Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition
Poor nutrient transport through the cartilage endplate (CEP) is a key factor in the etiology of intervertebral disc degeneration and may hinder the efficacy of biologic strategies for disc regeneration. Yet, there are currently no treatments for improving nutrient transport through the CEP. In this...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-02-01
|
| Series: | Frontiers in Bioengineering and Biotechnology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1111356/full |
| _version_ | 1797894236986671104 |
|---|---|
| author | Mohamed Habib Mohamed Habib Shayan Hussien Oju Jeon Jeffrey C. Lotz Peter I-Kung Wu Eben Alsberg Aaron J. Fields |
| author_facet | Mohamed Habib Mohamed Habib Shayan Hussien Oju Jeon Jeffrey C. Lotz Peter I-Kung Wu Eben Alsberg Aaron J. Fields |
| author_sort | Mohamed Habib |
| collection | DOAJ |
| description | Poor nutrient transport through the cartilage endplate (CEP) is a key factor in the etiology of intervertebral disc degeneration and may hinder the efficacy of biologic strategies for disc regeneration. Yet, there are currently no treatments for improving nutrient transport through the CEP. In this study we tested whether intradiscal delivery of a matrix-modifying enzyme to the CEP improves solute transport into whole human and bovine discs. Ten human lumbar motion segments harvested from five fresh cadaveric spines (38–66 years old) and nine bovine coccygeal motion segments harvested from three adult steers were treated intradiscally either with collagenase enzyme or control buffer that was loaded in alginate carrier. Motion segments were then incubated for 18 h at 37 °C, the bony endplates removed, and the isolated discs were compressed under static (0.2 MPa) and cyclic (0.4–0.8 MPa, 0.2 Hz) loads while submerged in fluorescein tracer solution (376 Da; 0.1 mg/ml). Fluorescein concentrations from site-matched nucleus pulposus (NP) samples were compared between discs. CEP samples from each disc were digested and assayed for sulfated glycosaminoglycan (sGAG) and collagen contents. Results showed that enzymatic treatment of the CEP dramatically enhanced small solute transport into the disc. Discs with enzyme-treated CEPs had up to 10.8-fold (human) and 14.0-fold (bovine) higher fluorescein concentration in the NP compared to site-matched locations in discs with buffer-treated CEPs (p < 0.0001). Increases in solute transport were consistent with the effects of enzymatic treatment on CEP composition, which included reductions in sGAG content of 33.5% (human) and 40% (bovine). Whole disc biomechanical behavior—namely, creep strain and disc modulus—was similar between discs with enzyme- and buffer-treated CEPs. Taken together, these findings demonstrate the potential for matrix modification of the CEP to improve the transport of small solutes into whole intact discs. |
| first_indexed | 2024-04-10T07:06:53Z |
| format | Article |
| id | doaj.art-111c24307dc7416b92dc1a817bd4bd48 |
| institution | Directory Open Access Journal |
| issn | 2296-4185 |
| language | English |
| last_indexed | 2024-04-10T07:06:53Z |
| publishDate | 2023-02-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Bioengineering and Biotechnology |
| spelling | doaj.art-111c24307dc7416b92dc1a817bd4bd482023-02-27T06:31:20ZengFrontiers Media S.A.Frontiers in Bioengineering and Biotechnology2296-41852023-02-011110.3389/fbioe.2023.11113561111356Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutritionMohamed Habib0Mohamed Habib1Shayan Hussien2Oju Jeon3Jeffrey C. Lotz4Peter I-Kung Wu5Eben Alsberg6Aaron J. Fields7Department of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Mechanical Engineering, Al Azhar University, Cairo, EgyptDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Biomedical Engineering, University of Illinois, Chicago, IL, United StatesDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA, United StatesDepartment of Biomedical Engineering, University of Illinois, Chicago, IL, United StatesDepartment of Orthopaedic Surgery, University of California, San Francisco, San Francisco, CA, United StatesPoor nutrient transport through the cartilage endplate (CEP) is a key factor in the etiology of intervertebral disc degeneration and may hinder the efficacy of biologic strategies for disc regeneration. Yet, there are currently no treatments for improving nutrient transport through the CEP. In this study we tested whether intradiscal delivery of a matrix-modifying enzyme to the CEP improves solute transport into whole human and bovine discs. Ten human lumbar motion segments harvested from five fresh cadaveric spines (38–66 years old) and nine bovine coccygeal motion segments harvested from three adult steers were treated intradiscally either with collagenase enzyme or control buffer that was loaded in alginate carrier. Motion segments were then incubated for 18 h at 37 °C, the bony endplates removed, and the isolated discs were compressed under static (0.2 MPa) and cyclic (0.4–0.8 MPa, 0.2 Hz) loads while submerged in fluorescein tracer solution (376 Da; 0.1 mg/ml). Fluorescein concentrations from site-matched nucleus pulposus (NP) samples were compared between discs. CEP samples from each disc were digested and assayed for sulfated glycosaminoglycan (sGAG) and collagen contents. Results showed that enzymatic treatment of the CEP dramatically enhanced small solute transport into the disc. Discs with enzyme-treated CEPs had up to 10.8-fold (human) and 14.0-fold (bovine) higher fluorescein concentration in the NP compared to site-matched locations in discs with buffer-treated CEPs (p < 0.0001). Increases in solute transport were consistent with the effects of enzymatic treatment on CEP composition, which included reductions in sGAG content of 33.5% (human) and 40% (bovine). Whole disc biomechanical behavior—namely, creep strain and disc modulus—was similar between discs with enzyme- and buffer-treated CEPs. Taken together, these findings demonstrate the potential for matrix modification of the CEP to improve the transport of small solutes into whole intact discs.https://www.frontiersin.org/articles/10.3389/fbioe.2023.1111356/fullcartilage endplateintervertebral disc degenerationbiotransportspine biomechanicslow back paintissue engineering |
| spellingShingle | Mohamed Habib Mohamed Habib Shayan Hussien Oju Jeon Jeffrey C. Lotz Peter I-Kung Wu Eben Alsberg Aaron J. Fields Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition Frontiers in Bioengineering and Biotechnology cartilage endplate intervertebral disc degeneration biotransport spine biomechanics low back pain tissue engineering |
| title | Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition |
| title_full | Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition |
| title_fullStr | Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition |
| title_full_unstemmed | Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition |
| title_short | Intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition |
| title_sort | intradiscal treatment of the cartilage endplate for improving solute transport and disc nutrition |
| topic | cartilage endplate intervertebral disc degeneration biotransport spine biomechanics low back pain tissue engineering |
| url | https://www.frontiersin.org/articles/10.3389/fbioe.2023.1111356/full |
| work_keys_str_mv | AT mohamedhabib intradiscaltreatmentofthecartilageendplateforimprovingsolutetransportanddiscnutrition AT mohamedhabib intradiscaltreatmentofthecartilageendplateforimprovingsolutetransportanddiscnutrition AT shayanhussien intradiscaltreatmentofthecartilageendplateforimprovingsolutetransportanddiscnutrition AT ojujeon intradiscaltreatmentofthecartilageendplateforimprovingsolutetransportanddiscnutrition AT jeffreyclotz intradiscaltreatmentofthecartilageendplateforimprovingsolutetransportanddiscnutrition AT peterikungwu intradiscaltreatmentofthecartilageendplateforimprovingsolutetransportanddiscnutrition AT ebenalsberg intradiscaltreatmentofthecartilageendplateforimprovingsolutetransportanddiscnutrition AT aaronjfields intradiscaltreatmentofthecartilageendplateforimprovingsolutetransportanddiscnutrition |