Skip to main content
Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy 6/2019

01.11.2018 | EXPERIMENTAL STUDY

Agili-C implant promotes the regenerative capacity of articular cartilage defects in an ex vivo model

verfasst von: Susan Chubinskaya, Berardo Di Matteo, Laura Lovato, Francesco Iacono, Dror Robinson, Elizaveta Kon

Erschienen in: Knee Surgery, Sports Traumatology, Arthroscopy | Ausgabe 6/2019

Einloggen, um Zugang zu erhalten

Abstract

Purpose

Osteochondral implants are currently adopted for the treatment of symptomatic full-thickness chondral and osteochondral defects. Agili-C™ is a cell-free aragonite-based scaffold which aims to reproduce the original structure and function of the articular joint while directing the growth and regeneration of both cartilage and its underlying subchondral bone. The goal of the present study was to investigate the ex vivo mechanisms of action (MOA) of the Agili-C™ implant in the repair of full-thickness cartilage defects. In particular, we tested whether Agili-C™ implant has the potential to stimulate cartilage ingrowth through chondrocytes migration into the 3D interconnected porous structure of the scaffold, along with maintaining their viability and phenotype and the deposition of hyaline cartilage matrix.

Methods

Articular cartilage samples were collected through the Gift of Hope Organ and Tissue Donor Network (Itasca, IL) within 24 h from death. For this study, cartilage from a total of 14 donors was used. To model a chondral defect, donut-shaped cartilage explants were prepared from each tissue specimen. The chondral phase of the Agili-C™ implant was placed inside the tissue in full contact and press fit manner. Cartilage explants with the Agili-C™ implant inside were cultured for 60 days. As a control, the same donut-shaped cartilage explants were cultured without Agili-C™, under the same culture conditions.

Results

Using fresh human cadaveric articular cartilage tissue in a 60-day culture, it was demonstrated that chondrocytes were able to migrate into the Agili-C™ scaffold and contribute to the deposition of the extracellular matrix (ECM) rich in collagen type II and aggrecan, and lacking collagen type I. Additionally, we were able to show the formation of a layer populated by progenitor-like cells on the articular surface of the implant.

