Thermoreversible hyaluronan-hydrogel and autologous nucleus pulposus cell delivery regenerates human intervertebral discs in an ex vivo, physiological organ culture model

Autor: L Haglund, M D'Este, Derek H. Rosenzweig, Jean Ouellet, Thomas Steffen, A P Mathieu, Michael H. Weber, David Eglin, Rayan Fairag, L Li
Jazyk: angličtina
Rok vydání: 2018
Předmět:
Male
0301 basic medicine
Pathology
T1ρ magnetic resonance imaging
lcsh:Diseases of the musculoskeletal system
Compressive Strength
Acrylic Resins
02 engineering and technology
chemistry.chemical_compound
Tissue engineering
Hyaluronic acid
Hyaluronic Acid
nucleus pulposus
Temperature
Hydrogels
Middle Aged
021001 nanoscience & nanotechnology
musculoskeletal system
Magnetic Resonance Imaging
human intervertebral disc
medicine.anatomical_structure
tissue engineering
Self-healing hydrogels
Female
Proteoglycans
autologous cell implantation
0210 nano-technology
musculoskeletal diseases
medicine.medical_specialty
lcsh:Surgery
Organ culture
Transplantation
Autologous
Collagen Type I
03 medical and health sciences
Organ Culture Techniques
Elastic Modulus
medicine
Animals
Humans
Regeneration
Collagen Type II
Wound Healing
Regeneration (biology)
Intervertebral disc
bioreactors
lcsh:RD1-811
Transplantation
Hydrogel
030104 developmental biology
chemistry
Cattle
lcsh:RC925-935
Ex vivo
Zdroj: European Cells & Materials, Vol 36, Pp 200-217 (2018)
ISSN: 1473-2262
Popis: Numerous studies show promise for cell-based tissue engineering strategies aiming to repair painful intervertebral disc (IVD) degeneration. However, clinical translation to human IVD repair is slow. In the present study, the regenerative potential of an autologous nucleus pulposus (NP)-cell-seeded thermoresponsive hyaluronic acid hydrogel in human lumbar IVDs was assessed under physiological conditions. First, agarose-encased in vitro constructs were developed, showing greater than 90 % NP cell viability and high proteoglycan deposition within HA-pNIPAM hydrogels following 3 weeks of dynamic loading. Second, a bovine-induced IVD degeneration model was used to optimise and validate T1ρ magnetic resonance imaging (MRI) for detection of changes in proteoglycan content in isolated intact IVDs. Finally, isolated intact human lumbar IVDs were pre-scanned using the established MRI sequence. Then, IVDs were injected with HA-pNIPAM hydrogel alone or autologous NP-cell-seeded. Next, the treated IVDs were cultured under cyclic dynamic loading for 5 weeks. Post-treatment T1ρ values were significantly higher as compared to pre-treatment scans within the same IVD and region of interest. Histological evaluation of treated human IVDs showed that the implanted hydrogel alone accumulated proteoglycans, while those that contained NP cells also displayed neo-matrix-surrounded cells within the gel. The study indicated a clinical potential for repairing early degenerative human IVDs using autologous cells/hydrogel suspensions. This unique IVD culture set-up, combined with the long-term physiological culture of intact human IVDs, allowed for a more clinically relevant evaluation of human tissue repair and regeneration, which otherwise could not be replicated using the available in vitro and in vivo models.
Databáze: OpenAIRE
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