Abstract
Purpose
The aim of this study was to investigate the in vitro effect of different concentrations of blood on the morphological and biochemical properties of engineered cartilage. Previous studies have demonstrated a negative effect of blood on native cartilage; however, the effect of the contact of blood on engineered cartilage is unclear.
Methods
Articular chondrocytes were isolated from swine joints, expanded in monolayer culture, and seeded onto collagen membranes. The seeded membranes were cultured for 3 days in the presence of different concentrations of peripheral blood. Some samples were retrieved at the end of the blood contact, others after 21 additional days of standard culture conditions, in order to investigate the “long-term effect” of the blood contact.
Results
All seeded samples showed an increase in the weight and an evident cartilage-like matrix production. A concentration-dependent reduction in the mitochondrial activity due to blood contact was shown at the earlier culture time, followed by a partial recover at the longer culture time.
Conclusion
A blood contact of 3 days affected the chondrocytes’ activity and determined a delay in the maturation of the engineered cartilage. These findings have clinical relevance, as autologous chondrocytes seeded onto biological scaffolds has become an established surgical method for articular cartilage repair. Therefore, further investigation into material sciences should be encouraged for the development of scaffold protecting the reparative cells from the blood insult.
Similar content being viewed by others
References
Aigner J, Tegeler J, Hutzler P, Campoccia D, Pavesio A, Hammer C, Kastenbauer E, Naumann A (1998) Cartilage tissue engineering with novel nonwoven structured biomaterial based on hyaluronic acid benzyl ester. J Biomed Mater Res 42:172–181
Brittberg M, Lindahl A, Nilsson A, Ohlsson C, Isaksson O, Peterson L (1994) Treatment of deep cartilage defects in the knee with autologous chondrocyte transplantation. N Engl J Med 331:889–895
Brittberg M, Peterson L, Sjogren-Jansson E et al (2003) Articular cartilage engineering with autologous chondrocyte transplantation. A review of recent developments. J Bone Joint Surg Am 85-A(Suppl 3):109–115
Cherubino P, Grassi FA, Bulgheroni P, Ronga M (2003) Autologous chondrocyte implantation using a bilayer collagen membrane: a preliminary report. J Orthop Surg (Hong Kong) 11:10–15
Crawford DC, Heveran CM, Cannon WD Jr, Foo LF, Potter HG (2009) An autologous cartilage tissue implant NeoCart for treatment of grade III chondral injury to the distal femur: prospective clinical safety trial at 2 years. Am J Sports Med 37:1334–1343
Ehlers EM, Fuss M, Rohwedel J, Russlies M, Kühnel W, Behrens P (1999) Development of a biocomposite to fill out articular cartilage lesions. Light, scanning and transmission electron microscopy of sheep chondrocytes cultured on a collagen I/III sponge. Ann Anat 181:513–518
Erggelet C, Sittinger M, Lahm A (2003) The arthroscopic implantation of autologous chondrocytes for the treatment of full-thickness cartilage defects of the knee joint. Arthroscopy 19:108–110
Facchini A, Lisignoli G, Cristino S, Roseti L, De Franceschi L, Marconi E, Grigolo B (2006) Human chondrocytes and mesenchymal stem cells grown onto engineered scaffold. Biorheology 43:471–480
Ferruzzi A, Buda R, Faldini C et al (2008) Autologous chondrocytes implantation in the knee joint; open compared with arthroscopic technique. Comparison at a minimum follow-up of five years. J Bone Joint Surg Am 90(suppl 4):90–101
Gerlier D, Thomasset N (1986) Use of MTT colorimetric assay to measure cell activation. J Immunol Methods 94:57–63
