Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma to Enhance Osseous Integration Potential for Osteochondral Allografts

Aaron M. Stoker; Charles A. Baumann; James P. Stannard; James L. Cook

doi:10.1055/s-0037-1603800

The Journal of Knee Surgery, Table of Contents

J Knee Surg 2018; 31(04): 314-320
DOI: 10.1055/s-0037-1603800

Original Article

Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

Bone Marrow Aspirate Concentrate versus Platelet Rich Plasma to Enhance Osseous Integration Potential for Osteochondral Allografts

Authors

Aaron M. Stoker

¹Department of Orthopaedic Surgery/Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
Charles A. Baumann

¹Department of Orthopaedic Surgery/Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
James P. Stannard

¹Department of Orthopaedic Surgery/Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri
James L. Cook

¹Department of Orthopaedic Surgery/Thompson Laboratory for Regenerative Orthopaedics, Missouri Orthopaedic Institute, University of Missouri, Columbia, Missouri

Abstract

Fresh osteochondral allograft (OCA) transplantation is an attractive treatment option for symptomatic articular cartilage lesions in young, healthy patients. Since a lack of OCA bone integration can be a cause of treatment failure, methods for speeding and enhancing OCA bone integration to mitigate this potential complication are highly desirable. This study sought to determine and compare the potential of bone marrow aspirate concentrate (BMC) and leukoreduced platelet rich plasma (PRP) to repopulate the osseous portion of an OCA with cells and deliver osteogenic proteins. It was hypothesized that BMC would have significantly higher colony forming units (CFUs)/mL and seed the osseous portion of OCA with more cells than PRP. Finally, we hypothesized that the media of BMC and PRP treated OCAs would have significantly higher concentrations of osteogenic proteins compared with negative control OCAs. Cylindrical OCAs (n = 36) created from tissue stored for 21 days were treated with BMC (n = 12) or PRP (n = 12) obtained for 6 dogs, or left untreated as a negative control (n = 12). After treatment, OCAs were cultured for 7 or 14 days. Media were collected for analysis of osteogenic biomarker concentration. Samples of each BMC and PRP were tested for CFU concentration. On day 7 or 14, the grafts were assessed for cell surface adhesion and penetration using fluorescent microscopy. Significant differences in CFU and media biomarker concentration between the groups were determined using one-way analysis of variance (ANOVA) and Tukey's post-hoc test with the significance set at p < 0.05. Only OCAs saturated with BMC had viable cells detectable on the osseous portion of the allografts at day 7 and 14 of culture. BMC samples had a significantly higher (p = 0.029) CFU/mL compared with PRP samples. At day 3 and/or 7 of culture, the concentration of several osteogenic proteins was significantly higher in both BMC and PRP samples. Autogenous BMC can be used to deliver both a cell population and osteogenic proteins that may improve healing of the osseous portion of the OCA clinically.

Keywords

osteochondral allograft - bone marrow aspirate concentrate - platelet rich plasma - orthobiologic