Conclusions

The analysis of samples taken from knee and ankle joints of human donors with a wide age range and both genders supports the potential of Agili-C™ scaffold to stimulate cartilage regeneration and repair. Based on these results, the present scaffold can be used in the clinical practice as a one-step procedure to treat full-thickness chondral defects.
Literatur
1.
Zurück zum Zitat Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ (2015) Osteoarthr Lancet 386(9991):376–387CrossRef Glyn-Jones S, Palmer AJ, Agricola R, Price AJ, Vincent TL, Weinans H, Carr AJ (2015) Osteoarthr Lancet 386(9991):376–387CrossRef
2.
Zurück zum Zitat Einhorn T, O’Keefe R, Chu C, Jacobs JJ (2013) American Academy of Orthopaedic Surgeons. Rosemont Ill Chap 10:183–198 Einhorn T, O’Keefe R, Chu C, Jacobs JJ (2013) American Academy of Orthopaedic Surgeons. Rosemont Ill Chap 10:183–198
3.
Zurück zum Zitat Perdisa F, Filardo G, Di Matteo B, Marcacci M, Kon E (2014) Platelet rich plasma: a valid augmentation for cartilage scaffolds? A systematic review. Histol Histopathol 29(7):805–814PubMed Perdisa F, Filardo G, Di Matteo B, Marcacci M, Kon E (2014) Platelet rich plasma: a valid augmentation for cartilage scaffolds? A systematic review. Histol Histopathol 29(7):805–814PubMed
4.
Zurück zum Zitat Kon E, Filardo G, Shani J, Altschuler N, Levy A, Zaslav K, Eisman JE, Robinson D (2015) Osteochondral regeneration with a novel aragonite-hyaluronate biphasic scaffold: up to 12-month follow-up study in a goat model. J Orthop Surg Res 10:81CrossRefPubMedPubMedCentral Kon E, Filardo G, Shani J, Altschuler N, Levy A, Zaslav K, Eisman JE, Robinson D (2015) Osteochondral regeneration with a novel aragonite-hyaluronate biphasic scaffold: up to 12-month follow-up study in a goat model. J Orthop Surg Res 10:81CrossRefPubMedPubMedCentral
5.
Zurück zum Zitat Kon E, Robinson D, Verdonk P, Drobnic M, Patrascu JM, Dulic O, Gavrilovic G, Filardo G (2016) A novel aragonite-based scaffold for osteochondral regeneration: early experience on human implants and technical developments. Injury 47(6):S27–S32CrossRefPubMed Kon E, Robinson D, Verdonk P, Drobnic M, Patrascu JM, Dulic O, Gavrilovic G, Filardo G (2016) A novel aragonite-based scaffold for osteochondral regeneration: early experience on human implants and technical developments. Injury 47(6):S27–S32CrossRefPubMed
6.
Zurück zum Zitat Hattori S, Oxford C, Reddi AH (2007) Identification of superficial zone articular chondrocyte stem/progenitor cells. Biochem Biophys Res Commun 358:99–103CrossRefPubMedPubMedCentral Hattori S, Oxford C, Reddi AH (2007) Identification of superficial zone articular chondrocyte stem/progenitor cells. Biochem Biophys Res Commun 358:99–103CrossRefPubMedPubMedCentral
7.
Zurück zum Zitat Dowthwaite GP, Bishop JC, Redman SN, Khan IM, Rooney P, Evans DJ, Haughton L, Bayram Z, Boyer S, Thomson B, Wolfe MS, Archer CW (2004) The surface of articular cartilage contains a progenitor cell population. J Cell Sci 117(Pt 6):889–897CrossRefPubMed Dowthwaite GP, Bishop JC, Redman SN, Khan IM, Rooney P, Evans DJ, Haughton L, Bayram Z, Boyer S, Thomson B, Wolfe MS, Archer CW (2004) The surface of articular cartilage contains a progenitor cell population. J Cell Sci 117(Pt 6):889–897CrossRefPubMed
8.
Zurück zum Zitat Grogan SP, Miyaki S, Asahara H, D’Lima DD, Lotz MK (2009) Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis. Arthritis Res Ther 11:R85CrossRefPubMedPubMedCentral Grogan SP, Miyaki S, Asahara H, D’Lima DD, Lotz MK (2009) Mesenchymal progenitor cell markers in human articular cartilage: normal distribution and changes in osteoarthritis. Arthritis Res Ther 11:R85CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Karlsson C, Lindahl A (2009) Articular cartilage stem cells signaling. Arthritis Res Therapy 11:121CrossRef Karlsson C, Lindahl A (2009) Articular cartilage stem cells signaling. Arthritis Res Therapy 11:121CrossRef
10.
Zurück zum Zitat Bos PK, Kops N, Verhaar JA et al (2008) Cellular origin of neocartilage formed at wound edges of articular cartilage in a tissue culture experiment. Osteoarthr Cartil 16:204–211CrossRef Bos PK, Kops N, Verhaar JA et al (2008) Cellular origin of neocartilage formed at wound edges of articular cartilage in a tissue culture experiment. Osteoarthr Cartil 16:204–211CrossRef
11.
Zurück zum Zitat Chandrasekhar S, Esterman MA, Hoffman HA (1987) Microdetermination of proteoglycans and glycosaminoglycans in the presence of guanidine hydrochloride. Anal Biochem 161:103–108CrossRefPubMed Chandrasekhar S, Esterman MA, Hoffman HA (1987) Microdetermination of proteoglycans and glycosaminoglycans in the presence of guanidine hydrochloride. Anal Biochem 161:103–108CrossRefPubMed
12.
