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Current Modalities for Fracture Healing Enhancement

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Tissue Engineering and Regenerative Medicine Aims and scope

Abstract

Previously, most fractures have been treated through bone reduction and immobilization. With an increase in the patients’ need for an early return to their normal function, development in surgical techniques and materials have accelerated. However, delayed union or non-union of the fracture site sometimes inhibits immediate return to normal life. To enhance fracture healing, diverse materials and methods have been developed. This is a review on the current modalities of fracture healing enhancement, which aims to provide a comprehensive knowledge regarding fracture healing for researchers and health practitioners.

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References

  1. Bhatt RA, Rozental TD. Bone graft substitutes. Hand Clin. 2012;28:457–68.

    Article  PubMed  Google Scholar 

  2. Pape HC, Evans A, Kobbe P. Autologous bone graft: properties and techniques. J Orthop Trauma. 2010;24:S36–40.

    Article  PubMed  Google Scholar 

  3. Fernandez-Bances I, Perez-Basterrechea M, Perez-Lopez S, Nuñez Batalla D, Fernandez Rodriguez MA, Alvarez-Viejo M, et al. Repair of long-bone pseudoarthrosis with autologous bone marrow mononuclear cell combined with allogenic bone graft. Cytotherapy. 2013;15:571–7.

    Article  CAS  PubMed  Google Scholar 

  4. Baldwin P, Li DJ, Auston DA, Mir HS, Yoon RS, Koval KJ. Autograft, allograft, and bone graft substitutes: clinical evidence and indications for use in the setting of orthopaedic trauma surgery. J Orthop Trauma. 2019;33:203–13.

    Article  PubMed  Google Scholar 

  5. Masquelet AC. Muscle reconstruction in reconstructive surgery: soft tissue repair and long bone reconstruction. Langenbecks Arch Surg. 2003;388:344–6.

    Article  CAS  PubMed  Google Scholar 

  6. Wang J, Yin Q, Gu S, Wu Y, Rui Y. Induced membrane technique in the treatment of infectious bone defect: a clinical analysis. Orthop Traumatol Surg Res. 2019;105:535–9.

    Article  PubMed  Google Scholar 

  7. Brinker MR, O’Connor DP. Exchange nailing of ununited fractures. J Bone Joint Surg Am. 2007;89:177–88.

    Article  PubMed  Google Scholar 

  8. Calori GM, Colombo M, Mazza EL, Mazzola S, Malagoli E, Mineo GV. Incidence of donor site morbidity following harvesting from iliac crest or RIA graft. Injury. 2014;45:S116–20.

    Article  PubMed  Google Scholar 

  9. Chiarello E, Cadossi M, Tedesco G, Capra P, Calamelli C, Shehu A, et al. Autograft, allograft and bone substitutes in reconstructive orthopedic surgery. Aging Clin Exp Res. 2013;25:S101–3.

    Article  PubMed  Google Scholar 

  10. Sohn HS, Oh JK. Review of bone graft and bone substitutes with an emphasis on fracture surgeries. Biomater Res. 2019;23:9.

    Article  PubMed  PubMed Central  Google Scholar 

  11. Centers for Disease Control (CDC). Transmission of HIV through bone transplantation: case report and public health recommendations. MMWR Morb Mortal Wkly Rep. 1988;37:597–9.

  12. Zamborsky R, Svec A, Bohac M, Kilian M, Kokavec M. Infection in bone allograft transplants. Exp Clin Transplant. 2016;14:484–90.

    PubMed  Google Scholar 

  13. Aslantürk O, Akman YE, Öztürk H, Eltayeb MEM, Küçükkaya M, Hamzaoğlu A. “Sandwich technique” with dual strut allograft in surgical treatment of femoral nonunion. Injury. 2020;51:1057–61.

    Article  PubMed  Google Scholar 

  14. Ullmark G, Obrant KJ. Histology of impacted bone-graft incorporation. J Arthroplast. 2002;17:150–7.

    Article  CAS  Google Scholar 

  15. Garrison KR, Shemilt I, Donell S, Ryder JJ, Mugford M, Harvey I, et al. Bone morphogenetic protein (BMP) for fracture healing in adults. Cochrane Database Syst Rev. 2010;2010:CD006950.

    Google Scholar 

  16. Devescovi V, Leonardi E, Ciapetti G, Cenni E. Growth factors in bone repair. Chir Organi Mov. 2008;92:161–8.

    Article  PubMed  Google Scholar 

  17. Eckardt H, Ding M, Lind M, Hansen ES, Christensen KS, Hvid I. Recombinant human vascular endothelial growth factor enhances bone healing in an experimental nonunion model. J Bone Joint Surg Br. 2005;87:1434–8.

