Cargando…
In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams
Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolacton...
Autores principales: | , , , , , , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Springer Berlin Heidelberg
2022
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006054/ https://www.ncbi.nlm.nih.gov/pubmed/36309635 http://dx.doi.org/10.1007/s00418-022-02156-3 |
_version_ | 1784905227959271424 |
---|---|
author | Kokozidou, Maria Gögele, Clemens Pirrung, Felix Hammer, Niels Werner, Christian Kohl, Benjamin Hahn, Judith Breier, Annette Schröpfer, Michaela Meyer, Michael Schulze-Tanzil, Gundula |
author_facet | Kokozidou, Maria Gögele, Clemens Pirrung, Felix Hammer, Niels Werner, Christian Kohl, Benjamin Hahn, Judith Breier, Annette Schröpfer, Michaela Meyer, Michael Schulze-Tanzil, Gundula |
author_sort | Kokozidou, Maria |
collection | PubMed |
description | Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or F combined with the foam (F + coll). Cell-free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, cell vitality and content, histo(patho)logy of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed. Scaffolds did not affect mice weight development and organs, indicating no organ toxicity. Moreover, scaffolds maintained their size and shape and reflected a high cell viability prior to and following implantation. Coll or F + coll scaffolds seeded with cells yielded superior macroscopic properties compared to the controls. Mild signs of inflammation (foreign-body giant cells and hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable after explantation, elastic modulus, maximum force, tensile strength and strain at F(max) were significantly lower in explanted scaffolds compared to those before implantation, with no significant differences between scaffold subtypes, except for a higher maximum force in F + coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering. GRAPHICAL ABSTRACT: a Lapine anterior cruciate ligament (LACL): red arrow, posterior cruciate ligament: yellow arrow. Medial anterior meniscotibial ligament: black arrow. b Explant culture to isolate LACL fibroblasts. c Scaffold variants: co: controls; F: functionalization by gas-phase fluorination; coll: collagen foam cross-linked with hexamethylene diisocyanate (HMDI). c1-2 Embroidery pattern of the scaffolds. d Scaffolds were seeded with LACL fibroblasts using a dynamical culturing approach as depicted. e Scaffolds were implanted subnuchally into nude mice, fixed at the nuchal ligament and sacrospinal muscle tendons. f Two weeks after implantation. g Summary of analyses performed. Scale bars 1 cm (b, d), 0.5 cm (c). (sketches drawn by G.S.-T. using Krita 4.1.7 [Krita foundation, The Netherlands]). [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00418-022-02156-3. |
format | Online Article Text |
id | pubmed-10006054 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | Springer Berlin Heidelberg |
record_format | MEDLINE/PubMed |
spelling | pubmed-100060542023-03-12 In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams Kokozidou, Maria Gögele, Clemens Pirrung, Felix Hammer, Niels Werner, Christian Kohl, Benjamin Hahn, Judith Breier, Annette Schröpfer, Michaela Meyer, Michael Schulze-Tanzil, Gundula Histochem Cell Biol Original Paper Although autografts represent the gold standard for anterior cruciate ligament (ACL) reconstruction, tissue-engineered ACLs provide a prospect to minimize donor site morbidity and limited graft availability. This study characterizes the ligamentogenesis in embroidered poly(L-lactide-co-ε-caprolactone) (P(LA-CL)) / polylactic acid (PLA) constructs using a dynamic nude mice xenograft model. (P(LA-CL))/PLA scaffolds remained either untreated (co) or were functionalized by gas fluorination (F), collagen foam cross-linked with hexamethylene diisocyanate (HMDI) (coll), or F combined with the foam (F + coll). Cell-free constructs or those seeded for 1 week with lapine ACL ligamentocytes were implanted into nude mice for 12 weeks. Following explantation, cell vitality and content, histo(patho)logy of scaffolds (including organs: liver, kidney, spleen), sulphated glycosaminoglycan (sGAG) contents and biomechanical properties were assessed. Scaffolds did not affect mice weight development and organs, indicating no organ toxicity. Moreover, scaffolds maintained their size and shape and reflected a high cell viability prior to and following implantation. Coll or F + coll scaffolds seeded with cells yielded superior macroscopic properties compared to the controls. Mild signs of inflammation (foreign-body giant cells and hyperemia) were limited to scaffolds without collagen. Microscopical score values and sGAG content did not differ significantly. Although remaining stable after explantation, elastic modulus, maximum force, tensile strength and strain at F(max) were significantly lower in explanted scaffolds compared to those before implantation, with no significant differences between scaffold subtypes, except for a higher maximum force in F + coll compared with F samples (in vivo). Scaffold functionalization with fluorinated collagen foam provides a promising approach for ACL tissue engineering. GRAPHICAL ABSTRACT: a Lapine anterior cruciate ligament (LACL): red arrow, posterior cruciate ligament: yellow arrow. Medial anterior meniscotibial ligament: black arrow. b Explant culture to isolate LACL fibroblasts. c Scaffold variants: co: controls; F: functionalization by gas-phase fluorination; coll: collagen foam cross-linked with hexamethylene diisocyanate (HMDI). c1-2 Embroidery pattern of the scaffolds. d Scaffolds were seeded with LACL fibroblasts using a dynamical culturing approach as depicted. e Scaffolds were implanted subnuchally into nude mice, fixed at the nuchal ligament and sacrospinal muscle tendons. f Two weeks after implantation. g Summary of analyses performed. Scale bars 1 cm (b, d), 0.5 cm (c). (sketches drawn by G.S.-T. using Krita 4.1.7 [Krita foundation, The Netherlands]). [Image: see text] SUPPLEMENTARY INFORMATION: The online version contains supplementary material available at 10.1007/s00418-022-02156-3. Springer Berlin Heidelberg 2022-10-29 2023 /pmc/articles/PMC10006054/ /pubmed/36309635 http://dx.doi.org/10.1007/s00418-022-02156-3 Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) . |
spellingShingle | Original Paper Kokozidou, Maria Gögele, Clemens Pirrung, Felix Hammer, Niels Werner, Christian Kohl, Benjamin Hahn, Judith Breier, Annette Schröpfer, Michaela Meyer, Michael Schulze-Tanzil, Gundula In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams |
title | In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams |
title_full | In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams |
title_fullStr | In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams |
title_full_unstemmed | In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams |
title_short | In vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams |
title_sort | in vivo ligamentogenesis in embroidered poly(lactic-co-ε-caprolactone) / polylactic acid scaffolds functionalized by fluorination and hexamethylene diisocyanate cross-linked collagen foams |
topic | Original Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10006054/ https://www.ncbi.nlm.nih.gov/pubmed/36309635 http://dx.doi.org/10.1007/s00418-022-02156-3 |
work_keys_str_mv | AT kokozidoumaria invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT gogeleclemens invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT pirrungfelix invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT hammerniels invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT wernerchristian invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT kohlbenjamin invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT hahnjudith invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT breierannette invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT schropfermichaela invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT meyermichael invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams AT schulzetanzilgundula invivoligamentogenesisinembroideredpolylacticcoecaprolactonepolylacticacidscaffoldsfunctionalizedbyfluorinationandhexamethylenediisocyanatecrosslinkedcollagenfoams |