Skip to main content
Top
Published in: Arthritis Research & Therapy 6/2008

Open Access 01-12-2008 | Research article

Characteristics of repair tissue in second-look and third-look biopsies from patients treated with engineered cartilage: relationship to symptomatology and time after implantation

Authors: Paola Brun, Sally C Dickinson, Barbara Zavan, Roberta Cortivo, Anthony P Hollander, Giovanni Abatangelo

Published in: Arthritis Research & Therapy | Issue 6/2008

Login to get access

Abstract

Introduction

The present study established characteristics of tissue regrowth in patients suffering knee lesions treated with grafts of autologous chondrocytes grown on three-dimensional hyaluronic acid biomaterials.

Methods

This multicentred study involved a second-look arthroscopy/biopsy, 5 to 33 months post implant (n = 63). Seven patients allowed a third-look biopsy, three of which were performed 18 months post implant. Characteristics of tissues were histologically and histochemically evaluated. The remaining bone stubs were evaluated for cartilage/bone integration. For data analysis, biopsies were further divided into those obtained from postoperative symptomatic patients (n = 41) or from asymptomatic patients (n = 22).

Results

The percentage of hyaline regenerated tissues was significantly greater in biopsies obtained after, versus within, 18 months of implantation. Differences were also observed between symptomatic and asymptomatic patients: reparative tissues taken from symptomatic patients 18 months after grafting were mainly fibrocartilage or mixed (hyaline–fibrocartilage) tissue, while tissues taken from asymptomatic patients were hyaline cartilage in 83% of biopsies. In a small group of asymptomatic patients (n = 3), second-look and third-look biopsies taken 18 months after surgery confirmed maturation of the newly formed tissue over time. Cartilage maturation occurred from the inner regions of the graft, in contact with subchondral bone, towards the periphery of the implant.