    Article  CAS  PubMed  Google Scholar 

  18. Kawaguchi H, Oka H, Jingushi S, Izumi T, Fukunaga M, Sato K, et al. A local application of recombinant human fibroblast growth factor 2 for tibial shaft fractures: a randomized, placebo-controlled trial. J Bone Miner Res. 2010;25:2735–43.

  19. Li M, Ke HZ, Qi H, Healy DR, Li Y, Crawford DT, et al. A novel, non-prostanoid ep2 receptor-selective prostaglandin e2 agonist stimulates local bone formation and enhances fracture healing. J Bone Miner Res. 2003;18:2033–42.

    Article  CAS  PubMed  Google Scholar 

  20. Feigenson M, Jonason JH, Shen J, Loiselle AE, Awad HA, O’Keefe RJ. Inhibition of the prostaglandin ep-1 receptor in periosteum progenitor cells enhances osteoblast differentiation and fracture repair. Ann Biomed Eng. 2020;48:927–39.

    Article  PubMed  Google Scholar 

  21. Zimmermann G, Moghaddam A. Allograft bone matrix versus synthetic bone graft substitutes. Injury. 2011;42:S16–21.

    Article  PubMed  Google Scholar 

  22. Oliveira HL, Da Rosa WLO, Cuevas-Suárez CE, Carreño NLV, da Silva AF, Guim TN, et al. Histological evaluation of bone repair with hydroxyapatite: a systematic review. Calcif Tissue Int. 2017;101:341–54.

    Article  CAS  PubMed  Google Scholar 

  23. Zhang H, Yang L, Yang XG, Wang F, Feng JT, Hua KC, et al. Demineralized bone matrix carriers and their clinical applications: an overview. Orthop Surg. 2019;11:725–37.

    Article  PubMed  PubMed Central  Google Scholar 

  24. Ho-Shui-Ling A, Bolander J, Rustom LE, Johnson AW, Luyten FP, Picart C. Bone regeneration strategies: engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials. 2018;180:143–62.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Šponer P, Kučera T, Brtková J, Urban K, Kočí Z, Měřička P, et al. Comparative study on the application of mesenchymal stromal cells combined with tricalcium phosphate scaffold into femoral bone defects. Cell Transplant. 2018;27:1459–68.

    Article  PubMed  PubMed Central  Google Scholar 

  26. Bohner M, Santoni BLG, Döbelin N. β-tricalcium phosphate for bone substitution: synthesis and properties. Acta Biomater. 2020;113:23–41.

    Article  CAS  PubMed  Google Scholar 

  27. Zwingenberger S, Nich C, Valladares RD, Yao Z, Stiehler M, Goodman SB. Recommendations and considerations for the use of biologics in orthopedic surgery. BioDrugs. 2012;26:245–56.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. DiGiovanni CW, Lin SS, Baumhauer JF, Daniels T, Younger A, Glazebrook M, et al. Recombinant human platelet-derived growth factor-BB and beta-tricalcium phosphate (rhPDGF-BB/β-TCP): an alternative to autogenous bone graft. J Bone Joint Surg Am. 2013;95:1184–92.

    Article  PubMed  Google Scholar 

  29. Kelly CM, Wilkins RM, Gitelis S, Hartjen C, Watson JT, Kim PT. The use of a surgical grade calcium sulfate as a bone graft substitute: results of a multicenter trial. Clin Orthop Relat Res. 2001;382:42–50.

    Article  Google Scholar 

  30. Fernandez de Grado G, Keller L, Idoux-Gillet Y, Wagner Q, Musset AM, Jessel-Benkirane N, et al. Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management. J Tissue Eng. 2018;9:2041731418776819.

  31. Hofmann A, Gorbulev S, Guehring T, Schulz AP, Schupfner R, Raschke M, et al. Autologous iliac bone graft compared with biphasic hydroxyapatite and calcium sulfate cement for the treatment of bone defects in tibial plateau fractures: a prospective, randomized, open-label, multicenter study. J Bone Joint Surg Am. 2020;102:179–93.

  32. Turner TM, Urban RM, Hall DJ, Infanger S, Gitelis S, Petersen DW, et al. Osseous healing using injectable calcium sulfate-based putty for the delivery of demineralized bone matrix and cancellous bone chips. Orthopedics. 2003;26:S571–5.

    Article  PubMed  Google Scholar 

  33. Hartshorne E. On the causes and treatment of pseudarthrosis and especially that form of it sometimes called supernumerary joint. Am J Med Sci. 1841;1:121–56.

