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Enhancing the Functionality of Trabecular Allografts Through Polymeric Coating for Factor Loading

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Abstract

Allografts are commonly used as an alternative to autografts for bone defect repair, but in some instances suffer from reduced host incorporation that can lead to complications 5 and 10 years post-implantation. We have previously demonstrated that using a thin polymeric coating along the outer surfaces of cortical bone can improve the biofunctionality of devitalized bone allografts by permitting the upload and delivery of growth factors from the thin coating. Here, we expand on our previous work to develop a methodology to coat porous trabecular allografts with a similar polymer coating with careful attention to maintaining an open pore network within the allograft and establishing the effect of varying the polymer solution viscosity on coating extent and thickness. Results indicate that varying the polymer solution viscosity by changing the polymer to solvent ratio used to coat the samples allows for variations in coating thickness and extent of surface area coverage, each perhaps allowing for greater control over growth factor loading and release concentration and kinetics. Further, we develop a dynamic coating method that produces a continuous and consistent coating throughout the pore structure vs. the previously used static method that resulted in a discontinuous coating throughout the pore network. The work demonstrated here provides important techniques for varying the payload of polymer-coated, factor-loaded trabecular allografts which would provide another tool to the orthopedic surgeon when healing large-scale defects with trabecular allograft.

Lay Summary

Large scale bone defects are traditionally treated with either autografts or allografts. Allografts suffer from poor incorporation in part due to the processing undertaken to render them safe to transplant from one individual to another. We sought to add back some of the biological functionality that is removed in this processing by loading growth factors into a very thin polymeric coating that we apply to the surface of the allograft. Our results indicate a thin, continuous polymeric coating throughout the trabecular allograft, with the amount of this coating varying as we vary the concentration of this polymer solution prior to coating.

Future studies will evaluate the ability of this varied concentration of polymer coating to permit the delivery of varying amounts of growth factors, imparting a greater degree of control over the amount of growth factor delivered from the coated allografts.

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References

  1. Giannoudis PV, Dinopoulos H, Tsiridis E. Bone substitutes: an update. Injury. 2005;36(suppl 3):S20–7.

    Article  Google Scholar 

  2. Fleming JE, Cornell CN, Muschler GF. Bone cells and matrices in orthopedic tissue engineering. Orthop Clin of North America. 2000;31(3):357–74.

    Article  Google Scholar 

  3. CDC first document Center for Disease Control. Septic arthritis following anterior cruciate ligament reconstruction using tendon allografts—Florida and Louisiana, 2000. Morb Mortal Wkly Rep. 2001;50(48):1081–3.

    Google Scholar 

  4. CDC second document Center for Disease Control. Update: allograft-associated bacterial infections—United States, 2002. Morb Mortal Wkly Rep. 2002;51(10):207–10.

    Google Scholar 

  5. Wheeler DL, Enneking WF. Allograft bone decreases in strength in vivo over time. Clin Orthop Rel Res. 2005;435:36–42.

    Article  Google Scholar 

  6. Hornicek F, Gebhardt M, Tomford W. Factors affecting nonunion of the allograft-host junction. Clin Orthop. 2001;382:87–98.

    Article  Google Scholar 

  7. Lord CF, Gebhardt MC, Tomford WW, Mankin HJ. Infection in bone allografts: incidence, nature, and treatment. J Bone Joint Surg. 1988;70A:369–76.

    Article  Google Scholar 

  8. Stevenson S, Horowitz M. The response to bone allografts. J Bone Joint Surg. 1992;74A:939–51.

    Article  Google Scholar 

  9. Whiteside LA, Picalho PS. Radiologic and histologic analysis of morselized allograft in revision total knee replacement. Clin Orthop Relat Res. 1998;357:149–56.

    Article  Google Scholar 

  10. Leopold SS, Jacobs JJ, Rosenberg AG. Cancellous allograft in revision total hip arthroplasty. Clin Orthop Rel Res. 2000;371:86–97.

    Article  Google Scholar 

  11. Ito H, Koefoed M, Tiyapatanaputi P, Gromov K, Goater JJ, Carmouche J, Zhang X, Rubery PT, Rabinowitz J, Samulski RJ, Nakamura T, Soballe K, O'Keefe RJ, Boyce BF, Schwarz EM. Remodeling of cortical bone allografts mediated by adherent rAAV-RANKL and VEGF gene therapy. Nat Med. 2005;11(3):291–7.

    Article  Google Scholar 

  12. Dallari D, Fini M, Stagni C, Torricelli P, Nicoli Aldini N, Giavaresi G, Cenni E, Baldini N, Cenacchi A, Bassi A, Giardino R, Fornasari PM, Giunti A. In vivo study on the healing of bone defects treated with bone marrow stromal cells, platelet-rich plasma, and freeze-dried bone allografts, alone and in combination. J Orthop Res. 2006;24(5):877–88.

