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Clinical Oral Investigations

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Open Access 01-04-2021 | Growth Factors | Original Article

Cellular responses to deproteinized bovine bone mineral biofunctionalized with bone-conditioned medium

Authors: Ludovica Parisi, Daniel Buser, Vivianne Chappuis, Maria B. Asparuhova

Published in: Clinical Oral Investigations | Issue 4/2021

Abstract

Objectives

The aim of the study was to investigate whether the osteoinductive properties of bone-conditioned medium (BCM) harvested from cortical bone chips within a clinically relevant short-term period can enhance the biologic characteristics of deproteinized bovine bone mineral (DBBM) in vitro.

Materials and methods

To assess the biofunctionalization of DBBM, the adhesive, proliferative, and differentiation properties of mesenchymal stromal ST2, pre-osteoblastic MC3T3-E1, and primary bone-derived cells grown on BCM-coated DBBM were examined by crystal violet staining of adherent cells, BrdU ELISA, and qRT-PCR, respectively.

Results

BCM extracted within 20 min or 24 h in either Ringer’s solution (BCM-RS) or RS mixed with autologous serum (BCM-RS + S) increased the adhesive properties of all three cell types seeded on DBBM. The 20-min BCM-RS preparation appeared more potent than the 24-h preparation. BCM-RS made within 20 min or 24 h had strong pro-proliferative effects on all cell types grown on DBBM. RS + S alone exhibited a considerable pro-proliferative effect, suggesting an impact of the serum on cellular growth. DBBM coated with BCM-RS or BCM-RS + S, made within 20 min or 24 h each, caused a significant induction of osteogenic differentiation marker expression with a higher potency of the BCM-RS + S. Finally, a strong additive effect of fresh bone chips combined with BCM-coated DBBM on the osteogenic differentiation of the three cell types was observed.

Conclusions

Altogether, the data strongly support the biofunctionalization of DBBM with BCM extracted within a clinically relevant time window of 20 min.

Clinical relevance

Pre-activation of non-osteoinductive biomaterials with BCM, prepared from autologous bone chips during a guided bone regeneration (GBR) procedure, bears the potential of an optimal treatment modality for bone defects in daily practice.

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Kao ST, Scott DD (2007) A review of bone substitutes. Oral Maxillofac Surg Clin North Am 19(4):513–521, vi. https://doi.org/10.1016/j.coms.2007.06.002CrossRefPubMed

Chiapasco M, Casentini P, Zaniboni M (2009) Bone augmentation procedures in implant dentistry. Int J Oral Maxillofac Implants 24:237–259PubMed

Buser D, Chappuis V, Kuchler U, Bornstein MM, Wittneben JG, Buser R, Cavusoglu Y, Belser UC (2013) Long-term stability of early implant placement with contour augmentation. J Dent Res 92(12 Suppl):176S–182S. https://doi.org/10.1177/0022034513504949CrossRefPubMedPubMedCentral

Campana V, Milano G, Pagano E, Barba M, Cicione C, Salonna G, Lattanzi W, Logroscino G (2014) Bone substitutes in orthopaedic surgery: from basic science to clinical practice. J Mater Sci Mater Med 25(10):2445–2461. https://doi.org/10.1007/s10856-014-5240-2CrossRefPubMedPubMedCentral

Stern A, Barzani G (2015) Autogenous bone harvest for implant reconstruction. Dent Clin N Am 59(2):409–420. https://doi.org/10.1016/j.cden.2014.10.011CrossRefPubMed

Caballé-Serrano J, Bosshardt DD, Buser D, Gruber R (2014) Proteomic analysis of porcine bone-conditioned medium. Int J Oral Maxillofac Implants 29(5):1208–1215dCrossRef

Filho GS, Caballé-Serrano J, Sawada K, Bosshardt DD, Bianchini MA, Buser D, Gruber R (2015) Conditioned medium of demineralized freeze-dried bone activates gene expression in periodontal fibroblasts in vitro. J Periodontol 86(6):827–834. https://doi.org/10.1902/jop.2015.140676CrossRefPubMed

Zimmermann M, Caballé-Serrano J, Bosshardt D, Ankersmit H, Buser D, Gruber R (2015) Bone-conditioned medium changes gene expression in bone-derived fibroblasts. Int J Oral Maxillofac Implants 30(4):953–958CrossRef

Caballé-Serrano J, Filho GS, Bosshardt DD, Gargallo-Albiol J, Buser D, Gruber R (2016) Conditioned medium from fresh and demineralized bone enhances osteoclastogenesis in murine bone marrow cultures. Clin Oral Implants Res 27(2):226–232. https://doi.org/10.1111/clr.12573CrossRefPubMed

10.