    Article  Google Scholar 

  34. Einhorn, TA. Enhancement of fracture-healing. J Bone Joint Surg Am. 1995;77:940–56.

  35. Moretti B, Notarnicola A, Moretti L, Patella S, Tatò I, Patella V. Bone healing induced by ESWT. Clin Cases Miner Bone Metab. 2009;6:155–8.

    PubMed  PubMed Central  Google Scholar 

  36. Leal C, D’Agostino C, Gomez Garcia S, Fernandez A. Current concepts of shockwave therapy in stress fractures. Int J Surg. 2015;24:195–200.

    Article  PubMed  Google Scholar 

  37. Bara T, Synder M. Nine-years experience with the use of shock waves for treatment of bone union disturbances. Ortop Traumatol Rehabil. 2007;9:254–8.

    PubMed  Google Scholar 

  38. Chen YJ, Wurtz T, Wang CJ, Kuo YR, Yang KD, Huang HC, et al. Recruitment of mesenchymal stem cells and expression of TGF-beta 1 and VEGF in the early stage of shock wave-promoted bone regeneration of segmental defect in rats. J Orthop Res. 2004;22:526–34.

    Article  CAS  PubMed  Google Scholar 

  39. Rutten S, van den Bekerom MPJ, Sierevelt IN, Nolte PA. Enhancement of bone-healing by low-intensity pulsed ultrasound: a systematic review. JBJS Rev. 2016;4:e6.

    Article  Google Scholar 

  40. Kim KW, Ha KY, Moon MS, Kim YS, Kwon SY, Woo YK. Volumetric change of the graft bone after intertransverse fusion. Spine. 1999;24:428–33.

    Article  CAS  PubMed  Google Scholar 

  41. Kim SJ, Jang JD, Lee SK. Treatment of long tubular bone defect of rabbit using autologous cultured osteoblasts mixed with fibrin. Cytotechnology. 2007;54:115–20.

    Article  CAS  Google Scholar 

  42. Kim SJ, Shin YW, Yang KH, Kim SB, Yoo MJ, Han SK, et al. A multi-center, randomized, clinical study to compare the effect and safety of autologous cultured osteoblast (OssronTM) injection to treat fractures. BMC Musculoskelet Disord. 2009;10:20.

    Article  PubMed  PubMed Central  Google Scholar 

  43. Hong SH, Bahk WJ, Yang SJ, Kim KW, Kim SJ, Chang CH, et al. Osteogenecity and biomechanical properties of autologous osteoblast cells mixed with fibrin. Tissue Eng Regen Med. 2009;6:52–6.

    Google Scholar 

  44. Park HY, Shetty AA, Kim JM, Kim YJ, Jang JD, Choi NY, et al. Enhancement of healing of long tubular bone defects in rabbits using a mixture of atelocollagen gel and bone marrow aspirate concentrate. Cells Tissues Organs. 2017;203:339–52.

    Article  CAS  PubMed  Google Scholar 

  45. Kim SJ, Shettey AA. Stem cell research in orthopaedic and trauma surgery. In: Shetty AA, Kim SJ, Nakamura N, Brittberg M, editors. Techniques in cartilage repair surgery. Springer: Berlin, Heidelberg; 2014. p. 215–55.

  46. Braly HL, O’Connor DP, Brinker MR. Percutaneous autologous bone marrow injection in the treatment of distal meta-diaphyseal tibial nonunions and delayed unions. J Orthop Trauma. 2013;27:527–33.

    Article  PubMed  Google Scholar 

  47. 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;30:1–9.

    Article  PubMed  Google Scholar 

  48. Van Vugt TAG, Geurts JAP, Blokhuis TJ. Treatment of infected tibial non-unions using a BMAC and S53P4 BAG combination for reconstruction of segmental bone defects: A clinical case series. Injury. 2021;52:S67–71.

    Article  Google Scholar 

  49. Lin K, VandenBerg J, Putnam SM, Parks CD, Spraggs-Hughes A, McAndrew CM, et al. Bone marrow aspirate concentrate with cancellous allograft versus iliac crest bone graft in the treatment of long bone nonunions. OTA Int. 2019;2:e012.

    Article  Google Scholar 

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Correspondence to Seok Jung Kim.

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Chun, Y.S., Lee, D.H., Won, T.G. et al. Current Modalities for Fracture Healing Enhancement. Tissue Eng Regen Med 19, 11–17 (2022). https://doi.org/10.1007/s13770-021-00399-0

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  • DOI: https://doi.org/10.1007/s13770-021-00399-0

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