Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro
Focal cartilage defects caused by joint injury have a limited capacity to self-repair and, if left untreated, can lead to the early onset of osteoarthritis. The current standard of care, microfracture surgery, induces an endogenous repair response, but typically results in poorly integrated fibrocar...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Mary Ann Liebert Inc
2020
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| Online Access: | https://hdl.handle.net/1721.1/124763 |
| _version_ | 1811089144940593152 |
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| author | Liebesny, Paul H. Mroszczyk, Keri Zlotnick, Hannah Hung, Han-Hwa Frank, Eliot Grodzinsky, Alan J. |
| author2 | Massachusetts Institute of Technology. Department of Biological Engineering |
| author_facet | Massachusetts Institute of Technology. Department of Biological Engineering Liebesny, Paul H. Mroszczyk, Keri Zlotnick, Hannah Hung, Han-Hwa Frank, Eliot Grodzinsky, Alan J. |
| author_sort | Liebesny, Paul H. |
| collection | MIT |
| description | Focal cartilage defects caused by joint injury have a limited capacity to self-repair and, if left untreated, can lead to the early onset of osteoarthritis. The current standard of care, microfracture surgery, induces an endogenous repair response, but typically results in poorly integrated fibrocartilage, rather than native hyaline cartilage. The objective of this study was to test the hypothesis that a self-assembling peptide hydrogel functionalized with the proanabolic growth factor heparin-binding insulin-like growth factor-1 (HB-IGF-1) may improve integration between native cartilage and neotissue when combined with a brief enzymatic pretreatment to the defect site. This enzymatic pretreatment releases proteoglycans from the walls of the surrounding native cartilage in a controlled manner and, thereby, creates space for newly synthesized repair tissue to anchor and integrate with adjacent host cartilage. We used an in vitro model in which a cylindrical annulus of native cartilage was pretreated with trypsin over a 2-min period and then filled with a chondrocyte-seeded [KLDL]3 hydrogel functionalized with proanabolic HB-IGF-1 that had been premixed into the gel. This procedure was deemed to be clinically tractable in the context of ongoing parallel animal studies as a method to augment the microfracture procedure. The trypsin pretreatment depleted proteoglycan content of adjacent cartilage in a controlled manner without inducing cell death. The addition of HB-IGF-1 was found to stimulate matrix biosynthesis both in the surrounding cartilage and the chondrocyte-seeded KLD scaffold, and to enhance mechanical integration of neotissue into native matrix. A critical attribute for the long-term success of cartilage defect repair is the strong integration between the repair tissue and the surrounding native tissue. Current approaches utilized by physicians fail to achieve this attribute, leading to eventual relapse of the defect. This article demonstrates the concept of a simple, clinically viable approach for enhancing tissue integration via the combination of a safe, transient enzymatic treatment with a locally delivered, retained growth factor through an in vitro hydrogel/cartilage explant model. |
| first_indexed | 2024-09-23T14:14:24Z |
| format | Article |
| id | mit-1721.1/124763 |
| institution | Massachusetts Institute of Technology |
| language | English |
| last_indexed | 2024-09-23T14:14:24Z |
| publishDate | 2020 |
| publisher | Mary Ann Liebert Inc |
| record_format | dspace |
| spelling | mit-1721.1/1247632022-10-01T20:02:15Z Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro Liebesny, Paul H. Mroszczyk, Keri Zlotnick, Hannah Hung, Han-Hwa Frank, Eliot Grodzinsky, Alan J. Massachusetts Institute of Technology. Department of Biological Engineering Massachusetts Institute of Technology. Department of Mechanical Engineering Massachusetts Institute of Technology. Department of Electrical Engineering and Computer Science Biochemistry Bioengineering Biomaterials Biomedical Engineering Focal cartilage defects caused by joint injury have a limited capacity to self-repair and, if left untreated, can lead to the early onset of osteoarthritis. The current standard of care, microfracture surgery, induces an endogenous repair response, but typically results in poorly integrated fibrocartilage, rather than native hyaline cartilage. The objective of this study was to test the hypothesis that a self-assembling peptide hydrogel functionalized with the proanabolic growth factor heparin-binding insulin-like growth factor-1 (HB-IGF-1) may improve integration between native cartilage and neotissue when combined with a brief enzymatic pretreatment to the defect site. This enzymatic pretreatment releases proteoglycans from the walls of the surrounding native cartilage in a controlled manner and, thereby, creates space for newly synthesized repair tissue to anchor and integrate with adjacent host cartilage. We used an in vitro model in which a cylindrical annulus of native cartilage was pretreated with trypsin over a 2-min period and then filled with a chondrocyte-seeded [KLDL]3 hydrogel functionalized with proanabolic HB-IGF-1 that had been premixed into the gel. This procedure was deemed to be clinically tractable in the context of ongoing parallel animal studies as a method to augment the microfracture procedure. The trypsin pretreatment depleted proteoglycan content of adjacent cartilage in a controlled manner without inducing cell death. The addition of HB-IGF-1 was found to stimulate matrix biosynthesis both in the surrounding cartilage and the chondrocyte-seeded KLD scaffold, and to enhance mechanical integration of neotissue into native matrix. A critical attribute for the long-term success of cartilage defect repair is the strong integration between the repair tissue and the surrounding native tissue. Current approaches utilized by physicians fail to achieve this attribute, leading to eventual relapse of the defect. This article demonstrates the concept of a simple, clinically viable approach for enhancing tissue integration via the combination of a safe, transient enzymatic treatment with a locally delivered, retained growth factor through an in vitro hydrogel/cartilage explant model. National Institute of Arthritis and Musculoskeletal and Skin Diseases (U.S.) (Grant AR060331) 2020-04-21T17:45:52Z 2020-04-21T17:45:52Z 2019-09-01 2020-03-06T18:57:44Z Article http://purl.org/eprint/type/JournalArticle 1937-3341 1937-335X https://hdl.handle.net/1721.1/124763 Liebesny, Paul H. et al. “Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro.” Tissue engineering Part A 25 (2019): 1191-1201 © 2019 The Author(s) en 10.1089/ten.tea.2019.0013 Tissue engineering Article is made available in accordance with the publisher's policy and may be subject to US copyright law. Please refer to the publisher's site for terms of use. application/pdf Mary Ann Liebert Inc Mary Ann Liebert |
| spellingShingle | Biochemistry Bioengineering Biomaterials Biomedical Engineering Liebesny, Paul H. Mroszczyk, Keri Zlotnick, Hannah Hung, Han-Hwa Frank, Eliot Grodzinsky, Alan J. Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro |
| title | Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro |
| title_full | Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro |
| title_fullStr | Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro |
| title_full_unstemmed | Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro |
| title_short | Enzyme Pretreatment plus Locally Delivered HB-IGF-1 Stimulate Integrative Cartilage Repair In Vitro |
| title_sort | enzyme pretreatment plus locally delivered hb igf 1 stimulate integrative cartilage repair in vitro |
| topic | Biochemistry Bioengineering Biomaterials Biomedical Engineering |
| url | https://hdl.handle.net/1721.1/124763 |
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