Full Text

References

References
1 Hjelle K, Solheim E, Strand T, Muri R, Brittberg M. Articular cartilage defects in 1,000 knee arthroscopies. Arthroscopy 2002; 18 (07) 730-734
2 Widuchowski W, Widuchowski J, Trzaska T. Articular cartilage defects: study of 25,124 knee arthroscopies. Knee 2007; 14 (03) 177-182
3 Murphy RT, Pennock AT, Bugbee WD. Osteochondral allograft transplantation of the knee in the pediatric and adolescent population. Am J Sports Med 2014; 42 (03) 635-640
4 Pritzker KP, Gross AE, Langer F, Luk SC, Houpt JB. Articular cartilage transplantation. Hum Pathol 1977; 8 (06) 635-651
5 Marx RE, Carlson ER, Eichstaedt RM, Schimmele SR, Strauss JE, Georgeff KR. Platelet-rich plasma: growth factor enhancement for bone grafts. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 1998; 85 (06) 638-646
6 Weibrich G, Kleis WK, Hafner G, Hitzler WE. Growth factor levels in platelet-rich plasma and correlations with donor age, sex, and platelet count. J Craniomaxillofac Surg 2002; 30 (02) 97-102
7 Zhong W, Sumita Y, Ohba S. , et al. In vivo comparison of the bone regeneration capability of human bone marrow concentrates vs. platelet-rich plasma. PLoS One 2012; 7 (07) e40833
8 Wiltfang J, Kloss FR, Kessler P. , et al. Effects of platelet-rich plasma on bone healing in combination with autogenous bone and bone substitutes in critical-size defects. An animal experiment. Clin Oral Implants Res 2004; 15 (02) 187-193
9 Kanthan SR, Kavitha G, Addi S, Choon DS, Kamarul T. Platelet-rich plasma (PRP) enhances bone healing in non-united critical-sized defects: a preliminary study involving rabbit models. Injury 2011; 42 (08) 782-789
10 Kazakos K, Lyras DN, Thomaidis V. , et al. Application of PRP gel alone or in combination with guided bone regeneration does not enhance bone healing process: an experimental study in rabbits. J Craniomaxillofac Surg 2011; 39 (01) 49-53
11 Gerard D, Carlson ER, Gotcher JE, Jacobs M. Effects of platelet-rich plasma on the healing of autologous bone grafted mandibular defects in dogs. J Oral Maxillofac Surg 2006; 64 (03) 443-451
12 Boakye LA, Ross KA, Pinski JM. , et al. Platelet-rich plasma increases transforming growth factor-beta1 expression at graft-host interface following autologous osteochondral transplantation in a rabbit model. World J Orthop 2015; 6 (11) 961-969
13 Smyth NA, Haleem AM, Murawski CD, Do HT, Deland JT, Kennedy JG. The effect of platelet-rich plasma on autologous osteochondral transplantation: an in vivo rabbit model. J Bone Joint Surg Am 2013; 95 (24) 2185-2193
14 Yin W, Qi X, Zhang Y. , et al. Advantages of pure platelet-rich plasma compared with leukocyte- and platelet-rich plasma in promoting repair of bone defects. J Transl Med 2016; 14: 73
15 Kobayashi Y, Saita Y, Nishio H. , et al. Leukocyte concentration and composition in platelet-rich plasma (PRP) influences the growth factor and protease concentrations. J Orthop Sci 2016; 21 (05) 683-689
16 Sundman EA, Cole BJ, Fortier LA. Growth factor and catabolic cytokine concentrations are influenced by the cellular composition of platelet-rich plasma. Am J Sports Med 2011; 39 (10) 2135-2140
17 Smyth NA, Murawski CD, Haleem AM, Hannon CP, Savage-Elliott I, Kennedy JG. Establishing proof of concept: platelet-rich plasma and bone marrow aspirate concentrate may improve cartilage repair following surgical treatment for osteochondral lesions of the talus. World J Orthop 2012; 3 (07) 101-108
18 Dawson JI, Smith JO, Aarvold A. , et al. Enhancing the osteogenic efficacy of human bone marrow aspirate: concentrating osteoprogenitors using wave-assisted filtration. Cytotherapy 2013; 15 (02) 242-252
19 Fortier LA, Potter HG, Rickey EJ. , et al. Concentrated bone marrow aspirate improves full-thickness cartilage repair compared with microfracture in the equine model. J Bone Joint Surg Am 2010; 92 (10) 1927-1937
20 Shapiro E, Grande D, Drakos M. Biologics in Achilles tendon healing and repair: a review. Curr Rev Musculoskelet Med 2015; 8 (01) 9-17