Hallman M, Lundgren S, Sennerby L (2001) Histologic analysis of clinical biopsies taken 6 months and 3 years after maxillary sinus floor augmentation with 80% bovine hydroxyapatite and 20% autogenous bone mixed with fibrin glue. Clin Implant Dent Relat Res 3(2):87–96. https://doi.org/10.1111/j.1708-8208.2001.tb00236.xCrossRefPubMed

11.

Nkenke E, Radespiel-Tröger M, Wiltfang J, Schultze-Mosgau S, Winkler G, Neukam FW (2002) Morbidity of harvesting of retromolar bone grafts: a prospective study. Clin Oral Implants Res 13(5):514–521. https://doi.org/10.1034/j.1600-0501.2002.130511.xCrossRefPubMed

12.

Cricchio G, Lundgren S (2003) Donor site morbidity in two different approaches to anterior iliac crest bone harvesting. Clin Implant Dent Relat Res 5(3):161–169. https://doi.org/10.1111/j.1708-8208.2003.tb00198.xCrossRefPubMed

13.

Dahlin C, Linde A, Gottlow J, Nyman S (1988) Healing of bone defects by guided tissue regeneration. Plast Reconstr Surg 81(5):672–676. https://doi.org/10.1097/00006534-198805000-00004CrossRefPubMed

14.

Dahlin C, Gottlow J, Linde A, Nyman S (1990) Healing of maxillary and mandibular bone defects using a membrane technique. An experimental study in monkeys. Scand J Plast Reconstr Surg Hand Surg 24(1):13–19. https://doi.org/10.3109/02844319009004514CrossRefPubMed

15.

Schenk RK, Buser D, Hardwick WR, Dahlin C (1994) Healing pattern of bone regeneration in membrane-protected defects: a histologic study in the canine mandible. Int J Oral Maxillofac Implants 9(1):13–29PubMed

16.

Buser D, Chen ST, Weber HP, Belser UC (2008) Early implant placement following single-tooth extraction in the esthetic zone: biologic rationale and surgical procedures. Int J Periodontics Restorative Dent 28(5):441–451PubMed

17.

Buser D, Chappuis V, Bornstein MM, Wittneben J-G, Frei M, Belser UC (2013) Long-term stability of contour augmentation with early implant placement following single tooth extraction in the esthetic zone: a prospective, cross-sectional study in 41 patients with a 5- to 9-year follow-up. J Periodontol 84(11):1517–1527. https://doi.org/10.1902/jop.2013.120635CrossRefPubMed

18.

Jensen SS, Bosshardt DD, Gruber R, Buser D (2014) Long-term stability of contour augmentation in the esthetic zone: histologic and histomorphometric evaluation of 12 human biopsies 14 to 80 months after augmentation. J Periodontol 85(11):1549–1556. https://doi.org/10.1902/jop.2014.140182CrossRefPubMed

19.

Urban IA, Nagursky H, Lozada JL, Nagy K (2013) Horizontal ridge augmentation with a collagen membrane and a combination of particulated autogenous bone and anorganic bovine bone-derived mineral: a prospective case series in 25 patients. Int J Periodontics Restorative Dent 33(3):299–307. https://doi.org/10.11607/prd.1407CrossRefPubMed

20.

Urban IA, Lozada JL, Jovanovic SA, Nagursky H, Nagy K (2014) Vertical ridge augmentation with titanium-reinforced, dense-PTFE membranes and a combination of particulated autogenous bone and anorganic bovine bone-derived mineral: a prospective case series in 19 patients. Int J Oral Maxillofac Implants 29(1):185–193. https://doi.org/10.11607/jomi.3346CrossRefPubMed

21.

Bornstein MM, Chappuis V, Von Arx T, Buser D (2008) Performance of dental implants after staged sinus floor elevation procedures: 5-year results of a prospective study in partially edentulous patients. Clin Oral Implants Res 19(10):1034–1043. https://doi.org/10.1111/j.1600-0501.2008.01573.xCrossRefPubMed

22.

Jensen SS, Bornstein MM, Dard M, Bosshardt DD, Buser D (2009) Comparative study of biphasic calcium phosphates with different HA/TCP ratios in mandibular bone defects. A long-term histomorphometric study in minipigs. J Biomed Mater Res B Appl Biomater 90B(1):171–181. https://doi.org/10.1002/jbm.b.31271CrossRef

23.