Gigante A, Bevilacqua C, Ricevuto A, Mattioli-Belmonte M, Greco F (2007) Membrane-seeded autologous chondrocytes: cell viability and characterization at surgery. Knee Surg Sports Traumatol Arthrosc 15:88–92
Gobbi A, Kon E, Berruto M, Filardo G, Delcogliano M, Boldrini L, Bathan L, Marcacci M (2009) Patellofemoral full-thickness chondral defects treated with second-generation autologous chondrocyte implantation: results at 5 years’ follow-up. Am J Sports Med 37:1083–1092
Grigolo B, Lisignoli G, Piacentini A, Fiorini M, Gobbi P, Mazzotti G, Duca M, Pavesio A, Facchini A (2002) Evidence for redifferentiation of human chondrocytes grown on a hyaluronan-based biomaterial (HYAff 11): molecular, immunohistochemical and ultrastructural analysis. Biomaterials 23:1187–1195
Hooiveld M, Roosendaal G, Wenting M, van den Berg M, Bijlsma J, Lafeber F (2003) Short-term exposure of cartilage to blood results in chondrocyte apoptosis. Am J Pathol 162:943–951
Hooiveld M, Roosendaal G, Vianen ME, van den Berg HM, Bijlsma JW, Lafeber FP (2003) Blood-induced joint damage: longterm effects in vitro and in vivo. J Rheumatol 30:339–344
Hooiveld MJ, Roosendaal G, Vianen ME, van den Berg HM, Bijlsma JW, Lafeber FP (2003) Immature articular cartilage is more susceptible to blood-induced damage than mature articular cartilage: an in vivo animal study. Arthritis Rheum 48:396–403
Hunzinker EB (2002) Articular cartilage repair: basic science and clinical progress. A review of the current status and prospects. Osteoarthr Cartil 10:432–463
Jansen NWD, Roosendal G, Bijlsma JWJ, DeGroot J, Lafeber F (2007) Exposure of human cartilage tissue to low concentrations of blood for a short period of time leads to prolonged cartilage damage. Arthritis Rheum 56:199–207
Jansen NW, Roosendaal G, Lafeber FP (2008) Understanding haemophilic arthropathy: an exploration of current open issues. Br J Haematol 143:632–640
Jansen NW, Roosendaal G, Wenting MJ, Bijlsma JW, Theobald M, Hazewinkel HA, Lafeber FP (2009) Very rapid clearance after a joint bleed in the canine knee cannot prevent adverse effects on cartilage and synovial tissue. Osteoarthr Cartil 7:433–440
Johnson LL (1986) Arthroscopic abrasion arthroplasty. Historical and pathologic perspective: present status. Arthroscopy 2:54–69
Kim MK, Choi SW, Kim SR, Oh IS, Won MH (2010) Autologous chondrocyte implantation in the knee using fibrin. Knee Surg Sports Traumatol Arthrosc 18:528–534
Kreuz PC, Muller S, Ossendorf C et al (2009) Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocytes grafts: four-year clinical results. Arthritis Res Ther 11: R33 (5 March 2009)
Lima EG, Tan AR, Tai T, Bian L, Stoker AM, Ateshian GA, Cook JL, Hung CT (2008) Differences in interleukin-1 response between engineered and native cartilage. Tissue Eng Part A 14:1721–1730
Marcacci M, Berruto M, Brocchetta D, Delcogliano A, Ghinelli D, Gobbi A, Kon E, Pederzini L, Rosa D, Sacchetti GL, Stefani G, Zanasi S (2005) Articular cartilage engineering with Hyalograft® C: 3-year clinical results. Clin Orthop Relat Res 435:96–105
Muirden KD, Peace G, Rogers K (1969) Clearance of Fe59-labelled erythrocytes from normal and inflamed rabbit knee joints: II. Autoradiographic and histological studies. Ann Rheum Dis 28:630–636
Muirden KD (1969) Clearance of Fe59-labelled erythrocytes from normal and inflamed rabbit knee joints. Relationship to the anaemia of rheumatoid arthritis. Ann Rheum Dis 28:548–551
Nehrer S, Domayer S, Dorotka R, Schatz K, Bindreiter U, Kotz R (2006) 3-year clinical outcome after chondrocyte transplantation using a hyaluronan matrix for cartilage repair. Eur J Radiol 57:3–8