Zurück zum Zitat Petit B, Masuda K, D’Souza AL, Otten L, Pietryla D, Hartmann DJ et al (1996) Characterization of crosslinked collagens synthesized by mature articular chondrocytes cultured in alginate beads: comparison of two distinct matrix compartments. Exp Cell Res 225:151–161CrossRefPubMed Petit B, Masuda K, D’Souza AL, Otten L, Pietryla D, Hartmann DJ et al (1996) Characterization of crosslinked collagens synthesized by mature articular chondrocytes cultured in alginate beads: comparison of two distinct matrix compartments. Exp Cell Res 225:151–161CrossRefPubMed
13.
Zurück zum Zitat Masuda K, Shirota H, Thonar EJ (1994) Quantification of 35S-labeled proteoglycans complexed to alcian blue by rapid filtration in multiwell plates. Anal Biochem 217:167–175CrossRefPubMed Masuda K, Shirota H, Thonar EJ (1994) Quantification of 35S-labeled proteoglycans complexed to alcian blue by rapid filtration in multiwell plates. Anal Biochem 217:167–175CrossRefPubMed
14.
Zurück zum Zitat Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real time quantitative PCT and the 2−∆∆CT method. Methods 25:402–408CrossRefPubMed Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real time quantitative PCT and the 2−∆∆CT method. Methods 25:402–408CrossRefPubMed
15.
Zurück zum Zitat Calloni R, Cordero EAA, Henriques J-A-P, Bonatto D (2013) Reviewing and updating the major molecular markers for stem cells. Stem Cells Dev 22(9):1455–1476CrossRefPubMedPubMedCentral Calloni R, Cordero EAA, Henriques J-A-P, Bonatto D (2013) Reviewing and updating the major molecular markers for stem cells. Stem Cells Dev 22(9):1455–1476CrossRefPubMedPubMedCentral
16.
Zurück zum Zitat Cavallo C, Schiavinato A, Secchieri C, Kon E, Filardo G, Paro M, Grigolo B (2018) Short-term homing of hyaluronan-primed cells: therapeutic implications for osteoarthritis treatment. Tissue Eng Part C Methods 24(2):121–133 , CrossRefPubMed Cavallo C, Schiavinato A, Secchieri C, Kon E, Filardo G, Paro M, Grigolo B (2018) Short-term homing of hyaluronan-primed cells: therapeutic implications for osteoarthritis treatment. Tissue Eng Part C Methods 24(2):121–133 , CrossRefPubMed
17.
Zurück zum Zitat Kon E, Filardo G, Robinson D, Eisman JA, Levy A, Zaslav K, Shani J, Altschuler N (2014) Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model. Knee Surg Sports Traumatol Arthrosc 22(6):1452–1464CrossRefPubMed Kon E, Filardo G, Robinson D, Eisman JA, Levy A, Zaslav K, Shani J, Altschuler N (2014) Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model. Knee Surg Sports Traumatol Arthrosc 22(6):1452–1464CrossRefPubMed
19.
Zurück zum Zitat Sofu H, Camurcu Y, Ucpunar H, Ozcan S, Yurten H, Sahin V (2018) Clinical and radiographic outcomes of chitosan-glycerol phosphate/blood implant are similar with hyaluronic acid-based cell-free scaffold in the treatment of focal osteochondral lesions of the knee joint. Knee Surg Sports Traumatol Arthrosc. https://doi.org/10.1007/s00167-018-5079-z CrossRefPubMed Sofu H, Camurcu Y, Ucpunar H, Ozcan S, Yurten H, Sahin V (2018) Clinical and radiographic outcomes of chitosan-glycerol phosphate/blood implant are similar with hyaluronic acid-based cell-free scaffold in the treatment of focal osteochondral lesions of the knee joint. Knee Surg Sports Traumatol Arthrosc. https://​doi.​org/​10.​1007/​s00167-018-5079-z CrossRefPubMed
20.
Zurück zum Zitat Dhollander AAM, Liekens K, Almqvist KF, Verdonk R, Lambrecht S, Elewaut D, Verbruggen G, Verdonk PC (2012) A pilot study of the use of an osteochondral scaffold plug for cartilage repair in the knee and how to deal with early clinical failures. Arthroscopy 28(2):225–233CrossRefPubMed Dhollander AAM, Liekens K, Almqvist KF, Verdonk R, Lambrecht S, Elewaut D, Verbruggen G, Verdonk PC (2012) A pilot study of the use of an osteochondral scaffold plug for cartilage repair in the knee and how to deal with early clinical failures. Arthroscopy 28(2):225–233CrossRefPubMed
21.
Zurück zum Zitat Kon E, Delcogliano M, Filardo G, Fini M, Giavaresi G, Francioli S, Martin I, Pressato D, Arcangeli E, Quarto R, Sandri M, Marcacci M (2010) Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial. J Orthop Res 28(1):116–124PubMed Kon E, Delcogliano M, Filardo G, Fini M, Giavaresi G, Francioli S, Martin I, Pressato D, Arcangeli E, Quarto R, Sandri M, Marcacci M (2010) Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial. J Orthop Res 28(1):116–124PubMed
22.
Zurück zum Zitat Verhaegen J, Clockaerts S, Van Osch GJ, Somville J, Verdonk P, Mertens P (2015) TruFit plug for repair of osteochondral defects—where is the evidence? Systematic review of literature. Cartilage 6(1):12–19CrossRefPubMedPubMedCentral Verhaegen J, Clockaerts S, Van Osch GJ, Somville J, Verdonk P, Mertens P (2015) TruFit plug for repair of osteochondral defects—where is the evidence? Systematic review of literature. Cartilage 6(1):12–19CrossRefPubMedPubMedCentral
23.
Zurück zum Zitat Joshi N, Reverte-Vinaixa M, Diaz-Ferreiro EW, Dominguez Oronoz R (2012) Synthetic resorbable scaffolds for the treatment of isolated patellofemoral cartilage defects in young patients: magnetic resonance imaging and clinical evaluation. Am J Sports Med 40(6):1289–1295CrossRefPubMed Joshi N, Reverte-Vinaixa M, Diaz-Ferreiro EW, Dominguez Oronoz R (2012) Synthetic resorbable scaffolds for the treatment of isolated patellofemoral cartilage defects in young patients: magnetic resonance imaging and clinical evaluation. Am J Sports Med 40(6):1289–1295CrossRefPubMed