Klinge B, Alberius P, Isaksson S, Jönsson J (1992) Osseous response to implanted natural bone mineral and synthetic hydroxylapatite ceramic in the repair of experimental skull bone defects. J Oral Maxillofac Surg 50(3):241–249. https://doi.org/10.1016/0278-2391(92)90320-yCrossRefPubMed

24.

Cordaro L, Bosshardt DD, Palattella P, Rao W, Serino G, Chiapasco M (2008) Maxillary sinus grafting with Bio-Oss or Straumann Bone Ceramic: histomorphometric results from a randomized controlled multicenter clinical trial. Clin Oral Implants Res 19(8):796–803. https://doi.org/10.1111/j.1600-0501.2008.01565.xCrossRefPubMed

25.

Cohen RE, Mullarky RH, Noble B, Comeau RL, Neiders ME (1994) Phenotypic characterization of mononuclear cells following anorganic bovine bone implantation in rats. J Periodontol 65(11):1008–1015. https://doi.org/10.1902/jop.1994.65.11.1008CrossRefPubMed

26.

Yildirim M, Spiekermann H, Biesterfeld S, Edelhoff D (2000) Maxillary sinus augmentation using xenogenic bone substitute material Bio-Oss in combination with venous blood. A histologic and histomorphometric study in humans. Clin Oral Implants Res 11(3):217–229. https://doi.org/10.1034/j.1600-0501.2000.011003217.xCrossRefPubMed

27.

Caballé-Serrano J, Fujioka-Kobayashi M, Bosshardt DD, Gruber R, Buser D, Miron RJ (2016) Pre-coating deproteinized bovine bone mineral (DBBM) with bone-conditioned medium (BCM) improves osteoblast migration, adhesion, and differentiation in vitro. Clin Oral Investig 20(9):2507–2513. https://doi.org/10.1007/s00784-016-1747-xCrossRefPubMed

28.

Caballé-Serrano J, Sawada K, Miron RJ, Bosshardt DD, Buser D, Gruber R (2017) Collagen barrier membranes adsorb growth factors liberated from autogenous bone chips. Clin Oral Implants Res 28(2):236–241. https://doi.org/10.1111/clr.12789CrossRefPubMed

29.

Kuchler U, Rybaczek T, Dobask T, Heimel P, Tangl S, Klehm J, Menzel M, Gruber R (2018) Bone-conditioned medium modulates the osteoconductive properties of collagen membranes in a rat calvaria defect model. Clin Oral Implants Res 29(4):381–388. https://doi.org/10.1111/clr.13133CrossRefPubMed

30.

Caballé-Serrano J, Sawada K, Filho GS, Bosshardt DD, Buser D, Gruber R (2015) Bone conditioned medium: preparation and bioassay. J Vis Exp 101:e52707. https://doi.org/10.3791/52707CrossRef

31.

Peng J, Nemec M, Brolese E, Bosshardt DD, Schaller B, Buser D, Gruber R (2015) Bone-conditioned medium inhibits osteogenic and adipogenic differentiation of mesenchymal cells in vitro. Clin Implant Dent Relat Res 17(5):938–949. https://doi.org/10.1111/cid.12200CrossRefPubMed

32.

Brolese E, Buser D, Kuchler U, Schaller B, Gruber R (2015) Human bone chips release of sclerostin and FGF-23 into the culture medium: an in vitro pilot study. Clin Oral Implants Res 26(10):1211–1214. https://doi.org/10.1111/clr.12432CrossRefPubMed

33.

Asparuhova MB, Caballé-Serrano J, Buser D, Chappuis V (2018) Bone-conditioned medium contributes to initiation and progression of osteogenesis by exhibiting synergistic TGF-β1/BMP-2 activity. Int J Oral Sci 10(2):20. https://doi.org/10.1038/s41368-018-0021-2CrossRefPubMedPubMedCentral

34.

Miron RJ, Gruber R, Hedbom E, Saulacic N, Zhang Y, Sculean A, Bosshardt DD, Buser D (2013) Impact of bone harvesting techniques on cell viability and the release of growth factors of autografts. Clin Implant Dent Relat Res 15(4):481–489. https://doi.org/10.1111/j.1708-8208.2012.00440.xCrossRefPubMed

35.

