latter was really marginal. Dunnett’s test showed that the disc height appeared to be significantly different before and after the pre-load as well as the creep test (p<0.001) but when we allowed for recovery, the height of the disc was not actually significantly different (p = 0.123), suggesting that it was restored. Dunnett’s test also showed that, when compared with the native discs, all the biphasic scaffolds with the different AF layers showed no significant difference in disc heights (p< = 0.267). Fig 3G shows the mean percentage disc height recovery after the mechanical test. All the biphasic scaffolds independent of the number of AF layers used, recovered to somewhere in the range of 82 to 89% of the original disc height after pre-load, while the native discs showed 99% recovery. Although the practical difference in the percentage recovery of the disc height between the biphasic scaffolds and the native disc was only ~10%, one-way ANOVA still showed statistically significant differences among groups (at p<0.001), and the difference between the native disc and all the biphasic scaffolds was significant (at p< = 0.003), independent on how many AF layers there were.


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

Choy AT, Chan BP - PLoS ONE (2015)

Gross appearance and dimension analysis of the samples in the different groups before and after biomechanical testing.(A-D) Gross appearance of the biphasic scaffolds from side (A-B) and top (C-D) views before (A,C) and after (B,D) the mechanical tests. (E-G) Dimension analysis of the biphasic scaffolds (with 1, 2, 4 and 10 layers of collagen lamellae) and the native disc controls at different stages during the mechanical test (i.e., before and after pre-load, after the creep, and after the test). Bar graphs show: (E) disc diameter, (F) disc height, and (G) percentage of disc height recovery. Data are expressed as mean+-2SE of n = 2–4 experiments.
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Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4482706&req=5

pone.0131827.g003: Gross appearance and dimension analysis of the samples in the different groups before and after biomechanical testing.(A-D) Gross appearance of the biphasic scaffolds from side (A-B) and top (C-D) views before (A,C) and after (B,D) the mechanical tests. (E-G) Dimension analysis of the biphasic scaffolds (with 1, 2, 4 and 10 layers of collagen lamellae) and the native disc controls at different stages during the mechanical test (i.e., before and after pre-load, after the creep, and after the test). Bar graphs show: (E) disc diameter, (F) disc height, and (G) percentage of disc height recovery. Data are expressed as mean+-2SE of n = 2–4 experiments.
Mentions: The biphasic IVD scaffolds are cylindrical in shape before they undergo the pre-load steo before mechanical testing and they are disc-shaped after the tests (Fig 3A–3D). The pink color of the scaffolds corresponds to the presence of the photosensitizer, rose Bengal. Fig 3E shows the changes in diameter of the various sample groups. Two-way ANOVA indicated that there was a significant change in the diameter for each group, before pre-load and after the mechanical test (at p<0.001) and among all the groups, including the scaffolds of different layers and the native discs (at p<0.001). In addition, Bonferroni’s post-hoc tests demonstrated that the native discs exhibited significant differences when compared with the biphasic scaffolds containing 1, 2 and 4 AF-like layers (at p< = 0.001) but not with scaffolds comprised of 10 layers (p = 0.149). Furthermore, the diameter of the biphasic scaffolds significantly and linearly increased as the number of layers increased, both before pre-load (p<0.001, R2 = 0.856) and after the mechanical tests (p<0.001, R2 = 0.862). Fig 3F shows the changes in height of the disc samples. Two-way ANOVA showed that there was significant change in height among the different stages during the mechanical test (at p<0.001) and among all groups including the scaffolds with the various numbers of layers and the native discs (p = 0.045), although the latter was really marginal. Dunnett’s test showed that the disc height appeared to be significantly different before and after the pre-load as well as the creep test (p<0.001) but when we allowed for recovery, the height of the disc was not actually significantly different (p = 0.123), suggesting that it was restored. Dunnett’s test also showed that, when compared with the native discs, all the biphasic scaffolds with the different AF layers showed no significant difference in disc heights (p< = 0.267). Fig 3G shows the mean percentage disc height recovery after the mechanical test. All the biphasic scaffolds independent of the number of AF layers used, recovered to somewhere in the range of 82 to 89% of the original disc height after pre-load, while the native discs showed 99% recovery. Although the practical difference in the percentage recovery of the disc height between the biphasic scaffolds and the native disc was only ~10%, one-way ANOVA still showed statistically significant differences among groups (at p<0.001), and the difference between the native disc and all the biphasic scaffolds was significant (at p< = 0.003), independent on how many AF layers there were.

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