The Use of Scaffolds in the Treatment of Osteochondral Lesions in the Knee: Current Concepts and Future Trends

Abstract

Long after the first reports on human autologous chondrocyte implantation (ACI) by Brittberg in 1994, the development of a so-called optimal technology for osteochondral tissue regeneration is still one of the most challenging issues in knee surgery. Although the short- and intermediate-term results of ACI appear to be favorable, resources are being directed toward scaffold research to improve the technology. Scaffolds used for osteochondral repair may be either cell or noncell-based before its implantation in the knee. The characteristics that make scaffolds optimal for clinical use are that they be biocompatible, biodegradable, permeable, reproducible, mechanically stable, noncytotoxic, and capable of serving as a temporary support for the cells while allowing for eventual replacement by matrix components synthesized by the implanted cells. There is a growing interest in noncell and last-minute cell seeding technologies since they allow for a one-step surgery eliminating the morbidity and necessity of a previous chondral biopsy. Although clinical and histological results from many, already clinically available scaffolds seem to be promising, improvements throughout these technologies and the developments of new ones are still necessary to obtain a more efficient biological response as well as to improve the implant's stability. Moreover, as the understanding of interactions between articular cartilage and subchondral bone continues to evolve, increased attention should be directed at treatment options for the entire osteochondral unit, rather than focusing on the articular surface only.

Keywords

cartilage - scaffolds - repair - knee

• References

• 1 Kim HK, Moran ME, Salter RB. The potential for regeneration of articular cartilage in defects created by chondral shaving and subchondral abrasion. An experimental investigation in rabbits. J Bone Joint Surg Am 1991; 73 (9) 1301-1315
• 2 Safran MR, Kim H, Zaffagnini S. The use of scaffolds in the management of articular cartilage injury. J Am Acad Orthop Surg 2008; 16 (6) 306-311
• 3 Cerynik DL, Lewullis GE, Joves BC, Palmer MP, Tom JA. Outcomes of microfracture in professional basketball players. Knee Surg Sports Traumatol Arthrosc 2009; 17 (9) 1135-1139
• 4 Dorotka R, Windberger U, Macfelda K, Bindreiter U, Toma C, Nehrer S. Repair of articular cartilage defects treated by microfracture and a three-dimensional collagen matrix. Biomaterials 2005; 26 (17) 3617-3629
• 5 Steadman JR, Rodkey WG, Singleton SB , et al. Microfracture technique for full-thickness chondral defects: technique and clinical results. Oper Tech Orthop 1997; 7: 300-304
• 6 Minas T. Chondrocyte implantation in the repair of chondral lesions of the knee: economics and quality of life. Am J Orthop 1998; 27 (11) 739-744
• 7 Brittberg M, Lindahl 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 (14) 889-895
• 8 Peterson L, Minas T, Brittberg M, Nilsson A, Sjögren-Jansson E, Lindahl A. Two- to 9-year outcome after autologous chondrocyte transplantation of the knee. Clin Orthop Relat Res 2000; 374 (374) 212-234
• 9 Benya PD, Shaffer JD. Dedifferentiated chondrocytes reexpress the differentiated collagen phenotype when cultured in agarose gels. Cell 1982; 30 (1) 215-224