Miron RJ, Hedbom E, Saulacic N, Zhang Y, Sculean A, Bosshardt DD, Buser D (2011) Osteogenic potential of autogenous bone grafts harvested with four different surgical techniques. J Dent Res 90(12):1428–1433. https://doi.org/10.1177/0022034511422718CrossRefPubMed

36.

Saulacic N, Bosshardt DD, Jensen SS, Miron RJ, Gruber R, Buser D (2015) Impact of bone graft harvesting techniques on bone formation and graft resorption: a histomorphometric study in the mandibles of minipigs. Clin Oral Implants Res 26(4):383–391. https://doi.org/10.1111/clr.12357CrossRefPubMed

37.

Bakker AD, Klein-Nulend J (2012) Osteoblast isolation from murine calvaria and long bones. Methods Mol Biol 816:19–29. https://doi.org/10.1007/978-1-61779-415-5_2CrossRefPubMed

38.

Bonewald LF (2011) The amazing osteocyte. J Bone Miner Res 26(2):229–238. https://doi.org/10.1002/jbmr.320CrossRefPubMed

39.

Capulli M, Paone R, Rucci N (2014) Osteoblast and osteocyte: games without frontiers. Arch Biochem Biophys 561:3–12. https://doi.org/10.1016/j.abb.2014.05.003CrossRefPubMed

40.

Gurbuz I, Ferralli J, Roloff T, Chiquet-Ehrismann R, Asparuhova MB (2014) SAP domain-dependent Mkl1 signaling stimulates proliferation and cell migration by induction of a distinct gene set indicative of poor prognosis in breast cancer patients. Mol Cancer 13:22–22. https://doi.org/10.1186/1476-4598-13-22CrossRefPubMedPubMedCentral

41.

Livak KJ, Schmittgen TD (2001) Analysis of relative gene expression data using real-time quantitative PCR and the 2(-Delta Delta C(T)) method. Methods 25(4):402–408CrossRef

42.

Von Arx T, Buser D (2006) Horizontal ridge augmentation using autogenous block grafts and the guided bone regeneration technique with collagen membranes: a clinical study with 42 patients. Clin Oral Implants Res 17(4):359–366. https://doi.org/10.1111/j.1600-0501.2005.01234.xCrossRef

43.

Mardas N, Chadha V, Donos N (2010) Alveolar ridge preservation with guided bone regeneration and a synthetic bone substitute or a bovine-derived xenograft: a randomized, controlled clinical trial. Clin Oral Implants Res 21(7):688–698. https://doi.org/10.1111/j.1600-0501.2010.01918.xCrossRefPubMed

44.

Lindgren C, Mordenfeld A, Hallman M (2012) A prospective 1-year clinical and radiographic study of implants placed after maxillary sinus floor augmentation with synthetic biphasic calcium phosphate or deproteinized bovine bone. Clin Implant Dent Relat Res 14(1):41–50. https://doi.org/10.1111/j.1708-8208.2010.00224.xCrossRefPubMed

45.

Schmitt CM, Doering H, Schmidt T, Lutz R, Neukam FW, Schlegel KA (2013) Histological results after maxillary sinus augmentation with Straumann® BoneCeramic, Bio-Oss®, Puros®, and autologous bone. A randomized controlled clinical trial. Clin Oral Implants Res 24(5):576–585. https://doi.org/10.1111/j.1600-0501.2012.02431.xCrossRefPubMed

46.

Rosen VB, Hobbs LW, Spector M (2002) The ultrastructure of anorganic bovine bone and selected synthetic hyroxyapatites used as bone graft substitute materials. Biomaterials 23(3):921–928. https://doi.org/10.1016/s0142-9612(01)00204-6CrossRefPubMed

47.

Amaral M, Lopes MA, Silva RF, Santos JD (2002) Densification route and mechanical properties of Si3N4–bioglass biocomposites. Biomaterials 23(3):857–862. https://doi.org/10.1016/S0142-9612(01)00194-6CrossRefPubMed

48.

Liang L, Rulis P, Ching WY (2010) Mechanical properties, electronic structure and bonding of α- and β-tricalcium phosphates with surface characterization. Acta Biomater 6(9):3763–3771. https://doi.org/10.1016/j.actbio.2010.03.033CrossRefPubMed

49.

Araújo MG, Carmagnola D, Berglundh T, Thilander B, Lindhe J (2001) Orthodontic movement in bone defects augmented with Bio-Oss. An experimental study in dogs. J Clin Periodontol 28(1):73–80. https://doi.org/10.1034/j.1600-051x.2001.280111.xCrossRefPubMed

50.