    Article  Google Scholar 

  13. Koefoed M, Ito H, Gromov K, Reynolds DG, Awad HA, Rubery PT, Ulrich-Vinther M, Soballe K, Guldberg RE, Lin AS, O'Keefe RJ, Zhang X, Schwarz EM. Biological effects of rAAV-caAlk2 coating on structural allograft healing. Mol Ther. 2005;12(2):212–8.

    Article  Google Scholar 

  14. Fini M, Giavaresi G, Aldini NN, Torricelli P, Botter R, Beruto D, Giardino R. A bone substitute composed of polymethylmethacrylate and -tricalcium phosphate: results in terms of osteoblast function and bone tissue formation. Biomaterials. 2002;23:4523–31.

    Article  Google Scholar 

  15. Kikuchi M, Itoh S, Ichinose S, Shinomiya K, Tanaka J. Self-organization mechanism in a bone-like hydroxyapatite/collagen nanocomposite synthesized in vitro and its biological reaction in vivo. Biomaterials. 2001;22:1705–11.

    Article  Google Scholar 

  16. Chen F, Wang ZC, Lin CJ. Preparation and characterization of nano-sized hydroxyapatite particles and hydroxyapatite/chitosan nano-composite for use in biomedical materials. Mater Lett. 2002;57:858–61.

    Article  Google Scholar 

  17. Borden M, Attawia M, Khan Y, Laurencin CT. Tissue engineered microsphere-based matrices for bone repair: design and evaluation. Biomaterials. 2002;23(2):551–9.

    Article  Google Scholar 

  18. Khan Y, Katti DS, Laurencin CT. A novel polymer-synthesized ceramic composite based system for bone repair: osteoblast growth on scaffolds with varied calcium phosphate content. Nanoscale Materials Science in Biology and Medicine. Editors: C.T. Laurencin, E. Botchwey MRS Proceedings Volume 845.

  19. Khan Y, Katti DS, Laurencin CT. A novel polymer-synthesized ceramic composite based system for bone repair: an in vitro evaluation. J Biomed Mater Res. 2004;69A:728–37.

    Article  Google Scholar 

  20. Baas J, Elmengaard B, Jensen TB, Jakobsen T, et al. The effect of pretreating morselized allograft bone with rhBMP-2 and/or pamidronate on the fixation of porous Ti and HA-coated implants. Biomaterials. 2008;29(19):2915–22.

    Article  Google Scholar 

  21. Lieberman JR, Conduah A, Urist MR. Treatment of osteonecrosis of the femoral head with core decompression and human bone morphogenetic protein. Clin Orthop Relat Res. 2004;429:139–45.

    Article  Google Scholar 

  22. Jakobsen T, Baas J, Bechtold JE, Elmengaard B, Søballe K. Soaking morselized allograft in bisphosphonate can impair implant fixation. Clin Orthop Relat Res. 2007;463:195–201.

    Google Scholar 

  23. Jakobsen T, Baas J, Kold S, Bechtold JE, Elmengaard B, Søballe K. Local bisphosphonate treatment increases fixation of hydroxyapatite-coated implants inserted with bone compaction. J Orthop Res. 2009;27(2):189–94.

    Article  Google Scholar 

  24. Zhang X, Awad HA, O’Keefe RJ, Guldberg RE, Schwarz EM. Engineering periosteum for structural bone graft healing. Clin Orthop Relat Res. 2008;466:1777–87.

    Article  Google Scholar 

  25. Knothe Tate ML, Ritzman TF, Schneider E, Knothe UR. Testing of a new one-stage bone-transport surgical procedure exploiting the periosteum for the repair of long-bone defects. J Bone Joint Surg Am. 2007;89:307–16.

    Article  Google Scholar 

  26. Ouyang HW, Cao T, Zou XH, Heng BC, Wang LL, Song XH, Huang HF. Mesenchymal stem cell sheets revitalize nonviable dense grafts: implications for repair of large-bone and tendon defects. Transplantation. 2006;82:170–4.

    Article  Google Scholar 

  27. Zhou Y, Chen F, Ho ST, Woodruff MA, Lim TM, Hutmacher DW. Combined marrow stromal cell-sheet techniques and high strength biodegradable composite scaffolds for engineered functional bone grafts. Biomaterials. 2007;28:814–24.

    Article  Google Scholar 

  28. Lewandrowski KU, Bondre SP, Gresser JD, Wise DL, Tomford WW, Trantolo DJ. Improved osteoconduction of cortical bone grafts by biodegradable foam coating. Biomed Mater Eng. 1999;9(5–6):265–75.