21 Gianakos A, Ni A, Zambrana L, Kennedy JG, Lane JM. Bone marrow aspirate concentrate in animal long bone healing: an analysis of basic science evidence. J Orthop Trauma 2016; 30 (01) 1-9
22 Fortier LA, Barker JU, Strauss EJ, McCarrel TM, Cole BJ. The role of growth factors in cartilage repair. Clin Orthop Relat Res 2011; 469 (10) 2706-2715
23 Ardjomandi N, Duttenhoefer F, Xavier S, Oshima T, Kuenz A, Sauerbier S. In vivo comparison of hard tissue regeneration with ovine mesenchymal stem cells processed with either the FICOLL method or the BMAC method. J Craniomaxillofac Surg 2015; 43 (07) 1177-1183
24 Sauerbier S, Stricker A, Kuschnierz J. , et al. In vivo comparison of hard tissue regeneration with human mesenchymal stem cells processed with either the FICOLL method or the BMAC method. Tissue Eng Part C Methods 2010; 16 (02) 215-223
25 Bourzac C, Smith LC, Vincent P, Beauchamp G, Lavoie JP, Laverty S. Isolation of equine bone marrow-derived mesenchymal stem cells: a comparison between three protocols. Equine Vet J 2010; 42 (06) 519-527
26 Jäger M, Herten M, Fochtmann U. , et al. Bridging the gap: bone marrow aspiration concentrate reduces autologous bone grafting in osseous defects. J Orthop Res 2011; 29 (02) 173-180
27 Bastian JD, Egli RJ, Ganz R, Hofstetter W, Leunig M. Chondrocytes within osteochondral grafts are more resistant than osteoblasts to tissue culture at 37°C. J Invest Surg 2011; 24 (01) 28-34
28 Gessmann J, Köller M, Godry H, Schildhauer TA, Seybold D. Regenerate augmentation with bone marrow concentrate after traumatic bone loss. Orthop Rev (Pavia) 2012; 4 (01) e14
29 Sununliganon L, Peng L, Singhatanadgit W, Cheung LK. Osteogenic efficacy of bone marrow concentrate in rabbit maxillary sinus grafting. J Craniomaxillofac Surg 2014; 42 (08) 1753-1765
30 Chahla J, Dean CS, Moatshe G, Pascual-Garrido C, Serra Cruz R, LaPrade RF. Concentrated bone marrow aspirate for the treatment of chondral injuries and osteoarthritis of the knee: a systematic review of outcomes. Orthop J Sports Med 2016; 4 (01) 2325967115625481
31 Holton J, Imam MA, Snow M. Bone marrow aspirate in the treatment of chondral injuries. Front Surg 2016; 3: 33
32 Emmerson BC, Görtz S, Jamali AA, Chung C, Amiel D, Bugbee WD. Fresh osteochondral allografting in the treatment of osteochondritis dissecans of the femoral condyle. Am J Sports Med 2007; 35 (06) 907-914
33 Aubin PP, Cheah HK, Davis AM, Gross AE. Long-term followup of fresh femoral osteochondral allografts for posttraumatic knee defects. Clin Orthop Relat Res 2001; ; (391, Suppl) S318-S327
34 McCulloch PC, Kang RW, Sobhy MH, Hayden JK, Cole BJ. Prospective evaluation of prolonged fresh osteochondral allograft transplantation of the femoral condyle: minimum 2-year follow-up. Am J Sports Med 2007; 35 (03) 411-420
35 Czitrom AA, Keating S, Gross AE. The viability of articular cartilage in fresh osteochondral allografts after clinical transplantation. J Bone Joint Surg Am 1990; 72 (04) 574-581
36 Ranawat AS, Vidal AF, Chen CT, Zelken JA, Turner AS, Williams III RJ. Material properties of fresh cold-stored allografts for osteochondral defects at 1 year. Clin Orthop Relat Res 2008; 466 (08) 1826-1836
37 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
38 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
39 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
40 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
41 Chu CR, Convery FR, Akeson WH, Meyers M, Amiel D. Articular cartilage transplantation. Clinical results in the knee. Clin Orthop Relat Res 1999; (360) 159-168
42 Deschaseaux F, Sensébé L, Heymann D. Mechanisms of bone repair and regeneration. Trends Mol Med 2009; 15 (09) 417-429
43 Rickard DJ, Sullivan TA, Shenker BJ, Leboy PS, Kazhdan I. Induction of rapid osteoblast differentiation in rat bone marrow stromal cell cultures by dexamethasone and BMP-2. Dev Biol 1994; 161 (01) 218-228