Conclusions

The study indicates that, in asymptomatic patients after chondrocyte implantation, regenerated tissue undergoes a process of maturation that in the majority of cases takes longer than 18 months for completion and leads to hyaline tissue and not fibrous cartilage. Persistence of symptoms might reflect the presence of a nonhyaline cartilage repair tissue.
Appendix
Available only for authorised users
Literature
1.
go back to reference Caplan AI, Elyaderami M, Mochizuki Y, Wakitini S, Goldberg VM: Principles of cartilage repair and regeneration. Clin Orthop Relat Res. 1997, 342: 254-269. 10.1097/00003086-199709000-00033.CrossRefPubMed Caplan AI, Elyaderami M, Mochizuki Y, Wakitini S, Goldberg VM: Principles of cartilage repair and regeneration. Clin Orthop Relat Res. 1997, 342: 254-269. 10.1097/00003086-199709000-00033.CrossRefPubMed
2.
go back to reference Hunziker EB: Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage. 2002, 10: 432-463. 10.1053/joca.2002.0801.CrossRefPubMed Hunziker EB: Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthritis Cartilage. 2002, 10: 432-463. 10.1053/joca.2002.0801.CrossRefPubMed
3.
go back to reference Minas T, Nehrer S: Current concepts in the treatment of articular cartilage defects. Orthopedics. 1997, 20: 525-538.PubMed Minas T, Nehrer S: Current concepts in the treatment of articular cartilage defects. Orthopedics. 1997, 20: 525-538.PubMed
4.
go back to reference Simon TM, Jackson DW: Articular cartilage: injury pathways and treatment options. Sports Med Arthrosc. 2006, 14: 146-154. 10.1097/00132585-200609000-00006.CrossRefPubMed Simon TM, Jackson DW: Articular cartilage: injury pathways and treatment options. Sports Med Arthrosc. 2006, 14: 146-154. 10.1097/00132585-200609000-00006.CrossRefPubMed
5.
go back to reference Brittberg M, Lindhal A, Nilsson A, Ohlsson C, Isaksson O, Peterson L: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994, 331: 889-895. 10.1056/NEJM199410063311401.CrossRefPubMed Brittberg M, Lindhal A, Nilsson A, Ohlsson C, Isaksson O, Peterson L: Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med. 1994, 331: 889-895. 10.1056/NEJM199410063311401.CrossRefPubMed
6.
go back to reference Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A: Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop. 2000, 374: 212-234. 10.1097/00003086-200005000-00020.CrossRefPubMed Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A: Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop. 2000, 374: 212-234. 10.1097/00003086-200005000-00020.CrossRefPubMed
7.
go back to reference Richardson JB, Caterson B, Evans EH, Ashton BA, Roberts S: Repair of human articular cartilage after implantation of autologous chondrocytes. J Bone Joint Surg Br. 1999, 81: 1064-1068. 10.1302/0301-620X.81B6.9343.CrossRefPubMed Richardson JB, Caterson B, Evans EH, Ashton BA, Roberts S: Repair of human articular cartilage after implantation of autologous chondrocytes. J Bone Joint Surg Br. 1999, 81: 1064-1068. 10.1302/0301-620X.81B6.9343.CrossRefPubMed
8.
go back to reference Wasiak J, Clar C, Villanueva E: Autologous cartilage implantation for full thickness articular cartilage defects of the knee. Cochrane Database Syst Rev. 2006, 3: CD003323-PubMed Wasiak J, Clar C, Villanueva E: Autologous cartilage implantation for full thickness articular cartilage defects of the knee. Cochrane Database Syst Rev. 2006, 3: CD003323-PubMed
9.
go back to reference Campoccia D, Doherty P, Radice M, Brun P, Abatangelo G, Williams DF: Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials. 1998, 19: 2101-2127. 10.1016/S0142-9612(98)00042-8.CrossRefPubMed Campoccia D, Doherty P, Radice M, Brun P, Abatangelo G, Williams DF: Semisynthetic resorbable materials from hyaluronan esterification. Biomaterials. 1998, 19: 2101-2127. 10.1016/S0142-9612(98)00042-8.CrossRefPubMed
10.
