Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

Willems, Nicole; Mihov, George; Grinwis, Guy C. M.; Dijk, M. Van; Schumann, Detlef; Bos, Clemens; Strijkers, Gustav J.; Dhert, Wouter J.A.; Meij, Björn P.; Creemers, Laura B.; Tryfonidou, Marianna A.

doi:10.1002/jbm.b.33579

Cited by 25 publications

(29 citation statements)

References 34 publications

(76 reference statements)

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“…Within the field of tissue engineering, several cell seeded hydrogels have been proposed to treat IVDD, which include replacement of the entire or part of the disc in in vivo or mainly for use as drug control release systems. Some examples are biocompatible hydrogels such as PCLA‐PEG‐PCLA (poly(ε‐caprolactone‐co‐lactide)‐b‐poly(ethylene glycol)‐bpoly(ε‐caprolactone‐co‐lactide)), agarose, and polyester amides . Additionally, hydrogels have also been used to encapsulate drugs for delivery into the IVD …”

Section: Experimental Studies Using the Canine Model—biological Stratmentioning

confidence: 99%

“…Some examples are biocompatible hydrogels such as PCLA‐PEG‐PCLA (poly(ε‐caprolactone‐co‐lactide)‐b‐poly(ethylene glycol)‐bpoly(ε‐caprolactone‐co‐lactide)), agarose, and polyester amides . Additionally, hydrogels have also been used to encapsulate drugs for delivery into the IVD …”

Section: Experimental Studies Using the Canine Model—biological Stratmentioning

confidence: 99%

“…Some examples are biocompatible hydrogels such as PCLA-PEG-PCLA (poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-bpoly(ε-caprolactone-co-lactide)), agarose, and polyester amides. [104][105][106] Additionally, hydrogels have also been used to encapsulate drugs for delivery into the IVD. [105][106][107] These various therapies, as summarized, demonstrate the potential of the CD dog model as a clinically relevant model to evaluate regenerative IVDD therapies which can later translate to human conditions.…”

Section: Ies the Canine Brief Pain Inventory (Cbpi) And The Helsinkimentioning

confidence: 99%

“…[104][105][106] Additionally, hydrogels have also been used to encapsulate drugs for delivery into the IVD. [105][106][107] These various therapies, as summarized, demonstrate the potential of the CD dog model as a clinically relevant model to evaluate regenerative IVDD therapies which can later translate to human conditions. However, unexplored is the potential of using organ culture as a tool to investigate and screen biological therapies for IVDD.…”

Section: Ies the Canine Brief Pain Inventory (Cbpi) And The Helsinkimentioning

confidence: 99%

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The chondrodystrophic dog: A clinically relevant intermediate‐sized animal model for the study of intervertebral disc‐associated spinal pain

et al. 2018

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Low back pain (LBP) is the leading cause of disability worldwide, with an estimated 80% of the American population suffering from a painful back condition at some point during their lives. The most common cause of LBP is intervertebral disc (IVD) degeneration (IVDD), a condition that can be difficult to treat, either surgically or medically, with current available therapies. Thus, understanding the pathological mechanisms of IVDD and developing novel treatments are critical for improving outcome and quality of life in people living with LBP. While experimental animal models provide valuable mechanistic insight, each model has limitations that complicate translation to the clinical setting. This review focuses on the chondrodystrophic canine clinical model of IVDD as a promising model to assess IVD‐associated spinal pain and translational therapeutic strategies for LBP. The canine IVD, while smaller in size than human, goat, ovine, and bovine IVDs, is larger than most other small animal IVDD models and undergoes maturational changes similar to those of the human IVD. Furthermore, both dogs and humans develop painful IVDD as a spontaneous process, resulting in similar characteristic pathologies and clinical signs. Future exploration of the canine model as a model of IVD‐associated spinal pain and biological treatments using the canine clinical model will further demonstrate its translational capabilities with the added ethical benefit of treating an existing veterinary patient population with IVDD.