Baldini N, De Sanctis M, Ferrari M (2011) Deproteinized bovine bone in periodontal and implant surgery. Dent Mater 27(1):61–70. https://doi.org/10.1016/j.dental.2010.10.017CrossRefPubMed

51.

Hassan KS, Marei HF, Alagl AS (2011) Composite bone graft for treatment of osseous defects after surgical removal of impacted third and second molars: case report and review of the literature. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 112(6):e8–e15. https://doi.org/10.1016/j.tripleo.2011.04.010CrossRefPubMed

52.

Jensen T, Schou S, Stavropoulos A, Terheyden H, Holmstrup P (2012) Maxillary sinus floor augmentation with Bio-Oss or Bio-Oss mixed with autogenous bone as graft in animals: a systematic review. Int J Oral Maxillofac Surg 41(1):114–120. https://doi.org/10.1016/j.ijom.2011.08.010CrossRefPubMed

53.

Thoma DS, Kruse A, Ghayor C, Jung RE, Weber FE (2015) Bone augmentation using a synthetic hydroxyapatite/silica oxide-based and a xenogenic hydroxyapatite-based bone substitute materials with and without recombinant human bone morphogenetic protein-2. Clin Oral Implants Res 26(5):592–598. https://doi.org/10.1111/clr.12469CrossRefPubMed

54.

Miron RJ, Bosshardt DD, Buser D, Zhang Y, Tugulu S, Gemperli A, Dard M, Caluseru OM, Chandad F, Sculean A (2015) Comparison of the capacity of enamel matrix derivative gel and enamel matrix derivative in liquid formulation to adsorb to bone grafting materials. J Periodontol 86(4):578–587. https://doi.org/10.1902/jop.2015.140538CrossRefPubMed

55.

Ocak H, Kutuk N, Demetoglu U, Balcıoglu E, Ozdamar S, Alkan A (2017) Comparison of bovine bone-autogenic bone mixture versus platelet-rich fibrin for maxillary sinus grafting: histologic and histomorphologic study. J Oral Implantol 43(3):194–201. https://doi.org/10.1563/aaid-joi-D-16-00104CrossRefPubMed

56.

Kumar YR, Mohanty S, Verma M, Kaur RR, Bhatia P, Kumar VR, Chaudhary Z (2016) Platelet-rich fibrin: the benefits. Br J Oral Maxillofac Surg 54(1):57–61. https://doi.org/10.1016/j.bjoms.2015.10.015CrossRefPubMed

57.

Joseph VR, Sam G, Amol NV (2014) Clinical evaluation of autologous platelet rich fibrin in horizontal alveolar bony defects. J Clin Diagn Res 8(11):Zc43–Zc47. https://doi.org/10.7860/jcdr/2014/9948.5129CrossRef

58.

Dutta SR, Passi D, Singh P, Sharma S, Singh M, Srivastava D (2016) A randomized comparative prospective study of platelet-rich plasma, platelet-rich fibrin, and hydroxyapatite as a graft material for mandibular third molar extraction socket healing. Natl J Maxillofac Surg 7(1):45–51. https://doi.org/10.4103/0975-5950.196124CrossRefPubMedPubMedCentral

59.

Teti A (2011) Bone development: overview of bone cells and signaling. Curr Osteoporos Rep 9(4):264–273. https://doi.org/10.1007/s11914-011-0078-8CrossRefPubMed

60.

Himmlova L, Kubies D, Hulejova H, Bartova J, Riedel T, Stikarova J, Suttnar J, Pesakova V (2016) Effect of blood component coatings of enosseal implants on proliferation and synthetic activity of human osteoblasts and cytokine production of peripheral blood mononuclear cells. Mediat Inflamm 2016:8769347–8769315. https://doi.org/10.1155/2016/8769347CrossRef

61.

Terheyden H, Jepsen S, Möller B, Tucker MM, Rueger DC (1999) Sinus floor augmentation with simultaneous placement of dental implants using a combination of deproteinized bone xenografts and recombinant human osteogenic protein-1. A histometric study in miniature pigs. Clin Oral Implants Res 10(6):510–521. https://doi.org/10.1034/j.1600-0501.1999.100609.xCrossRefPubMed

62.