Peretti GM, Xu JW, Bonassar LJ, Kirchhoff CH, Yaremchuk MJ, Randolph MA (2006) Review of injectable cartilage engineering using fibrin gel in mice and swine models. Tissue Eng 12:1151–1168
Peretti GM, Buragas MS, Scotti C, Mangiavini L, Sosio C, Di Giancamillo A, Domeneghini C, Fraschini G (2006) An in vitro tissue engineered model for osteochondral repair. Sport Sci Health 1:153–157
Peterson L, Minas T, Brittberg M, Nilsson A, Sjogren-Jansson E, Lindahl A (2000) Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 374:212–234
Pridie KH (1959) A method of resurfacing osteoarthritic joints. J Bone Joint Surg (Br) 41:618–619
Rodriguez-Merchan EC (1997) Pathogenesis, early diagnosis, and prophylaxis for chronic hemophilic synovitis. Clin Orthop Relat Res 343:6–11
Roosendaal G, Vianen ME, van den Berg HM, Lafeber FP, Bijlsma JW (1997) Cartilage damage as a result of hemartrosis in a human in vitro model. J Rheumatol 24:1350–1354
Roosendaal G, Vianen ME, Marx JJ, van den Berg HM, Lafeber FP, Bijlsma JW (1999) Blood-induced joint damage: a human in vitro study. Arthritis Rheum 42:1025–1032
Roosendaal G, Lafeber FP (2003) Blood-induced joint damage in hemophilia. Semin Thromb Hemost 29:37–42
Selmi TA, Verdonk P, Chambat P, Dubrana F, Potel JF, Barnouin L, Neyret P (2008) Autologous chondrocyte implantation in a novel alginate agarose hydrogel: outcome at two years. J Bone Joint Surgery Br 90:597–604
Sittinger M, Reitzel D, Dauner M, Hierlemann H, Hammer C, Kastenbauer E, Planck H, Burmester GR, Bujia J (1996) Resorbable polyesters in cartilage engineering: affinity and biocompatibility of polymer fiber structures to chondrocytes. J Biomed Mater Res 33:57–63
Sosio C, Boschetti F, Bevilacqua C, Mangiavini L, Scotti C, Buragas MS, Biressi S, Fraschini G, Gigante A, Peretti GM (2007) Effect of blood on the morphological, biochemical and biomechanical properties of engineered cartilage. Knee Surg Sports Traumatol Arthrosc 15:1251–1257
Steadman JR, Rodkey WG, Briggs KK, Rodrigo JJ (1999) The microfracture technic in the management of complete cartilage defects in the knee joint. Orthopade 28:26–32
Tajima T, Yoshida E, Yamashita A, Ohmura S, Tomitaka Y, Sugiki M, Asada Y, Maruyama M (2005) Hemoglobin stimulates the expression of matrix metalloproteinases, MMP-2 and MMP-9 by synovial cells: a possible cause of joint damage after intra-articular hemorrhage. J Orthop Res 23:891–898
Wang Y, Blasioli DJ, Kim HJ, Kim HS, Kaplan DL (2006) Cartilage tissue engineering with silk scaffolds and human articular chondrocytes. Biomaterials 27:4434–4442
Acknowledgments
This work was done at the Stem Cell Research Institute (SCRI) directed by Professor Giulio Cossu. The authors gratefully acknowledge the Società Italiana Ginocchio Artroscopia Sport Cartilagine e Tecnologie Ortopediche (SIGASCOT; ex SICG), which supported this work and Dr. Claudia Bevilacqua for her precious assistant in the experiment analysis. A special thank is given to the Spaccio Agricolo Agripig and to Dr. Antonio Sorice for their assistance in animal management.
Conflict of interest
None of the Authors have actual or potential conflict of interest in connection with the work presented in the submitted manuscript. No competing financial interests exist.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Sosio, C., Boschetti, F., Mangiavini, L. et al. Blood exposure has a negative effect on engineered cartilage. Knee Surg Sports Traumatol Arthrosc 19, 1035–1042 (2011). https://doi.org/10.1007/s00167-010-1296-9
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00167-010-1296-9