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Section: Experimental Studies Using the Canine Model—biological Stratmentioning

confidence: 99%

Section: Experimental Studies Using the Canine Model—biological Stratmentioning

confidence: 99%

Section: Ies the Canine Brief Pain Inventory (Cbpi) And The Helsinkimentioning

confidence: 99%

Section: Ies the Canine Brief Pain Inventory (Cbpi) And The Helsinkimentioning

confidence: 99%

See 2 more Smart Citations

The chondrodystrophic dog: A clinically relevant intermediate‐sized animal model for the study of intervertebral disc‐associated spinal pain

et al. 2018

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“…Six animals were sacrificed 7 days after injection, and six after 28 days, resulting in n = 3 implantation sites per . A detailed description of the procedure has been published elsewhere (Willems, Bach, et al, 2015;Willems, Mihov, et al, 2015). Briefly, dogs were positioned in right recumbent position to expose the nine IVDs betweenT12 and L6 via a left lateral approach, and the L6-L7 and L7-S1 IVDs via a mini-dorsal laminectomy.…”

Section: In Vivo Biocompatibility After Subcutaneous Injection In Micementioning

confidence: 99%

Intradiscal application of a PCLA–PEG–PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

Tellegen

Willems

Beukers

et al. 2017

J Tissue Eng Regen Med

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Chronic low back pain is a common clinical problem in both the human and canine population. Current pharmaceutical treatment often consists of oral anti-inflammatory drugs to alleviate pain. Novel treatments for degenerative disc disease focus on local application of sustained released drug formulations. The aim of this study was to determine safety and feasibility of intradiscal application of a poly(ε-caprolactone-co-lactide)-b-poly(ethylene glycol)-bpoly(ε-caprolactone-co-lactide) PCLA-PEG-PCLA hydrogel releasing celecoxib, a COX-2 inhibitor. Biocompatibility was evaluated after subcutaneous injection in mice, and safety of intradiscal injection of the hydrogel was evaluated in experimental dogs with early spontaneous intervertebral disc (IVD) degeneration. COX-2 expression was increased in IVD samples surgically obtained from canine patients, indicating a role of COX-2 in clinical IVD disease. Ten client-owned dogs with chronic low back pain related to IVD degeneration received an intradiscal injection with the celecoxib-loaded hydrogel. None of the dogs showed adverse reactions after intradiscal injection. The hydrogel did not influence magnetic resonance imaging signal at long-term follow-up. Clinical improvement was achieved by reduction of back pain in 9 of 10 dogs, as was shown by clinical examination and owner questionnaires. In 3 of 10 dogs, back pain recurred after 3 months. This study showed the safety and effectiveness of intradiscal injections in vivo with a thermoresponsive PCLA-PEG-PCLA hydrogel loaded with celecoxib. In this set-up, the dog can be used as a model for the development of novel treatment modalities in both canine and human patients with chronic low back pain.

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Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical

et al. 2018

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Chronic back and neck pain is a prevalent disability, often caused by degeneration of the intervertebral disc. Because current treatments for this condition are less than satisfactory, a great deal of effort is being applied to develop new solutions, including regenerative strategies. However, the path from initial promising idea to clinical use is fraught with many hurdles to overcome. Many of the keys to success are not necessarily linked to science or innovation. Successful translation to clinic will also rely on planning and awareness of the hurdles. It will be essential to plan your entire path to clinic from the outset and to do this with a multidisciplinary team. Take advice early on regulatory aspects and focus on generating the proof required to satisfy regulatory approval. Scientific demonstration and societal benefits are important, but translation cannot occur without involving commercial parties, which are instrumental to support expensive clinical trials. This will only be possible when intellectual property can be protected sufficiently to support a business model. In this manner, commercial, societal, medical, and scientific partners can work together to ultimately improve patient health. Based on literature surveys and experiences of the co‐authors, this opinion paper presents this pathway, highlights the most prominent issues and hopefully will aid in your own translational endeavors.

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Safety of intradiscal injection and biocompatibility of polyester amide microspheres in a canine model predisposed to intervertebral disc degeneration

Cited by 25 publications

References 34 publications

The chondrodystrophic dog: A clinically relevant intermediate‐sized animal model for the study of intervertebral disc‐associated spinal pain

The chondrodystrophic dog: A clinically relevant intermediate‐sized animal model for the study of intervertebral disc‐associated spinal pain

Intradiscal application of a PCLA–PEG–PCLA hydrogel loaded with celecoxib for the treatment of back pain in canines: What's in it for humans?

Leaping the hurdles in developing regenerative treatments for the intervertebral disc from preclinical to clinical

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