Tendon augmentation with a novel biomimetic polydioxanone patch: an in vivo biocompatibility study
<p><b>Introduction and Aims</b>: There is great interest in biomimetic devices to augment tendon repairs. Ideally, implants improve healing without causing adverse local or systemic reactions. Biocompatibility remains a critical issue prior to implantation into humans, as some impl...
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| Other Authors: | |
| Format: | Thesis |
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2013
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| _version_ | 1797098036142276608 |
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| author | Morrey, M |
| author2 | Carr, A |
| author_facet | Carr, A Morrey, M |
| author_sort | Morrey, M |
| collection | OXFORD |
| description | <p><b>Introduction and Aims</b>: There is great interest in biomimetic devices to augment tendon repairs. Ideally, implants improve healing without causing adverse local or systemic reactions. Biocompatibility remains a critical issue prior to implantation into humans, as some implants elicit a foreign body response (FBR) involving inflammation, poor wound healing and even fistulae formation. Any implant should maintain its tensile strength while tendon healing occurs. Additionally, the effect on articular cartilage locally or systemically with placement of juxta-articular implants has not been examined. The aim of this thesis is to test the <em>in vivo</em> biocompatibility and tensile strength of a novel hybrid woven and electrospun polydioxanone patch in a rat tendon transection model.</p> <p><b>Main Study Methods</b>: Sixty Lewis rats were divided into 4 groups in which the infraspinatus was surgically transected 3 mm from its insertion. Tendons were repaired with a laminated woven and electrospun polydioxanone patch (PDOe) and 5-0 polypropylene sutures. Polylactic-coglycolic acid (PGLA) and silk patches or a simple polypropylene suture repair served as comparators. Animals were sacrificed at 1, 2, 4, 6 and 12 weeks to examine the biocompatibility of the implants. Immunohistochemistry was used to examine macrophage subpopulations and hematoxylin and eosin staining was used to assess foreign-body giant cells (FBGC) and both analyzed with a two-way ANOVA with significance set at p&LT;.05. Articular cartilage was scrutinised with semi-quantitative analysis. Hind paw inflammatory indices were used to determine the systemic effects and biomechanical testing the tensile strength of the materials over time.</p> <p><b>Findings and Results</b>: The PDOe patch remained grossly quiescent at all time-points. There was a severe inflammatory reaction to Vicryl at one and 2-week time-points with a massive transudate. Silk patches were associated with larger fibrous capsules at each time point. There were no adverse systemic effects and articular cartilage remained normal with no differences between materials and controls. Immunohistochemistry showed a significantly higher ratio of inflammatory macrophages to total cells for the PGLA and silk patches compared to the PDOe patch and controls at each time-point except four weeks and no difference in regenerative macrophages across all time-points. Silk and Vicryl patches had a significantly greater number of FBGC’s compared to the PDOe patch and controls(p&LT;.05) at all time-points, again with the exception of 4 weeks, suggesting incorporation rather than rejection and walling off of the biomaterial. Tensile strength of the PDOe patch remained around 20N until 6-weeks and then gradually declined from 6 to 12-weeks.</p> <p><b>Discussion and Conclusions</b>: The novel PDOe patch appears to be biocompatible and illicit very little FBR in this rat tendon injury 4 model. Importantly, there was no joint reaction to the biomaterial, which has not been addressed previously. The electrospun component of the patch recapitulates native tendon architecture creating a tissue healing microenvironment directed by a regenerative macrophage subpopulation. These results corroborate earlier <em>in vitro</em> work that showed incorporation of tenocyte-like cells within the electrospun scaffold. The woven component of the scaffold provides tensile strength as the tendon heals and begins to degrade after healing is underway making it less likely to elicit a FBR. Based on these and earlier <em>in vitro</em> data we believe this implant shows excellent biocompatibility and is ready to proceed to human trials.</p> |
| first_indexed | 2024-03-07T05:03:54Z |
| format | Thesis |
| id | oxford-uuid:d943bd90-44da-4cce-ad0a-2b6eb453f925 |
| institution | University of Oxford |
| last_indexed | 2024-03-07T05:03:54Z |
| publishDate | 2013 |
| record_format | dspace |
