Abstract
Osteochondral (OC) defect repair is a significant clinical challenge. Osteoarthritis results in articular cartilage/subchondral bone tissue degeneration and tissue loss, which in the long run results in cartilage/ostecochondral defect formation. OC defects are commonly approached with autografts and allografts, and both these options have found limitations. Alternatively, tissue engineered strategies with biodegradable scaffolds with and without cells and growth factors have been developed. In order to approach regeneration of complex tissues such as osteochondral, advanced tissue engineered grafts including biphasic, triphasic, and gradient configurations are considered. The graft design is motivated to promote cartilage and bone layer formation with an interdigitating transitional zone (i.e., bone–cartilage interface). Some of the engineered OC grafts with autologous cells have shown promise for OC defect repair and a few of them have advanced into clinical trials. This chapter presents synthetic osteochondral designs and the progress that has been made in terms of the clinical translation.
Keywords
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Murphy L, Helmick CG (2012) The impact of osteoarthritis in the United States: a population-health perspective. Orthop Nurs 31(2):85–91
Pappas AM (1981) Osteochondrosis dissecans. Clin Orthop 158:59–69
Nukavarapu SP, Dorcemus DL (2013) Osteochondral tissue engineering: current strategies and challenges. Biotechnol Adv 31(5):706–721
Athanasiou KA, Zhu CF, Wang X, Agrawal CM (2000) Effects of aging and dietary restriction on the structural integrity of rat articular cartilage. Ann Biomed Eng 28(2):143–149
Martin I, Miot S, Barbero A, Jakob M, Wendt D (2007) Osteochondral tissue engineering. J Biomech 40(4):750–765
Fazzalari NL (2008) Bone remodeling: a review of the bone microenvironment perspective for fragility fracture (osteoporosis) of the hip. Semin Cell Dev Biol 19(5):467–472
Brandt KD, Dieppe P, Radin EL (2008) Etiopathogenesis of osteoarthritis. Rheum Dis Clin North Am 34(3):531–559
Dorcemus DL, George EO, Dealy CN, Nukavarapu SP (2017) Harnessing external cues: development and evaluation of an in vitro culture system for osteochondral tissue engineering. Tissue Eng Part A 23(15–16):719–737
Nukavarapu S, Freeman J, Laurencin C (2015) Regenerative engineering of musculoskeletal tissues and interfaces. Elsevier Science & Technology, Amsterdam
Amini AR, Laurencin CT, Nukavarapu SP (2012) Bone tissue engineering: recent advances and challenges. Crit Rev Biomed Eng 40(5):363–408
Jeong CG, Zhang H, Hollister SJ (2012) Three-dimensional polycaprolactone scaffold-conjugated bone morphogenetic protein-2 promotes cartilage regeneration from primary chondrocytes in vitro and in vivo without accelerated endochondral ossification. J Biomed Mater Res A 100A(8):2088–2096
Chu CR, Dounchis JS, Yoshioka M, Sah RL, Coutts RD, Amiel D (1997) Osteochondral repair using perichondrial cells. A 1-year study in rabbits. Clin Orthop 340:220–229
Jiang C-C et al (2007) Repair of porcine articular cartilage defect with a biphasic osteochondral composite. J Orthop Res 25(10):1277–1290
Dresing I, Zeiter S, Auer J, Alini M, Eglin D (2014) Evaluation of a press-fit osteochondral poly(ester-urethane) scaffold in a rabbit defect model. J Mater Sci Mater Med 25(7):1691–1700
Frenkel SR et al (2005) Regeneration of articular cartilage—evaluation of osteochondral defect repair in the rabbit using multiphasic implants. Osteoarthritis Cartilage 13(9):798–807
Jeon JE, Vaquette C, Klein TJ, Hutmacher DW (2014) Perspectives in multiphasic osteochondral tissue engineering. Anat Rec 297(1):26–35
Marquass B et al (2010) A novel MSC-seeded triphasic construct for the repair of osteochondral defects. J Orthop Res Off Publ Orthop Res Soc 28(12):1586–1599
Da H et al (2013) The impact of compact layer in biphasic scaffold on osteochondral tissue engineering. PLoS One 8(1):e54838
Woodfield T b f, Blitterswijk CAV, Wijn JD, Sims T j, Hollander A p, Riesle J (2005) Polymer scaffolds fabricated with pore-size gradients as a model for studying the zonal organization within tissue-engineered cartilage constructs. Tissue Eng 11(9–10):1297–1311