• 10 Gomoll AH, Madry H, Knutsen G , et al. The subchondral bone in articular cartilage repair: current problems in the surgical management. Knee Surg Sports Traumatol Arthrosc 2010; 18 (4) 434-447
• 11 Verdonk PCM, Forsyth RG, Wang J , et al. Characterisation of human knee meniscus cell phenotype. Osteoarthritis Cartilage 2005; 13 (7) 548-560
• 12 Stella JA, D'Amore A, Wagner WR, Sacks MS. On the biomechanical function of scaffolds for engineering load-bearing soft tissues. Acta Biomater 2010; 6 (7) 2365-2381
• 13 Bonaventure J, Kadhom N, Cohen-Solal L , et al. Reexpression of cartilage-specific genes by dedifferentiated human articular chondrocytes cultured in alginate beads. Exp Cell Res 1994; 212 (1) 97-104
• 14 Kasemkijwattana C, Hongeng S, Kesprayura S, Rungsinaporn V, Chaipinyo K, Chansiri K. Autologous bone marrow mesenchymal stem cells implantation for cartilage defects: two cases report. J Med Assoc Thai 2011; 94 (3) 395-400
• 15 Homminga GN, Buma P, Koot HWJ, van der Kraan PM, van den Berg WB. Chondrocyte behavior in fibrin glue in vitro. Acta Orthop Scand 1993; 64 (4) 441-445
• 16 Choi NY, Kim BW, Yeo WJ , et al. Gel-type autologous chondrocyte (Chondron) implantation for treatment of articular cartilage defects of the knee. BMC Musculoskelet Disord 2010; 11: 103
• 17 Visna P, Pasa L, Cizmár I, Hart R, Hoch J. Treatment of deep cartilage defects of the knee using autologous chondrograft transplantation and by abrasive techniques—a randomized controlled study. Acta Chir Belg 2004; 104 (6) 709-714
• 18 McCormick F, Yanke A, Provencher MT, Cole BJ. Minced articular cartilage—basic science, surgical technique, and clinical application. Sports Med Arthrosc 2008; 16 (4) 217-220
• 19 McNickle AG, Provencher MT, Cole BJ. Overview of existing cartilage repair technology. Sports Med Arthrosc 2008; 16 (4) 196-201
• 20 Wakitani S, Kimura T, Hirooka A , et al. Repair of rabbit articular surfaces with allograft chondrocytes embedded in collagen gel. J Bone Joint Surg Br 1989; 71 (1) 74-80
• 21 Kawamura S, Wakitani S, Kimura T , et al. Articular cartilage repair. Rabbit experiments with a collagen gel-biomatrix and chondrocytes cultured in it. Acta Orthop Scand 1998; 69 (1) 56-62
• 22 Cascio BM, Sharma B. The future of cartilage repair. Oper Tech Sport Med 2008; 16: 221-224
• 23 Ochi M, Uchio Y, Kawasaki K, Wakitani S, Iwasa J. Transplantation of cartilage-like tissue made by tissue engineering in the treatment of cartilage defects of the knee. J Bone Joint Surg Br 2002; 84 (4) 571-578
• 24 Tohyama H, Yasuda K, Minami A , et al. Atelocollagen-associated autologous chondrocyte implantation for the repair of chondral defects of the knee: a prospective multicenter clinical trial in Japan. J Orthop Sci 2009; 14 (5) 579-588
• 25 Pontz B, Meigel W, Rauterberg J, Kühn K. Localization of two species specific antigenic determinants on the peptide chains of calf skin collagen. Eur J Biochem 1970; 16 (1) 50-54
• 26 Furthmayr H, Timpl R. Immunochemistry of collagens and procollagens. Int Rev Connect Tissue Res 1976; 7: 61-99
• 27 Ochi M, Uchio Y, Matsusaki M, Wakitani S, Sumen Y. Cartilage repair: a new surgical procedure of cultured chondrocyte transplantation. In: Chan KM, Fu F, Maffuli N, Rolf C, Kurosaka M, Liu S, eds. Controversies in orthopedic sport medicine. Hong Kong: Williams & Wilkins Asia-Pacific Ltd; 1998: 549-63
• 28 Uchio Y, Ochi M, Matsusaki M, Kurioka H, Katsube K. Human chondrocyte proliferation and matrix synthesis cultured in Atelocollagen gel. J Biomed Mater Res 2000; 50 (2) 138-143
