Systematic Review of Osteochondral Allograft Transplant Immunology: How We Can Further Optimize Outcomes

Josephine Luk; Aaron M. Stoker; Emma Teixeiro; Keiichi Kuroki; Anna J. Schreiner; James P. Stannard; Robert Wissman; James L. Cook

doi:10.1055/s-0040-1721670

The Journal of Knee Surgery, Table of Contents

J Knee Surg 2021; 34(01): 030-038
DOI: 10.1055/s-0040-1721670

Special Focus Section

Systematic Review of Osteochondral Allograft Transplant Immunology: How We Can Further Optimize Outcomes

Josephine Luk

¹Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri

²Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri

,

Aaron M. Stoker

¹Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri

²Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri

,

Emma Teixeiro

³Department of Molecular Microbiology and Immunology, University of Missouri, Columbia, Missouri

,

Keiichi Kuroki

¹Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri

,

Anna J. Schreiner

¹Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri

⁴BG Center for Trauma and Reconstructive Surgery, Eberhard Karls University of Tübingen, Tübingen, Germany

,

James P. Stannard

¹Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri

²Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri

,

Robert Wissman

⁵Department of Radiology, University of Missouri, Columbia, Missouri

,

James L. Cook

¹Thompson Laboratory for Regenerative Orthopaedics, University of Missouri, Columbia, Missouri

²Department of Orthopaedic Surgery, University of Missouri, Columbia, Missouri

› Author Affiliations

Abstract

Despite the growing success for osteochondral allograft (OCA) transplantation in treating large articular cartilage lesions in multiple joints, associated revision and failure rates are still higher than desired. While immunorejection responses have not been documented, the effects of the host's immune responses on OCA transplantation failures have not been thoroughly characterized. The objective of this study was to systematically review clinically relevant peer-reviewed evidence pertaining to the immunology of OCAs to elucidate theragnostic strategies for improving functional graft survival and outcomes for patients undergoing OCA transplantation. This systematic review of Cochrane Central Register of Controlled Trials, the Cochrane Database of Systematic Reviews, MEDLINE, PubMed, and EMBASE suggests that host immune responses play key roles in incorporation and functional survival of OCA transplants. OCA rejection has not been reported; however, graft integration through creeping substitution is reliant on host immune responses. Prolonged inflammation, diminished osteogenic potential for healing and incorporation, and relative bioburden are mechanisms that may be influenced by the immune system and contribute to undesirable outcomes after OCA transplantation. Based on the safety and efficacy of OCA transplantation and its associated benefits to a large and growing patient population, basic, preclinical, and clinical osteoimmunological studies on OCA transplantation that comprehensively assess and correlate cellular, molecular, histologic, biomechanical, biomarkers, diagnostic imaging, arthroscopic, functional, and patient-reported outcome measures are of high interest and importance.