Oh SH, Kim TH, Im GI, Lee JH (2010) Investigation of pore size effect on chondrogenic differentiation of adipose stem cells using a pore size gradient scaffold. Biomacromolecules 11(8):1948–1955
Karageorgiou V, Kaplan D (2005) Porosity of 3D biomaterial scaffolds and osteogenesis. Biomaterials 26(27):5474–5491
Eichmann A, Le Noble F, Autiero M, Carmeliet P (2005) Guidance of vascular and neural network formation. Curr Opin Neurobiol 15(1):108–115
Parent CA, Devreotes PN (1999) A cell’s sense of direction. Science 284(5415):765–770
Chen G, Deng C, Li Y-P (2012) TGF-β and BMP signaling in osteoblast differentiation and bone formation. Int J Biol Sci 8(2):272–288
Wozney JM (1992) The bone morphogenetic protein family and osteogenesis. Mol Reprod Dev 32(2):160–167
Nukavarapu SP, Laurencin CT, Amini AR, Dorcemus DL (2017) Gradient porous scaffolds. US 9,707,322 B2
Majumdar S, Pothirajan P, Dorcemus D, Nukavarapu S, Kotecha M (2016) High field sodium MRI assessment of stem cell chondrogenesis in a tissue-engineered matrix. Ann Biomed Eng 44(4):1120–1127
Dorcemus DL, Nukavarapu SP (2014) Novel and unique matrix design for osteochondral tissue engineering. MRS Online Proc Libr Arch 1621:17–23
Sherwood JK et al (2002) A three-dimensional osteochondral composite scaffold for articular cartilage repair. Biomaterials 23(24):4739–4751
Singh M et al (2010) Three-dimensional macroscopic scaffolds with a gradient in stiffness for functional regeneration of interfacial tissues. J Biomed Mater Res A 94(3):870–876
Guo J, Li C, Ling S, Huang W, Chen Y, Kaplan DL (2017) Multiscale design and synthesis of biomimetic gradient protein/biosilica composites for interfacial tissue engineering. Biomaterials 145(Supplement C):44–55
Liu C, Han Z, Czernuszka JT (2009) Gradient collagen/nanohydroxyapatite composite scaffold: development and characterization. Acta Biomater 5(2):661–669
Dormer NH, Singh M, Wang L, Berkland CJ, Detamore MS (2010) Osteochondral interface tissue engineering using macroscopic gradients of bioactive signals. Ann Biomed Eng 38(6):2167–2182
Dormer NH, Busaidy K, Berkland CJ, Detamore MS (2011) Osteochondral interface regeneration of rabbit mandibular condyle with bioactive signal gradients. J Oral Maxillofac Surg 69(6):e50–e57
Di Luca A, Klein-Gunnewiek M, Vancso JG, van Blitterswijk CA, Benetti EM, Moroni L (2017) Covalent binding of bone morphogenetic protein-2 and transforming growth factor-β3 to 3D plotted scaffolds for osteochondral tissue regeneration. Biotechnol J
Erisken C, Kalyon DM, Wang H, Örnek-Ballanco C, Xu J (2010) Osteochondral tissue formation through adipose-derived stromal cell differentiation on biomimetic polycaprolactone nanofibrous scaffolds with graded insulin and beta-glycerophosphate concentrations. Tissue Eng Part A 17(9–10):1239–1252
Kon E et al (2015) Osteochondral regeneration with a novel aragonite-hyaluronate biphasic scaffold: up to 12-month follow-up study in a goat model. J Orthop Surg 10
Kon E et al (2014) Osteochondral regeneration using a novel aragonite-hyaluronate bi-phasic scaffold in a goat model. Knee Surg Sports Traumatol Arthrosc 22(6):1452–1464
Demers C, Hamdy CR, Corsi K, Chellat F, Tabrizian M, Yahia L (2002) Natural coral exoskeleton as a bone graft substitute: a review. Biomed Mater Eng 12(1):15–35
Roudier M et al (1995) The resorption of bone-implanted corals varies with porosity but also with the host reaction. J Biomed Mater Res 29(8):909–915
Doherty MJ, Schlag G, Schwarz N, Mollan RA, Nolan PC, Wilson DJ (1994) Biocompatibility of xenogeneic bone, commercially available coral, a bioceramic and tissue sealant for human osteoblasts. Biomaterials 15(8):601–608
Petite H et al (2000) Tissue-engineered bone regeneration. Nat Biotechnol 18(9):959–963
Chung C, Burdick JA (2009) Influence of 3D hyaluronic acid microenvironments on mesenchymal stem cell chondrogenesis. Tissue Eng Part A 15(2):243–254
Amann E, Wolff P, Breel E, van Griensven M, Balmayor ER (2017) Hyaluronic acid facilitates chondrogenesis and matrix deposition of human adipose derived mesenchymal stem cells and human chondrocytes co-cultures. Acta Biomater 52(Supplement C):130–144