24.
Zurück zum Zitat Mathis DT, Kaelin R, Rasch H, Arnold MP, Hirschmann MT (2018) Good clinical results but moderate osseointegration and defect filling of a cell-free multi-layered nano-composite scaffold for treatment of osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 26(4):1273–1280PubMed Mathis DT, Kaelin R, Rasch H, Arnold MP, Hirschmann MT (2018) Good clinical results but moderate osseointegration and defect filling of a cell-free multi-layered nano-composite scaffold for treatment of osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc 26(4):1273–1280PubMed
25.
Zurück zum Zitat Chubinskaya S, Malfait AM, Wimmer MA (2013) Form and function of articular cartilage. In: Einhorn T, O'Keefe R, Chu C, Jacobs JJ (eds) Orthopaedic basic science: foundation of clinical practice, 4th edn. American Academy of Orthopaedic Surgeons, Rosemont, Illinois, pp 183–198 Chubinskaya S, Malfait AM, Wimmer MA (2013) Form and function of articular cartilage. In: Einhorn T, O'Keefe R, Chu C, Jacobs JJ (eds) Orthopaedic basic science: foundation of clinical practice, 4th edn. American Academy of Orthopaedic Surgeons, Rosemont, Illinois, pp 183–198
26.
Zurück zum Zitat Angele P, Yoo JU, Smith C, Mansour J, Jepsen KJ, Nerlich M et al (2003) Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res 21:451–457CrossRefPubMed Angele P, Yoo JU, Smith C, Mansour J, Jepsen KJ, Nerlich M et al (2003) Cyclic hydrostatic pressure enhances the chondrogenic phenotype of human mesenchymal progenitor cells differentiated in vitro. J Orthop Res 21:451–457CrossRefPubMed
27.
Zurück zum Zitat Heyland J, Wiegandt K, Goepfert C, Nagel-Heyer S, Ilinich E, Schumacher U, Pörtner R (2006) Redifferentiation of chondrocytes and cartilage formation under intermittent hydrostatic pressure. Biotechnol Lett 28(20):1641–1648CrossRefPubMed Heyland J, Wiegandt K, Goepfert C, Nagel-Heyer S, Ilinich E, Schumacher U, Pörtner R (2006) Redifferentiation of chondrocytes and cartilage formation under intermittent hydrostatic pressure. Biotechnol Lett 28(20):1641–1648CrossRefPubMed
28.
Zurück zum Zitat Huang CY, Hagar KL, Frost LE, Sun Y, Cheung HS (2004) Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells 22:313–323CrossRefPubMed Huang CY, Hagar KL, Frost LE, Sun Y, Cheung HS (2004) Effects of cyclic compressive loading on chondrogenesis of rabbit bone-marrow derived mesenchymal stem cells. Stem Cells 22:313–323CrossRefPubMed
29.
Zurück zum Zitat Saha S, Ji L, de Pablo JJ, Palecek SP (2006) Inhibition of human embryonic stem cell differentiation by mechanical strain. J Cell Physiol 206:126–137CrossRefPubMed Saha S, Ji L, de Pablo JJ, Palecek SP (2006) Inhibition of human embryonic stem cell differentiation by mechanical strain. J Cell Physiol 206:126–137CrossRefPubMed
30.
Zurück zum Zitat Schumann D, Kujat R, Nerlich M, Angele P (2006) Mechanobiological conditioning of stem cells for cartilage tissue engineering. Biomed Mater Eng 16:S37–S52PubMed Schumann D, Kujat R, Nerlich M, Angele P (2006) Mechanobiological conditioning of stem cells for cartilage tissue engineering. Biomed Mater Eng 16:S37–S52PubMed
31.
Zurück zum Zitat Horbert V, Xin L, Foehr P, Brinkmann O, Bungartz M, Burgkart RH, Graeve T, Kinne RW (2018) In vitro analysis of cartilage regeneration using a collagen type I hydrogel (CaReS) in the bovine cartilage punch model. Cartilage 1:18 Horbert V, Xin L, Foehr P, Brinkmann O, Bungartz M, Burgkart RH, Graeve T, Kinne RW (2018) In vitro analysis of cartilage regeneration using a collagen type I hydrogel (CaReS) in the bovine cartilage punch model. Cartilage 1:18
32.
Zurück zum Zitat Dang Y, Cole AA, Homandberg GA (2003) Comparison of the catabolic effects of fibronectin fragments in human knee and ankle cartilages. Osteoarthr Cartil 11(7):538–547CrossRef Dang Y, Cole AA, Homandberg GA (2003) Comparison of the catabolic effects of fibronectin fragments in human knee and ankle cartilages. Osteoarthr Cartil 11(7):538–547CrossRef
33.
Zurück zum Zitat Eger W, Schumacher BL, Mollenhauer J, Kuettner KE, Cole AA (2002) Human knee and ankle cartilage explants: catabolic differences. J Orthop Res 20(3):526–534CrossRefPubMed Eger W, Schumacher BL, Mollenhauer J, Kuettner KE, Cole AA (2002) Human knee and ankle cartilage explants: catabolic differences. J Orthop Res 20(3):526–534CrossRefPubMed
Metadaten
Titel
Agili-C implant promotes the regenerative capacity of articular cartilage defects in an ex vivo model
verfasst von
Susan Chubinskaya
Berardo Di Matteo
Laura Lovato
Francesco Iacono
Dror Robinson
Elizaveta Kon
Publikationsdatum
01.11.2018
Verlag
Springer Berlin Heidelberg
Erschienen in
Knee Surgery, Sports Traumatology, Arthroscopy / Ausgabe 6/2019
Print ISSN: 0942-2056
Elektronische ISSN: 1433-7347
DOI
https://doi.org/10.1007/s00167-018-5263-1