go back to reference Aigner J, Tegeler J, Hutzler P, Campoccia D, Pavesio A, Hammer C, Kastenbauer E, Naumann A: Cartilage tissue engineering with novel non-woven structured biomaterial based on hyaluronic acid benzyl ester. J Biomed Mater Res. 1998, 42: 172-181. 10.1002/(SICI)1097-4636(199811)42:2<172::AID-JBM2>3.0.CO;2-M.CrossRefPubMed Aigner J, Tegeler J, Hutzler P, Campoccia D, Pavesio A, Hammer C, Kastenbauer E, Naumann A: Cartilage tissue engineering with novel non-woven structured biomaterial based on hyaluronic acid benzyl ester. J Biomed Mater Res. 1998, 42: 172-181. 10.1002/(SICI)1097-4636(199811)42:2<172::AID-JBM2>3.0.CO;2-M.CrossRefPubMed
11.
go back to reference Brun P, Abatangelo G, Radice M, Zacchi V, Guidolin D, Daga Gordini D, Cortivo R: Chondrocyte aggregation and reorganization into three-dimentional scaffolds. J Biomed Mater Res. 1999, 46: 337-346. 10.1002/(SICI)1097-4636(19990905)46:3<337::AID-JBM5>3.0.CO;2-Q.CrossRefPubMed Brun P, Abatangelo G, Radice M, Zacchi V, Guidolin D, Daga Gordini D, Cortivo R: Chondrocyte aggregation and reorganization into three-dimentional scaffolds. J Biomed Mater Res. 1999, 46: 337-346. 10.1002/(SICI)1097-4636(19990905)46:3<337::AID-JBM5>3.0.CO;2-Q.CrossRefPubMed
12.
go back to reference Radice M, Brun P, Cortivo R, Scapinelli R, Bataillard C, Abatangelo G: Hyaluronan-based biopolymers as delivery vehicles for bone-marrow-derived mesenchymal progenitors. J Biomed Mater Res. 2000, 50: 101-109. 10.1002/(SICI)1097-4636(200005)50:2<101::AID-JBM2>3.0.CO;2-M.CrossRefPubMed Radice M, Brun P, Cortivo R, Scapinelli R, Bataillard C, Abatangelo G: Hyaluronan-based biopolymers as delivery vehicles for bone-marrow-derived mesenchymal progenitors. J Biomed Mater Res. 2000, 50: 101-109. 10.1002/(SICI)1097-4636(200005)50:2<101::AID-JBM2>3.0.CO;2-M.CrossRefPubMed
13.
go back to reference Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G, Duca M, Pavesio A, Facchini A: Evidence for re-differentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAFF-11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials. 2002, 23: 1187-1195. 10.1016/S0142-9612(01)00236-8.CrossRefPubMed Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G, Duca M, Pavesio A, Facchini A: Evidence for re-differentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAFF-11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials. 2002, 23: 1187-1195. 10.1016/S0142-9612(01)00236-8.CrossRefPubMed
14.
go back to reference Girotto D, Urbani S, Brun P, Renier D, Barbucci R, Abatangelo G: Tissue-specific gene expression in chondrocytes grown on three-dimensional hyaluronic acid scaffolds. Biomaterials. 2003, 24: 3265-3275. 10.1016/S0142-9612(03)00160-1.CrossRefPubMed Girotto D, Urbani S, Brun P, Renier D, Barbucci R, Abatangelo G: Tissue-specific gene expression in chondrocytes grown on three-dimensional hyaluronic acid scaffolds. Biomaterials. 2003, 24: 3265-3275. 10.1016/S0142-9612(03)00160-1.CrossRefPubMed
15.
go back to reference Pavesio A, Abatangelo G, Torrione A, Brocchetta D, Hollander A, Kon E, Torasso F, Zanasi S, Marcacci M: Hyaluronan-based scaffolds (hyalograftC) in the treatment of knee cartilage defects: preliminary clinical findings. Novartis Found Symp. 2003, 249: 73-83. Pavesio A, Abatangelo G, Torrione A, Brocchetta D, Hollander A, Kon E, Torasso F, Zanasi S, Marcacci M: Hyaluronan-based scaffolds (hyalograftC) in the treatment of knee cartilage defects: preliminary clinical findings. Novartis Found Symp. 2003, 249: 73-83.
16.
go back to reference Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzin L, Rosa D, Sacchetti GL, Stefani G, Zanasi S: Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res. 2005, 435: 96-105. 10.1097/01.blo.0000165737.87628.5b.CrossRefPubMed Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzin L, Rosa D, Sacchetti GL, Stefani G, Zanasi S: Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res. 2005, 435: 96-105. 10.1097/01.blo.0000165737.87628.5b.CrossRefPubMed
17.