Kon E, Drobnic M, Davidson PA, Levy A, Zaslav K, Robinson D (2014) Chronic posttraumatic cartilage lesion of the knee treated with an acellular osteochondral-regenerating implant: case history with rehabilitation guidelines. J Sport Rehabil 23(3):270–275
Melton JTK, Wilson AJ, Chapman-Sheath P, Cossey AJ (2010) TruFit CB bone plug: chondral repair, scaffold design, surgical technique and early experiences. Expert Rev Med Devices 7(3):333–341
Verhaegen J, Clockaerts S, Van Osch GJVM, 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):12–19
Williams RJ, Gamradt SC (2008) Articular cartilage repair using a resorbable matrix scaffold. Instr Course Lect 57:563–571
Dhollander AAM et al (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. Arthrosc J Arthrosc Relat Surg 28(2):225–233
Saithna A, Dunne K, Kuchenbecker T, Thompson P, Dhillon M, Spalding T (2010) Qualitative MRI related to clinical results following cartilage repair using Trufit plugs: a two year follow up study. Orthop Proc 92-B(SUPP III):423
Joshi N, Reverte-Vinaixa M, Díaz-Ferreiro EW, Domínguez-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):1289–1295
Carmont MR, Carey-Smith R, Saithna A, Dhillon M, Thompson P, Spalding T (2009) Delayed incorporation of a TruFit plug: perseverance is recommended. Arthrosc J Arthrosc Relat Surg 25(7):810–814
Barber FA, Dockery WD (2011) A computed tomography scan assessment of synthetic multiphase polymer scaffolds used for osteochondral defect repair. Arthrosc J Arthrosc Relat Surg 27(1):60–64
Pearce CJ, Gartner LE, Mitchell A, Calder JD (2012) Synthetic osteochondral grafting of ankle osteochondral lesions. Foot Ankle Surg 18(2):114–118
Kon E, Filardo G, Perdisa F, Venieri G, Marcacci M (2014) Clinical results of multilayered biomaterials for osteochondral regeneration. J Exp Orthop 1:10
Delcogliano M et al (2014) Use of innovative biomimetic scaffold in the treatment for large osteochondral lesions of the knee. Knee Surg Sports Traumatol Arthrosc Off J ESSKA 22(6):1260–1269
Winthrop Z, Pinkowsky G, Hennrikus W (2015) Surgical treatment for osteochondritis dessicans of the knee. Curr Rev Musculoskelet Med 8(4):467–475
Kon E et al (2014) Clinical results and MRI evolution of a nano-composite multilayered biomaterial for osteochondral regeneration at 5 years. Am J Sports Med 42(1):158–165
Kon E, Delcogliano M, Filardo G, Busacca M, Di Martino A, Marcacci M (2011) Novel nano-composite multilayered biomaterial for osteochondral regeneration: a pilot clinical trial. Am J Sports Med 39(6):1180–1190
Brix M et al (2016) Successful osteoconduction but limited cartilage tissue quality following osteochondral repair by a cell-free multilayered nano-composite scaffold at the knee. Int Orthop 40(3):625–632
Christensen BB, Foldager CB, Jensen J, Jensen NC, Lind M (2016) Poor osteochondral repair by a biomimetic collagen scaffold: 1- to 3-year clinical and radiological follow-up. Knee Surg Sports Traumatol Arthrosc Off J ESSKA 24(7):2380–2387
Farr J, Gracitelli GC, Shah N, Chang EY, Gomoll AH (2016) High failure rate of a decellularized osteochondral allograft for the treatment of cartilage lesions. Am J Sports Med 44(8):2015–2022
Acknowledgements
The authors acknowledge support from AO Foundation, Musculoskeletal Transplant Foundation, and NSF (EFRI and AIR). Dr. Nukavarapu acknowledges funding from Bioscience Connecticut through Technology Translation Pipe-line program and University of Connecticut through SPARK technology commercialization program. Dr. Nukavarapu also acknowledges funding support from the National Institute of Biomedical Imaging and Bioengineering of the National Institutes of Health (Award Number R01EB020640).
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Spencer, V., Illescas, E., Maltes, L., Kim, H., Sathe, V., Nukavarapu, S. (2018). Osteochondral Tissue Engineering: Translational Research and Turning Research into Products. In: Oliveira, J., Pina, S., Reis, R., San Roman, J. (eds) Osteochondral Tissue Engineering. Advances in Experimental Medicine and Biology, vol 1058. Springer, Cham. https://doi.org/10.1007/978-3-319-76711-6_17
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