• 29 Katsube K, Ochi M, Uchio Y , et al. Repair of articular cartilage defects with cultured chondrocytes in Atelocollagen gel. Comparison with cultured chondrocytes in suspension. Arch Orthop Trauma Surg 2000; 120 (3-4) 121-127
• 30 Badylak SF, Freytes DO, Gilbert TW. Extracellular matrix as a biological scaffold material: Structure and function. Acta Biomater 2009; 5 (1) 1-13
• 31 Hu X, Yao L, Lu C, Wang S, Chen Y. Experimental and clinical investigations of human insoluble bone matrix gelatin. A report of 24 cases. Clin Orthop Relat Res 1993; 293 (293) 360-365
• 32 Iwata H, Sakano S, Itoh T, Bauer TW. Demineralized bone matrix and native bone morphogenetic protein in orthopaedic surgery. Clin Orthop Relat Res 2002; 395 (395) 99-109
• 33 Nogami H, Oohira A, Terashima Y, Urist MR. Ultrastructure of chondrogenetic interactions between bone matrix gelatin and mesenchymal cells. Clin Orthop Relat Res 1978; 133 (133) 238-245
• 34 Mizutani H, Urist MR. The nature of bone morphogenetic protein (BMP) fractions derived from bovine bone matrix gelatin. Clin Orthop Relat Res 1982; 171 (171) 213-223
• 35 Dahlberg L, Kreicbergs A. Demineralized allogeneic bone matrix for cartilage repair. J Orthop Res 1991; 9 (1) 11-19
• 36 Yang B, Yin Z, Cao J , et al. In vitro cartilage tissue engineering using cancellous bone matrix gelatin as a biodegradable scaffold. Biomed Mater 2010; 5 (4) 045003
• 37 Rahfoth B, Weisser J, Sternkopf F, Aigner T, von der Mark K, Bräuer R. Transplantation of allograft chondrocytes embedded in agarose gel into cartilage defects of rabbits. Osteoarthritis Cartilage 1998; 6 (1) 50-65
• 38 Freed LE, Marquis JC, Nohria A, Emmanual J, Mikos AG, Langer R. Neocartilage formation in vitro and in vivo using cells cultured on synthetic biodegradable polymers. J Biomed Mater Res 1993; 27 (1) 11-23
• 39 Freed LE, Hollander AP, Martin I, Barry JR, Langer R, Vunjak-Novakovic G. Chondrogenesis in a cell-polymer-bioreactor system. Exp Cell Res 1998; 240 (1) 58-65
• 40 Chu CR, Coutts RD, Yoshioka M, Harwood FL, Monosov AZ, Amiel D. Articular cartilage repair using allogeneic perichondrocyte-seeded biodegradable porous polylactic acid (PLA): a tissue-engineering study. J Biomed Mater Res 1995; 29 (9) 1147-1154
• 41 Freed LE, Grande DA, Lingbin Z, Emmanual J, Marquis JC, Langer R. Joint resurfacing using allograft chondrocytes and synthetic biodegradable polymer scaffolds. J Biomed Mater Res 1994; 28 (8) 891-899
• 42 Niederauer GG, Slivka MA, Leatherbury NC , et al. Evaluation of multiphase implants for repair of focal osteochondral defects in goats. Biomaterials 2000; 21 (24) 2561-2574
• 43 Rotter N, Aigner J, Naumann A , et al. Cartilage reconstruction in head and neck surgery: comparison of resorbable polymer scaffolds for tissue engineering of human septal cartilage. J Biomed Mater Res 1998; 42 (3) 347-356
• 44 Marcacci M, Berruto M, Brocchetta D , et al. Articular cartilage engineering with Hyalograft C: 3-year clinical results. Clin Orthop Relat Res 2005; 435 (435) 96-105
• 45 Grigolo B, Roseti L, Fiorini M , et al. Transplantation of chondrocytes seeded on a hyaluronan derivative (hyaff-11) into cartilage defects in rabbits. Biomaterials 2001; 22 (17) 2417-2424
• 46 Almqvist KF, Wang L, Broddelez C, Veys EM, Verbruggen G. Biological freezing of human articular chondrocytes. Osteoarthritis Cartilage 2001; 9 (4) 341-350