    Google Scholar 

  29. Lewandrowski KU, Bondre S, Hile DD, Thompson BM, Wise DL, Tomford WW, Trantolo DJ. Porous poly(propylene fumarate) foam coating of orthotopic cortical bone grafts for improved osteoconduction. Tissue Eng. 2002;8(6):1017–27.

    Article  Google Scholar 

  30. Sharmin F, Adams D, Pensak M, Dukas A, Lieberman J, Khan Y. Biofunctionalizing devitalized bone allografts through polymer-mediated short and long term growth factor delivery. J Biomed Mater Res A. 2015;103(9):2847–54.

    Article  Google Scholar 

  31. Sharmin F, McDermott C, Lieberman J, Sanjay A, Khan Y. Dual growth factor delivery from biofunctionalized allografts: sequential VEGF and BMP-2 release to stimulate allograft remodeling. J Orthop Res Accepted Author Manuscript. 2016; doi:10.1002/jor.23287.

    Google Scholar 

  32. Street J, Bao M, de Guzman L, Bunting S, Peale Jr FV, Ferrara N, Steinmetz H, Hoeffel J, Cleland JL, Daugherty A, van Bruggen N, Redmond HP, Carano RA, Filvaroff EH. Vascular endothelial growth factor stimulates bone repair by promoting angiogenesis and bone turnover. Proc Natl Acad Sci U S A. 2002;99(15):9656–61.

    Article  Google Scholar 

  33. Peng H, Usas A, Olshanski A, Ho AM, Gearhart B, Cooper GM, Huard J. VEGF improves, whereas sFlt1 inhibits, BMP2-induced bone formation and bone healing through modulation of angiogenesis. J Bone Miner Res. 2005;20(11):2017–27.

    Article  Google Scholar 

  34. Gerber HP, Vu TH, Ryan AM, Kowalski J, Werb Z, Ferrara N. VEGF couples hypertrophic cartilage remodeling, ossification and angiogenesis during endochondral bone formation. Nat Med. 1999;5(6):623.

    Article  Google Scholar 

  35. Patel ZS, Young S, Tabata Y, Jansen JA, Wong ME, Mikos AG. Dual delivery of an angiogenic and an osteogenic growth factor for bone regeneration in a critical size defect model. Bone. 2008;43(5):931–40.

    Article  Google Scholar 

  36. Shah NJ, Macdonald ML, Beben YM, Padera RF, Samuel RE, Hammond PT. Tunable dual growth factor delivery from polyelectrolyte multilayer films. Biomaterials. 2011;32:6183–93.

    Article  Google Scholar 

  37. Kempen DH, Lu L, Heijink A, Hefferan TE, Creemers LB, Maran A, Yaszemski MJ, Dhert WJ. Effect of local sequential VEGF and BMP-2 delivery on ectopic and orthotopic bone regeneration. Biomaterials. 2009;30(14):2816–25.

    Article  Google Scholar 

  38. Cui Q, Dighe AS, Irvine Jr JN. Combined angiogenic and osteogenic factor delivery for bone regenerative engineering. Curr Pharm Des. 2013;19(19):3374–83.

    Article  Google Scholar 

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Acknowledgements

This work was supported by the Army, Navy, NIH, Air Force, VA, and Health Affairs to support the AFIRM II effort, under award no. W81XWH-14-2-0003. The US Army Medical Research Acquisition Activity, 820 Chandler Street, Fort Detrick MD 21702-5014 is the awarding and administering acquisition office. Opinions, interpretations, conclusions, and recommendations are those of the author and are not necessarily endorsed by the Department of Defense.

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Authors and Affiliations

  1. Department of Biomedical Engineering, University of Connecticut, Storrs, CT, USA

    Fayekah Assanah, Casey McDermott, Seth Malinowski, Sangamesh Kumbar & Yusuf Khan

  2. Institute for Regenerative Engineering, UConn Health, MC3711, Room No: E7052 263 Farmington Avenue, Farmington, CT, 06030, USA

    Farzana Sharmin, Sangamesh Kumbar & Yusuf Khan

  3. Department of Orthopaedic Surgery, UConn Health, Farmington, CT, USA

    Sangamesh Kumbar, Douglas J. Adams & Yusuf Khan

  4. UConn Musculoskeletal Institute, Farmington, CT, USA

    Sangamesh Kumbar, Douglas J. Adams & Yusuf Khan

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  1. Fayekah Assanah
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  2. Casey McDermott
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Correspondence to Yusuf Khan.

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Assanah, F., McDermott, C., Malinowski, S. et al. Enhancing the Functionality of Trabecular Allografts Through Polymeric Coating for Factor Loading. Regen. Eng. Transl. Med. 3, 75–81 (2017). https://doi.org/10.1007/s40883-017-0027-x

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