In vitro and in vivo performance of methacrylated gellan gum hydrogel formulations for cartilage repair
Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic...
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| Published in | Journal of biomedical materials research. Part A Vol. 106; no. 7; pp. 1987 - 1996 |
|---|---|
| Main Authors | , , , , , , , , , , , , |
| Format | Journal Article |
| Language | English |
| Published |
United States
Wiley Subscription Services, Inc
01.07.2018
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| Subjects | |
| Online Access | Get full text |
| ISSN | 1549-3296 1552-4965 1552-4965 |
| DOI | 10.1002/jbm.a.36406 |
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| Abstract | Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof‐of‐concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non‐treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non‐treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno‐free biomaterial to be used with chondrogenic cells for a cost‐effective treatment of focal chondral lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1987–1996, 2018 |
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| AbstractList | Methacrylated gellan gum (GGMA) formulation is proposed as a second-generation hydrogel for controlled delivery of cartilage-forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof-of-concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non-treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non-treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno-free biomaterial to be used with chondrogenic cells for a cost-effective treatment of focal chondral lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1987-1996, 2018.Methacrylated gellan gum (GGMA) formulation is proposed as a second-generation hydrogel for controlled delivery of cartilage-forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof-of-concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non-treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non-treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno-free biomaterial to be used with chondrogenic cells for a cost-effective treatment of focal chondral lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1987-1996, 2018. Methacrylated gellan gum (GGMA) formulation is proposed as a second-generation hydrogel for controlled delivery of cartilage-forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof-of-concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non-treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non-treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno-free biomaterial to be used with chondrogenic cells for a cost-effective treatment of focal chondral lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1987-1996, 2018. Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof‐of‐concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non‐treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo, this formulation promoted significantly superior de novo cartilage formation compared with the non‐treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo, positioning itself as an attractive xeno‐free biomaterial to be used with chondrogenic cells for a cost‐effective treatment of focal chondral lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1987–1996, 2018 Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral lesions, allowing immediate in situ retention of cells and 3D filling of lesion volume, such approach deemed compatible with an arthroscopic procedure. Formulation optimization was carried out in vitro using chondrocytes and adipose mesenchymal stromal/stem cells (ASCs). A proof‐of‐concept in vivo study was conducted using a rabbit model with induced chondral lesions. Outcomes were compared with microfracture or non‐treated control. Three grading scores were used to evaluate tissue repair after 8 weeks by macroscopic, histological and immunohistochemical analysis. Intense collagen type II and low collagen type I gene and protein expression were achieved in vitro by the ASC + GGMA formulation, in light with development of healthy chondral tissue. In vivo , this formulation promoted significantly superior de novo cartilage formation compared with the non‐treated group. Maintenance of chondral height and integration with native tissue was further accomplished. The physicochemical properties of the proposed GGMA hydrogel exhibited highly favorable characteristics and biological performance both in vitro and in vivo , positioning itself as an attractive xeno‐free biomaterial to be used with chondrogenic cells for a cost‐effective treatment of focal chondral lesions. © 2018 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 106A: 1987–1996, 2018 |
| Author | da Silva Morais, Alain Reis, Rui L. Learmonth, David A. Oliveira, Pedro Moreira, Elsa S. Gertrudes, Ana C. Oliveira, Joaquim M. Santos, Tírcia C. Espregueira‐Mendes, João D. Vilela, Carlos A. Correia, Cristina Sousa, Rui A. Frias, Ana M. |
| Author_xml | – sequence: 1 givenname: Carlos A. orcidid: 0000-0002-1680-4498 surname: Vilela fullname: Vilela, Carlos A. email: cvilelagomes@gmail.com organization: Hospital da Senhora da Oliveira Guimarães EPE – sequence: 2 givenname: Cristina surname: Correia fullname: Correia, Cristina organization: Stemmatters, Biotecnologia e Medicina Regenerativa SA – sequence: 3 givenname: Alain surname: da Silva Morais fullname: da Silva Morais, Alain organization: ICVS/3Bs–PT Government Associate Laboratory – sequence: 4 givenname: Tírcia C. orcidid: 0000-0002-5365-4863 surname: Santos fullname: Santos, Tírcia C. organization: ICVS/3Bs–PT Government Associate Laboratory – sequence: 5 givenname: Ana C. surname: Gertrudes fullname: Gertrudes, Ana C. organization: Stemmatters, Biotecnologia e Medicina Regenerativa SA – sequence: 6 givenname: Elsa S. surname: Moreira fullname: Moreira, Elsa S. organization: Stemmatters, Biotecnologia e Medicina Regenerativa SA – sequence: 7 givenname: Ana M. surname: Frias fullname: Frias, Ana M. organization: Stemmatters, Biotecnologia e Medicina Regenerativa SA – sequence: 8 givenname: David A. surname: Learmonth fullname: Learmonth, David A. organization: Stemmatters, Biotecnologia e Medicina Regenerativa SA – sequence: 9 givenname: Pedro surname: Oliveira fullname: Oliveira, Pedro organization: ISUP‐EPI Unit, Institute of Biomedical Sciences Abel Salazar (ICBAS), University of Porto – sequence: 10 givenname: Joaquim M. surname: Oliveira fullname: Oliveira, Joaquim M. organization: ICVS/3Bs–PT Government Associate Laboratory – sequence: 11 givenname: Rui A. surname: Sousa fullname: Sousa, Rui A. organization: Stemmatters, Biotecnologia e Medicina Regenerativa SA – sequence: 12 givenname: João D. surname: Espregueira‐Mendes fullname: Espregueira‐Mendes, João D. organization: Clínica do Dragão, Espregueira‐Mendes Sports Centre, FIFA Medical Centre of Excellence and D. Henrique Research Centre – sequence: 13 givenname: Rui L. surname: Reis fullname: Reis, Rui L. organization: ICVS/3Bs–PT Government Associate Laboratory |
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| Snippet | Methacrylated gellan gum (GGMA) formulation is proposed as a second‐generation hydrogel for controlled delivery of cartilage‐forming cells into focal chondral... Methacrylated gellan gum (GGMA) formulation is proposed as a second-generation hydrogel for controlled delivery of cartilage-forming cells into focal chondral... |
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| SubjectTerms | adipose stromal/stem cells Biomaterials Cartilage cartilage repair Chondrocytes Collagen Collagen (type I) Collagen (type II) Evaluation Formulations Gellan gum Gene expression hydrogel Hydrogels In vivo methods and tests Lesions Mesenchyme methacrylated gellan gum Microfracture Physicochemical properties Proteins Repair Stem cells |
| Title | In vitro and in vivo performance of methacrylated gellan gum hydrogel formulations for cartilage repair |
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