• 47 Almqvist KF, Wang L, Wang J , et al. Culture of chondrocytes in alginate surrounded by fibrin gel: characteristics of the cells over a period of eight weeks. Ann Rheum Dis 2001; 60 (8) 781-790
• 48 Almqvist KF, Dhollander AAM, Verdonk PCM, Forsyth R, Verdonk R, Verbruggen G. Treatment of cartilage defects in the knee using alginate beads containing human mature allogenic chondrocytes. Am J Sports Med 2009; 37 (10) 1920-1929
• 49 Dhollander AAM, Huysse WCJ, Verdonk PC , et al. MRI evaluation of a new scaffold-based allogenic chondrocyte implantation for cartilage repair. Eur J Radiol 2010; 75 (1) 72-81
• 50 Di Martino A, Sittinger M, Risbud MV. Chitosan: a versatile biopolymer for orthopaedic tissue-engineering. Biomaterials 2005; 26 (30) 5983-5990
• 51 Lahiji A, Sohrabi A, Hungerford DS, Frondoza CG. Chitosan supports the expression of extracellular matrix proteins in human osteoblasts and chondrocytes. J Biomed Mater Res 2000; 51 (4) 586-595
• 52 Hoemann CD, Sun J, Légaré A, McKee MD, Buschmann MD. Tissue engineering of cartilage using an injectable and adhesive chitosan-based cell-delivery vehicle. Osteoarthritis Cartilage 2005; 13 (4) 318-329
• 53 Li Z, Zhang M. Chitosan-alginate as scaffolding material for cartilage tissue engineering. J Biomed Mater Res A 2005; 75 (2) 485-493
• 54 van Susante JL, Buma P, Homminga GN, van den Berg WB, Veth RP. Chondrocyte-seeded hydroxyapatite for repair of large articular cartilage defects. A pilot study in the goat. Biomaterials 1998; 19 (24) 2367-2374
• 55 Barker TH, Fuller GM, Klinger MM, Feldman DS, Hagood JS. Modification of fibrinogen with poly(ethylene glycol) and its effects on fibrin clot characteristics. J Biomed Mater Res 2001; 56 (4) 529-535
• 56 Bryant SJ, Bender RJ, Durand KL, Anseth KS. Encapsulating chondrocytes in degrading PEG hydrogels with high modulus: engineering gel structural changes to facilitate cartilaginous tissue production. Biotechnol Bioeng 2004; 86 (7) 747-755
• 57 Kon E, Delcogliano M, Filardo G, Busacca M, Di Martino A, Marcacci M. Novel nano-composite multilayered biomaterial for osteochondral regeneration: a pilot clinical trial. Am J Sports Med 2011; 39 (6) 1180-1190
• 58 Kon E, Delcogliano M, Filardo G , et al. Orderly osteochondral regeneration in a sheep model using a novel nano-composite multilayered biomaterial. J Orthop Res 2010; 28 (1) 116-124
• 59 Kon E, Mutini A, Arcangeli E , et al. Novel nanostructured scaffold for osteochondral regeneration: pilot study in horses. J Tissue Eng Regen Med 2010; 4 (4) 300-308
• 60 Tampieri A, Sandri M, Landi E , et al. Design of graded biomimetic osteochondral composite scaffolds. Biomaterials 2008; 29 (26) 3539-3546
• 61 Kerker JT, Leo AJ, Sgaglione NA. Cartilage repair: synthetics and scaffolds: basic science, surgical techniques, and clinical outcomes. Sports Med Arthrosc 2008; 16 (4) 208-216
• 62 Saithna AA, Carey-Smith R, Dhillon M, Thompson P, Spalding T. Synthetic polymer scaffolds for repair of small articular cartilage defects of the knee: Early clinical and radiological results. Presented at the British Orthopaedic Association Conference, Liverpool, England, September 2008.
• 63 Davidson PA, Rivenburgh DW. Prospective evaluation of osteochondral defects in the knee treated with biodegradable scaffolds (SS-45). Presented at the Arthroscopic Association of North America Meeting, Denver, Colorado, 2007.