Jung RE, Glauser R, Schärer P, Hämmerle CH, Sailer HF, Weber FE (2003) Effect of rhBMP-2 on guided bone regeneration in humans. Clin Oral Implants Res 14(5):556–568. https://doi.org/10.1034/j.1600-0501.2003.00921.xCrossRefPubMed

63.

Nevins M, Camelo M, Nevins ML, Schenk RK, Lynch SE (2003) Periodontal regeneration in humans using recombinant human platelet-derived growth factor-BB (rhPDGF-BB) and allogenic bone. J Periodontol 74(9):1282–1292. https://doi.org/10.1902/jop.2003.74.9.1282CrossRefPubMed

64.

Gruber RM, Ludwig A, Merten H-A, Achilles M, Poehling S, Schliephake H (2008) Sinus floor augmentation with recombinant human growth and differentiation factor-5 (rhGDF-5): a histological and histomorphometric study in the Goettingen miniature pig. Clin Oral Implants Res 19(5):522–529. https://doi.org/10.1111/j.1600-0501.2007.01494.xCrossRefPubMed

65.

Schwarz F, Rothamel D, Herten M, Ferrari D, Sager M, Becker J (2008) Lateral ridge augmentation using particulated or block bone substitutes biocoated with rhGDF-5 and rhBMP-2: an immunohistochemical study in dogs. Clin Oral Implants Res 19(7):642–652. https://doi.org/10.1111/j.1600-0501.2008.01537.xCrossRefPubMed

66.

Kitamura M, Akamatsu M, Machigashira M, Hara Y, Sakagami R, Hirofuji T, Hamachi T, Maeda K, Yokota M, Kido J, Nagata T, Kurihara H, Takashiba S, Sibutani T, Fukuda M, Noguchi T, Yamazaki K, Yoshie H, Ioroi K, Arai T, Nakagawa T, Ito K, Oda S, Izumi Y, Ogata Y, Yamada S, Shimauchi H, Kunimatsu K, Kawanami M, Fujii T, Furuichi Y, Furuuchi T, Sasano T, Imai E, Omae M, Yamada S, Watanuki M, Murakami S (2011) FGF-2 stimulates periodontal regeneration: results of a multi-center randomized clinical trial. J Dent Res 90(1):35–40. https://doi.org/10.1177/0022034510384616CrossRefPubMed

67.

Emerton KB, Drapeau SJ, Prasad H, Rohrer M, Roffe P, Hopper K, Schoolfield J, Jones A, Cochran DL (2011) Regeneration of periodontal tissues in non-human primates with rhGDF-5 and beta-tricalcium phosphate. J Dent Res 90(12):1416–1421. https://doi.org/10.1177/0022034511423665CrossRefPubMed

68.

Bowen-Pope DF, Malpass TW, Foster DM, Ross R (1984) Platelet-derived growth factor in vivo: levels, activity, and rate of clearance. Blood 64(2):458–469CrossRef

69.

Anusaksathien O, Giannobile WV (2002) Growth factor delivery to re-engineer periodontal tissues. Curr Pharm Biotechnol 3(2):129–139. https://doi.org/10.2174/1389201023378391CrossRefPubMed

70.

Carreira AC, Lojudice FH, Halcsik E, Navarro RD, Sogayar MC, Granjeiro JM (2014) Bone morphogenetic proteins: facts, challenges, and future perspectives. J Dent Res 93(4):335–345. https://doi.org/10.1177/0022034513518561CrossRefPubMed

71.

Rocque BG, Kelly MP, Miller JH, Li Y, Anderson PA (2014) Bone morphogenetic protein-associated complications in pediatric spinal fusion in the early postoperative period: an analysis of 4658 patients and review of the literature. J Neurosurg Pediatr 14(6):635–643. https://doi.org/10.3171/2014.8.Peds13665CrossRefPubMed

Title: Cellular responses to deproteinized bovine bone mineral biofunctionalized with bone-conditioned medium
Authors: Ludovica Parisi
Daniel Buser
Vivianne Chappuis
Maria B. Asparuhova
Publication date: 01-04-2021
Publisher: Springer Berlin Heidelberg
Keywords: Growth Factors
Growth Factors
Published in: Clinical Oral Investigations / Issue 4/2021
Print ISSN: 1432-6981
Electronic ISSN: 1436-3771
DOI: https://doi.org/10.1007/s00784-020-03528-6

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Cellular responses to deproteinized bovine bone mineral biofunctionalized with bone-conditioned medium

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Objectives

Materials and methods

Results

Conclusions

Clinical relevance

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