Keywords

osteochondral allograft - transplantation - immunology - knee - cartilage

Full Text

References

References
1 Stannard JP, Cook JL. Prospective assessment of outcomes after primary unipolar, multisurface, and bipolar osteochondral allograft transplantations in the knee: a comparison of 2 preservation methods. Am J Sports Med 2020; 48 (06) 1356-1364
2 Familiari F, Cinque ME, Chahla J. et al. Clinical outcomes and failure rates of osteochondral allograft transplantation in the knee: a systematic review. Am J Sports Med 2018; 46 (14) 3541-3549
3 Levy YD, Görtz S, Pulido PA, McCauley JC, Bugbee WD. Do fresh osteochondral allografts successfully treat femoral condyle lesions?. Clin Orthop Relat Res 2013; 471 (01) 231-237
4 Sherman SL, Garrity J, Bauer K, Cook J, Stannard J, Bugbee W. Fresh osteochondral allograft transplantation for the knee: current concepts. J Am Acad Orthop Surg 2014; 22 (02) 121-133
5 Farr J, Cole B, Dhawan A, Kercher J, Sherman S. Clinical cartilage restoration: evolution and overview. Clin Orthop Relat Res 2011; 469 (10) 2696-2705
6 Cook JL, Stannard JP, Stoker AM. et al. Importance of donor chondrocyte viability for osteochondral allografts. Am J Sports Med 2016; 44 (05) 1260-1268
7 Nuelle CW, Nuelle JAV, Cook JL, Stannard JP. Patient factors, donor age, and graft storage duration affect osteochondral allograft outcomes in knees with or without comorbidities. J Knee Surg 2017; 30 (02) 179-184
8 Gibon E, Lu L, Goodman SB. Aging, inflammation, stem cells, and bone healing. Stem Cell Res Ther 2016; 7 (01) 44
9 Pearson RG, Clement RGE, Edwards KL, Scammell BE. Do smokers have greater risk of delayed and non-union after fracture, osteotomy and arthrodesis? A systematic review with meta-analysis. BMJ Open 2016; 6 (11) e010303
10 Sirlin CB, Brossmann J, Boutin RD. et al. Shell osteochondral allografts of the knee: comparison of mr imaging findings and immunologic responses. Radiology 2001; 219 (01) 35-43
11 Stevenson S, Li XQ, Martin B. The fate of cancellous and cortical bone after transplantation of fresh and frozen tissue-antigen-matched and mismatched osteochondral allografts in dogs. J Bone Joint Surg Am 1991; 73 (08) 1143-1156
12 Stoker AM, Stannard JP, Cook JL. Chondrocyte viability at time of transplantation for osteochondral allografts preserved by the Missouri Osteochondral Preservation System versus standard tissue bank protocol. J Knee Surg 2018; 31 (08) 772-780
13 Wiley AM, Kosinka E. Experimental and clinical aspects of transplantation of entire hyaline cartilage surfaces. J Am Geriatr Soc 1974; 22 (12) 547-550
14 Williams SK, Amiel D, Ball ST. et al. Analysis of cartilage tissue on a cellular level in fresh osteochondral allograft retrievals. Am J Sports Med 2007; 35 (12) 2022-2032
15 Oakeshott RD, Farine I, Pritzker KP, Langer F, Gross AE. A clinical and histologic analysis of failed fresh osteochondral allografts. Clin Orthop Relat Res 1988; (233) 283-294
16 Hayden JA, van der Windt DA, Cartwright JL, Côté P, Bombardier C. Assessing bias in studies of prognostic factors. Ann Intern Med 2013; 158 (04) 280-286
17 Tschon M, Veronesi F, Giannini S, Fini M. Fresh osteochondral allotransplants: outcomes, failures and future developments. Injury 2017; 48 (07) 1287-1295
18 Bugbee WD, Pallante-Kichura AL, Görtz S, Amiel D, Sah R. Osteochondral allograft transplantation in cartilage repair: graft storage paradigm, translational models, and clinical applications. J Orthop Res 2016; 34 (01) 31-38
19 Langer F, Czitrom A, Pritzker KP, Gross AE. The immunogenicity of fresh and frozen allogeneic bone. J Bone Joint Surg Am 1975; 57 (02) 216-220
20 Langer F, Gross AE. Immunogenicity of allograft articular cartilage. J Bone Joint Surg Am 1974; 56 (02) 297-304
21 Langer F, Gross AE, West M, Urovitz EP. The immunogenicity of allograft knee joint transplants. Clin Orthop Relat Res 1978; (132) 155-162
22 Stoker AM, Stannard JP, Kuroki K, Bozynski CC, Pfeiffer FM, Cook JL. Validation of the Missouri Osteochondral Allograft Preservation System for the maintenance of osteochondral allograft quality during prolonged storage. Am J Sports Med 2018; 46 (01) 58-65
23 Stevenson S, Horowitz M. The response to bone allografts. J Bone Joint Surg Am 1992; 74 (06) 939-950
24 Nordström DC, Santavirta S, Aho A, Heikkilä J, Teppo AM, Konttinen YT. Immune responses to osteoarticular allografts of the knee--cytokine studies. Arch Orthop Trauma Surg 1999; 119 (3-4): 195-198
25 Stevenson S, Shaffer JW, Goldberg VM. The humoral response to vascular and nonvascular allografts of bone. Clin Orthop Relat Res 1996; (326) 86-95
26 Toben D, Schroeder I, El Khassawna T. et al. Fracture healing is accelerated in the absence of the adaptive immune system. J Bone Miner Res 2011; 26 (01) 113-124
27 Liu Z, Fan H, Jiang S. CD4(+) T-cell subsets in transplantation. Immunol Rev 2013; 252 (01) 183-191
28 Spahn JH, Li W, Kreisel D. Innate immune cells in transplantation. Curr Opin Organ Transplant 2014; 19 (01) 14-19
29 Stevenson S. The immune response to osteochondral allografts in dogs. J Bone Joint Surg Am 1987; 69 (04) 573-582
30 Elves MW. Immunological studies of osteoarticular allografts. Proc R Soc Med 1971; 64 (06) 644
31 Elves MW. Newer knowledge of the immunology of bone and cartilage. Clin Orthop Relat Res 1976; (120) 232-259