• 64 Chen G, Sato T, Ushida T , et al. The use of a novel PLGA fiber/collagen composite web as a scaffold for engineering of articular cartilage tissue with adjustable thickness. J Biomed Mater Res A 2003; 67 (4) 1170-1180
• 65 Chen G, Sato T, Ushida T, Ochiai N, Tateishi T. Tissue engineering of cartilage using a hybrid scaffold of synthetic polymer and collagen. Tissue Eng 2004; 10 (3-4) 323-330
• 66 Iwasa J, Engebretsen L, Shima Y, Ochi M. Clinical application of scaffolds for cartilage tissue engineering. Knee Surg Sports Traumatol Arthrosc 2009; 17 (6) 561-577
• 67 Steinwachs MR, Guggi T, Kreuz PC. Marrow stimulation techniques. Injury 2008; 39 (Suppl. 01) S26-S31
• 68 Selmi TA, Verdonk P, Chambat P , et al. Autologous chondrocyte implantation in a novel alginate-agarose hydrogel: outcome at two years. J Bone Joint Surg Br 2008; 90 (5) 597-604
• 69 Patrascu JM, Freymann U, Kaps C, Poenaru DV. Repair of a post-traumatic cartilage defect with a cell-free polymer-based cartilage implant: a follow-up at two years by MRI and histological review. J Bone Joint Surg Br 2010; 92 (8) 1160-1163
• 70 Hegewald AA, Ringe J, Bartel J , et al. Hyaluronic acid and autologous synovial fluid induce chondrogenic differentiation of equine mesenchymal stem cells: a preliminary study. Tissue Cell 2004; 36 (6) 431-438
• 71 Knecht S, Erggelet C, Endres M, Sittinger M, Kaps C, Stüssi E. Mechanical testing of fixation techniques for scaffold-based tissue-engineered grafts. J Biomed Mater Res B Appl Biomater 2007; 83 (1) 50-57
• 72 Zelle S, Zantop T, Schanz S, Petersen W. Arthroscopic techniques for the fixation of a three-dimensional scaffold for autologous chondrocyte transplantation: structural properties in an in vitro model. Arthroscopy 2007; 23 (10) 1073-1078
• 73 Erggelet C, Neumann K, Endres M, Haberstroh K, Sittinger M, Kaps C. Regeneration of ovine articular cartilage defects by cell-free polymer-based implants. Biomaterials 2007; 28 (36) 5570-5580
• 74 Zantop T, Petersen W. Arthroscopic implantation of a matrix to cover large chondral defect during microfracture. Arthroscopy 2009; 25 (11) 1354-1360
• 75 Barker TH, Fuller GM, Klinger MM, Feldman DS, Hagood JS. Modification of fibrinogen with poly(ethylene glycol) and its effects on fibrin clot characteristics. J Biomed Mater Res 2001; 56 (4) 529-535
• 76 Temenoff JS, Athanasiou KA, LeBaron RG, Mikos AG. Effect of poly(ethylene glycol) molecular weight on tensile and swelling properties of oligo(poly(ethylene glycol) fumarate) hydrogels for cartilage tissue engineering. J Biomed Mater Res 2002; 59 (3) 429-437
• 77 Kon E, Delcogliano M, Filardo G, Montaperto C, Marcacci M. Second generation issues in cartilage repair. Sports Med Arthrosc 2008; 16 (4) 221-229
• 78 Erggelet C, Kreuz PC, Mrosek EH , et al. Autologous chondrocyte implantation versus ACI using 3D-bioresorbable graft for the treatment of large full-thickness cartilage lesions of the knee. Arch Orthop Trauma Surg 2010; 130 (8) 957-964
• 79 Kreuz PC, Müller S, Ossendorf C, Kaps C, Erggelet C. Treatment of focal degenerative cartilage defects with polymer-based autologous chondrocyte grafts: four-year clinical results. Arthritis Res Ther 2009; 11 (2) R33
• 80 Ahmed TA, Giulivi A, Griffith M, Hincke M. Fibrin glues in combination with mesenchymal stem cells to develop a tissue-engineered cartilage substitute. Tissue Eng Part A 2011; 17 (3-4) 323-335
• 81 Nguyen LH, Kudva AK, Saxena NS, Roy K. Engineering articular cartilage with spatially-varying matrix composition and mechanical properties from a single stem cell population using a multi-layered hydrogel. Biomaterials 2011; 32 (29) 6946-6952