| spelling | oxford-uuid:d943bd90-44da-4cce-ad0a-2b6eb453f9252022-03-27T08:54:36ZTendon augmentation with a novel biomimetic polydioxanone patch: an in vivo biocompatibility studyThesishttp://purl.org/coar/resource_type/c_bdccuuid:d943bd90-44da-4cce-ad0a-2b6eb453f925ORA Deposit2013Morrey, MCarr, AFranklin, SHakimi, O<p><b>Introduction and Aims</b>: There is great interest in biomimetic devices to augment tendon repairs. Ideally, implants improve healing without causing adverse local or systemic reactions. Biocompatibility remains a critical issue prior to implantation into humans, as some implants elicit a foreign body response (FBR) involving inflammation, poor wound healing and even fistulae formation. Any implant should maintain its tensile strength while tendon healing occurs. Additionally, the effect on articular cartilage locally or systemically with placement of juxta-articular implants has not been examined. The aim of this thesis is to test the <em>in vivo</em> biocompatibility and tensile strength of a novel hybrid woven and electrospun polydioxanone patch in a rat tendon transection model.</p> <p><b>Main Study Methods</b>: Sixty Lewis rats were divided into 4 groups in which the infraspinatus was surgically transected 3 mm from its insertion. Tendons were repaired with a laminated woven and electrospun polydioxanone patch (PDOe) and 5-0 polypropylene sutures. Polylactic-coglycolic acid (PGLA) and silk patches or a simple polypropylene suture repair served as comparators. Animals were sacrificed at 1, 2, 4, 6 and 12 weeks to examine the biocompatibility of the implants. Immunohistochemistry was used to examine macrophage subpopulations and hematoxylin and eosin staining was used to assess foreign-body giant cells (FBGC) and both analyzed with a two-way ANOVA with significance set at p&LT;.05. Articular cartilage was scrutinised with semi-quantitative analysis. Hind paw inflammatory indices were used to determine the systemic effects and biomechanical testing the tensile strength of the materials over time.</p> <p><b>Findings and Results</b>: The PDOe patch remained grossly quiescent at all time-points. There was a severe inflammatory reaction to Vicryl at one and 2-week time-points with a massive transudate. Silk patches were associated with larger fibrous capsules at each time point. There were no adverse systemic effects and articular cartilage remained normal with no differences between materials and controls. Immunohistochemistry showed a significantly higher ratio of inflammatory macrophages to total cells for the PGLA and silk patches compared to the PDOe patch and controls at each time-point except four weeks and no difference in regenerative macrophages across all time-points. Silk and Vicryl patches had a significantly greater number of FBGC’s compared to the PDOe patch and controls(p&LT;.05) at all time-points, again with the exception of 4 weeks, suggesting incorporation rather than rejection and walling off of the biomaterial. Tensile strength of the PDOe patch remained around 20N until 6-weeks and then gradually declined from 6 to 12-weeks.</p> <p><b>Discussion and Conclusions</b>: The novel PDOe patch appears to be biocompatible and illicit very little FBR in this rat tendon injury 4 model. Importantly, there was no joint reaction to the biomaterial, which has not been addressed previously. The electrospun component of the patch recapitulates native tendon architecture creating a tissue healing microenvironment directed by a regenerative macrophage subpopulation. These results corroborate earlier <em>in vitro</em> work that showed incorporation of tenocyte-like cells within the electrospun scaffold. The woven component of the scaffold provides tensile strength as the tendon heals and begins to degrade after healing is underway making it less likely to elicit a FBR. Based on these and earlier <em>in vitro</em> data we believe this implant shows excellent biocompatibility and is ready to proceed to human trials.</p> |
| spellingShingle | Morrey, M Tendon augmentation with a novel biomimetic polydioxanone patch: an in vivo biocompatibility study |
| title | Tendon augmentation with a novel biomimetic polydioxanone patch: an in vivo biocompatibility study |
| title_full | Tendon augmentation with a novel biomimetic polydioxanone patch: an in vivo biocompatibility study |
| title_fullStr | Tendon augmentation with a novel biomimetic polydioxanone patch: an in vivo biocompatibility study |
| title_full_unstemmed | Tendon augmentation with a novel biomimetic polydioxanone patch: an in vivo biocompatibility study |
| title_short | Tendon augmentation with a novel biomimetic polydioxanone patch: an in vivo biocompatibility study |
| title_sort | tendon augmentation with a novel biomimetic polydioxanone patch an in vivo biocompatibility study |
| work_keys_str_mv | AT morreym tendonaugmentationwithanovelbiomimeticpolydioxanonepatchaninvivobiocompatibilitystudy |