32 Phipatanakul WP, VandeVord PJ, Teitge RA, Wooley PH. Immune response in patients receiving fresh osteochondral allografts. Am J Orthop Belle Mead NJ 2004; 33 (07) 345-348
33 Osiecka-Iwan A, Hyc A, Radomska-Leśniewska DM, Rymarczyk A, Skopiński P. Antigenic and immunogenic properties of chondrocytes. Implications for chondrocyte therapeutic transplantation and pathogenesis of inflammatory and degenerative joint diseases. Cent Eur J Immunol 2018; 43 (02) 209-219
34 Ambra LF, de Girolamo L, Gomoll AH. Pulse lavage fails to significantly reduce bone marrow content in osteochondral allografts: a histological and DNA quantification study. Am J Sports Med 2019; 47 (11) 2723-2728
35 Baumann CA, Baumann JR, Bozynski CC, Stoker AM, Stannard JP, Cook JL. Comparison of techniques for preimplantation treatment of osteochondral allograft bone. J Knee Surg 2019; 32 (01) 97-104
36 Cook JL, Stoker AM, Stannard JP. et al. A novel system improves preservation of osteochondral allografts. Clin Orthop Relat Res 2014; 472 (11) 3404-3414
37 Görtz S, Bugbee WD. Fresh osteochondral allografts: graft processing and clinical applications. J Knee Surg 2006; 19 (03) 231-240
38 Innis PC, Randolph MA, Paskert JP. et al. Vascularized bone allografts: in vitro assessment of cell-mediated and humoral responses. Plast Reconstr Surg 1991; 87 (02) 315-325
39 Guder C, Gravius S, Burger C, Wirtz DC, Schildberg FA. Osteoimmunology: a current update of the interplay between bone and the immune system. Front Immunol 2020; 11: 58
40 Friedlaender GE, Horowitz MC. Immune responses to osteochondral allografts: nature and significance. Orthopedics 1992; 15 (10) 1171-1175
41 Johnson KA. Immune system and bone regeneration. Vet Comp Orthop Traumatol 2015; 28 (04) V-VI
42 Ono T, Takayanagi H. Osteoimmunology in bone fracture healing. Curr Osteoporos Rep 2017; 15 (04) 367-375
43 Kovach TK, Dighe AS, Lobo PI, Cui Q. Interactions between MSCs and immune cells: implications for bone healing. J Immunol Res 2015; 2015: 752510
44 Baht GS, Vi L, Alman BA. The role of the immune cells in fracture healing. Curr Osteoporos Rep 2018; 16 (02) 138-145
45 Bahney CS, Zondervan RL, Allison P. et al. Cellular biology of fracture healing. J Orthop Res 2019; 37 (01) 35-50
46 El-Jawhari JJ, Jones E, Giannoudis PV. The roles of immune cells in bone healing; what we know, do not know and future perspectives. Injury 2016; 47 (11) 2399-2406
47 Gardner ROE, Bates JH, Ng'oma E, Harrison WJ. Fracture union following internal fixation in the HIV population. Injury 2013; 44 (06) 830-833
48 Bajada S, Harrison PE, Ashton BA, Cassar-Pullicino VN, Ashammakhi N, Richardson JB. Successful treatment of refractory tibial nonunion using calcium sulphate and bone marrow stromal cell implantation. J Bone Joint Surg Br 2007; 89 (10) 1382-1386
49 Friedlaender GE. Immune responses to osteochondral allografts. Current knowledge and future directions. Clin Orthop Relat Res 1983; (174) 58-68
50 Burchardt H. The biology of bone graft repair. Clin Orthop Relat Res 1983; (174) 28-42
51 van Dijk CN. Editorial commentary: bulk osteochondral talar grafts compromise future arthrodesis or prosthesis. Arthroscopy 2017; 33 (01) 223-224
52 Kandel RA, Gross AE, Ganel A, McDermott AG, Langer F, Pritzker KP. Histopathology of failed osteoarticular shell allografts. Clin Orthop Relat Res 1985; (197) 103-110
53 Stevenson S, Hohn RB, Templeton JW. Effects of tissue antigen matching on the healing of fresh cancellous bone allografts in dogs. Am J Vet Res 1983; 44 (02) 201-206
54 Wendler S, Schlundt C, Bucher CH. et al. Immune modulation to enhance bone healing—a new concept to induce bone using prostacyclin to locally modulate immunity. Front Immunol 2019; 10: 713
55 Grant JA. Outcomes associated with return to sports following osteochondral allograft transplant in the knee: a scoping review. Curr Rev Musculoskelet Med 2019; 12 (02) 181-189
56 Stoker AM, Baumann CA, Stannard JP, Cook JL. Bone marrow aspirate concentrate versus platelet rich plasma to enhance osseous integration potential for osteochondral allografts. J Knee Surg 2018; 31 (04) 314-320
57 Cook JL. Editorial commentary: Bone marrow aspirate biologics for osteochondral allografts-because we can or because we should?. Arthroscopy 2019; 35 (08) 2445-2447
58 Ackermann J, Mestriner AB, Shah N, Gomoll AH. Effect of autogenous bone marrow aspirate treatment on magnetic resonance imaging integration of osteochondral allografts in the knee: a matched comparative imaging analysis. Arthroscopy 2019; 35 (08) 2436-2444
59 Haimi S, Wahlman M, Mannila M, Virtanen V, Hirn M. Pulse-lavage washing is an effective method for defatting of morselized allograft bone in the operating theater. Acta Orthop 2008; 79 (01) 94-97
60 Meyer MA, McCarthy MA, Gitelis ME. et al. Effectiveness of lavage techniques in removing immunogenic elements from osteochondral allografts. Cartilage 2017; 8 (04) 369-373
61 Sun Y, Jiang W, Cory E. et al. Pulsed lavage cleansing of osteochondral grafts depends on lavage duration, flow intensity, and graft storage condition. PLoS One 2017; 12 (05) e0176934
62 Wang D, Lin KM, Burge AJ, Balazs GC, Williams III RJ. Bone marrow aspirate concentrate does not improve osseous integration of osteochondral allografts for the treatment of chondral defects in the knee at 6 and 12 months: a comparative magnetic resonance imaging analysis. Am J Sports Med 2019; 47 (02) 339-346