44 Deckers MM, Van Bezooijen RL, Van Der Horst G. , et al. Bone morphogenetic proteins stimulate angiogenesis through osteoblast-derived vascular endothelial growth factor A. Endocrinology 2002; 143 (04) 1545-1553
45 Arpornmaeklong P, Kochel M, Depprich R, Kübler NR, Würzler KK. Influence of platelet-rich plasma (PRP) on osteogenic differentiation of rat bone marrow stromal cells. An in vitro study. Int J Oral Maxillofac Surg 2004; 33 (01) 60-70
46 Kon T, Cho TJ, Aizawa T. , et al. Expression of osteoprotegerin, receptor activator of NF-kappaB ligand (osteoprotegerin ligand) and related proinflammatory cytokines during fracture healing. J Bone Miner Res 2001; 16 (06) 1004-1014
47 Gerstenfeld LC, Cho TJ, Kon T. , et al. Impaired fracture healing in the absence of TNF-α signaling: the role of TNF-α in endochondral cartilage resorption. J Bone Miner Res 2003; 18 (09) 1584-1592
48 Simonet WS, Lacey DL, Dunstan CR. , et al. Osteoprotegerin: a novel secreted protein involved in the regulation of bone density. Cell 1997; 89 (02) 309-319
49 Zaidi M, Sun L, Robinson LJ. , et al. ACTH protects against glucocorticoid-induced osteonecrosis of bone. Proc Natl Acad Sci U S A 2010; 107 (19) 8782-8787
50 Minetto M, Reimondo G, Osella G, Ventura M, Angeli A, Terzolo M. Bone loss is more severe in primary adrenal than in pituitary-dependent Cushing's syndrome. Osteoporos Int 2004; 15 (11) 855-861
51 Elias LL, Huebner A, Metherell LA. , et al. Tall stature in familial glucocorticoid deficiency. Clin Endocrinol (Oxf) 2000; 53 (04) 423-430
52 Golub EE, Boesze-Battaglia K. The role of alkaline phosphatase in mineralization. Curr Opin Orthop 2007; 18 (05) 444-448
53 Rozila I, Azari P, Munirah S. , et al. Differential osteogenic potential of human adipose-derived stem cells co-cultured with human osteoblasts on polymeric microfiber scaffolds. J Biomed Mater Res A 2016; 104 (02) 377-387
54 Zhao Y, Zou B, Shi Z, Wu Q, Chen GQ. The effect of 3-hydroxybutyrate on the in vitro differentiation of murine osteoblast MC3T3-E1 and in vivo bone formation in ovariectomized rats. Biomaterials 2007; 28 (20) 3063-3073
55 Hong D, Chen HX, Yu HQ. , et al. Morphological and proteomic analysis of early stage of osteoblast differentiation in osteoblastic progenitor cells. Exp Cell Res 2010; 316 (14) 2291-2300
56 An G, Xue Z, Zhang B, Deng QK, Wang YS, Lv SC. Expressing osteogenic growth peptide in the rabbit bone mesenchymal stem cells increased alkaline phosphatase activity and enhanced the collagen accumulation. Eur Rev Med Pharmacol Sci 2014; 18 (11) 1618-1624
57 Seyedjafari E, Soleimani M, Ghaemi N, Sarbolouki MN. Enhanced osteogenic differentiation of cord blood-derived unrestricted somatic stem cells on electrospun nanofibers. J Mater Sci Mater Med 2011; 22 (01) 165-174
58 Bajada S, Marshall MJ, Wright KT, Richardson JB, Johnson WEB. Decreased osteogenesis, increased cell senescence and elevated Dickkopf-1 secretion in human fracture non union stromal cells. Bone 2009; 45 (04) 726-735
59 Mason JJ, Williams BO. SOST and DKK: antagonists of LRP family signaling as targets for treating bone disease. J Osteoporos 2010; 2010: pii :460120
60 Florio M, Gunasekaran K, Stolina M. , et al. A bispecific antibody targeting sclerostin and DKK-1 promotes bone mass accrual and fracture repair. Nat Commun 2016; 7: 11505
61 Baron R, Kneissel M. WNT signaling in bone homeostasis and disease: from human mutations to treatments. Nat Med 2013; 19 (02) 179-192
62 Delforge M, Terpos E, Richardson PG. , et al. Fewer bone disease events, improvement in bone remodeling, and evidence of bone healing with bortezomib plus melphalan-prednisone vs. melphalan-prednisone in the phase III VISTA trial in multiple myeloma. Eur J Haematol 2011; 86 (05) 372-384
63 Politou MC, Heath DJ, Rahemtulla A. , et al. Serum concentrations of Dickkopf-1 protein are increased in patients with multiple myeloma and reduced after autologous stem cell transplantation. Int J Cancer 2006; 119 (07) 1728-1731