go back to reference Dickinson SC, Sims TJ, Pittarello L, Soranzo C, Pavesio A, Hollander AP: Quantitative outcome measures of cartilage repair in patients treated by tissue engineering. Tissue Eng. 2005, 11: 277-287. 10.1089/ten.2005.11.277.CrossRefPubMed Dickinson SC, Sims TJ, Pittarello L, Soranzo C, Pavesio A, Hollander AP: Quantitative outcome measures of cartilage repair in patients treated by tissue engineering. Tissue Eng. 2005, 11: 277-287. 10.1089/ten.2005.11.277.CrossRefPubMed
18.
go back to reference Hollander AP, Dickinson SC, Sims TJ, Brun P, Cortivo R, Kon E, Marcacci M, Zanasi S, Borrione A, De Luca C, Pavesio A, Soranzo C, Abtangelo G: Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees. Tissue Eng. 2006, 12: 1787-1798. 10.1089/ten.2006.12.1787.CrossRefPubMed Hollander AP, Dickinson SC, Sims TJ, Brun P, Cortivo R, Kon E, Marcacci M, Zanasi S, Borrione A, De Luca C, Pavesio A, Soranzo C, Abtangelo G: Maturation of tissue engineered cartilage implanted in injured and osteoarthritic human knees. Tissue Eng. 2006, 12: 1787-1798. 10.1089/ten.2006.12.1787.CrossRefPubMed
19.
go back to reference Sandell LJ, Morris N, Robbins JR, Goldring M: Alternatively spliced type II procollagen mRNAs define distinct populations of cells during vertebral development: differential expression of the amino-propeptide. J Cell Biol. 1991, 114: 1307-1319. 10.1083/jcb.114.6.1307.CrossRefPubMed Sandell LJ, Morris N, Robbins JR, Goldring M: Alternatively spliced type II procollagen mRNAs define distinct populations of cells during vertebral development: differential expression of the amino-propeptide. J Cell Biol. 1991, 114: 1307-1319. 10.1083/jcb.114.6.1307.CrossRefPubMed
20.
go back to reference Tognana E, Chen F, Padera RF, Leddy HA, Christensen SE, Guilak F, Vujak-Novakocic G, Freed LE: Adjacent tissues (cartilage, bone) affect the functional integration of engineered calf cartilage in vitro. Osteoarthritis Cartilage. 2005, 13: 129-138. 10.1016/j.joca.2004.10.015.CrossRefPubMed Tognana E, Chen F, Padera RF, Leddy HA, Christensen SE, Guilak F, Vujak-Novakocic G, Freed LE: Adjacent tissues (cartilage, bone) affect the functional integration of engineered calf cartilage in vitro. Osteoarthritis Cartilage. 2005, 13: 129-138. 10.1016/j.joca.2004.10.015.CrossRefPubMed
21.
go back to reference Brun P, Panfilo S, Daga Gordini D, Cortivo R, Abatangelo G: The effect of hyaluronan on CD44-mediated proliferation of normal and hydroxyl radical-damaged chondrocytes. Osteoarthritis Cartilage. 2003, 11: 208-216. 10.1016/S1063-4584(02)00352-7.CrossRefPubMed Brun P, Panfilo S, Daga Gordini D, Cortivo R, Abatangelo G: The effect of hyaluronan on CD44-mediated proliferation of normal and hydroxyl radical-damaged chondrocytes. Osteoarthritis Cartilage. 2003, 11: 208-216. 10.1016/S1063-4584(02)00352-7.CrossRefPubMed
22.
go back to reference Kujawa MJ, Caplan AI: Hyaluronic acid bonded to cell-surface stimulates chondrogenesis in stage 24 limb mesenchyme cell cultures. Dev Biol. 1986, 114: 504-518. 10.1016/0012-1606(86)90214-9.CrossRefPubMed Kujawa MJ, Caplan AI: Hyaluronic acid bonded to cell-surface stimulates chondrogenesis in stage 24 limb mesenchyme cell cultures. Dev Biol. 1986, 114: 504-518. 10.1016/0012-1606(86)90214-9.CrossRefPubMed
23.
go back to reference Toole BP: Hyaluronan in morphogenesis. J Intern Med. 1997, 242: 35-40. 10.1046/j.1365-2796.1997.00171.x.CrossRefPubMed Toole BP: Hyaluronan in morphogenesis. J Intern Med. 1997, 242: 35-40. 10.1046/j.1365-2796.1997.00171.x.CrossRefPubMed
Metadata
Title
Characteristics of repair tissue in second-look and third-look biopsies from patients treated with engineered cartilage: relationship to symptomatology and time after implantation
Authors
Paola Brun
Sally C Dickinson
Barbara Zavan
Roberta Cortivo
Anthony P Hollander
Giovanni Abatangelo
Publication date
01-12-2008
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 6/2008
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/ar2549

Other articles of this Issue 6/2008

Arthritis Research & Therapy 6/2008 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.