Weitere Artikel der Ausgabe 6/2019

Knee Surgery, Sports Traumatology, Arthroscopy 6/2019 Zur Ausgabe

Arthropedia

Grundlagenwissen der Arthroskopie und Gelenkchirurgie. Erweitert durch Fallbeispiele, Videos und Abbildungen. 
» Jetzt entdecken

Notfall-TEP der Hüfte ist auch bei 90-Jährigen machbar

26.04.2024 Hüft-TEP Nachrichten

Ob bei einer Notfalloperation nach Schenkelhalsfraktur eine Hemiarthroplastik oder eine totale Endoprothese (TEP) eingebaut wird, sollte nicht allein vom Alter der Patientinnen und Patienten abhängen. Auch über 90-Jährige können von der TEP profitieren.

Arthroskopie kann Knieprothese nicht hinauszögern

25.04.2024 Gonarthrose Nachrichten

Ein arthroskopischer Eingriff bei Kniearthrose macht im Hinblick darauf, ob und wann ein Gelenkersatz fällig wird, offenbar keinen Unterschied.

Therapiestart mit Blutdrucksenkern erhöht Frakturrisiko

25.04.2024 Hypertonie Nachrichten

Beginnen ältere Männer im Pflegeheim eine Antihypertensiva-Therapie, dann ist die Frakturrate in den folgenden 30 Tagen mehr als verdoppelt. Besonders häufig stürzen Demenzkranke und Männer, die erstmals Blutdrucksenker nehmen. Dafür spricht eine Analyse unter US-Veteranen.

Ärztliche Empathie hilft gegen Rückenschmerzen

23.04.2024 Leitsymptom Rückenschmerzen Nachrichten

Personen mit chronischen Rückenschmerzen, die von einfühlsamen Ärzten und Ärztinnen betreut werden, berichten über weniger Beschwerden und eine bessere Lebensqualität.

Update Orthopädie und Unfallchirurgie

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.