Research progress of <i>in vivo</i> bioreactor for bone tissue engineering_Chinese Journal of Reparative and Reconstructive Surgery

Authors：

WANG Jian ^1,2 , WANG Xiao ³ , ZHEN Ping ² ,  FAN Bo ²

1. First School of Clinical Medicine, Gansu University of Chinese Medicine, Lanzhou Gansu, 730000, P.R.China;
2. Orthopaedic Center, the 940th Hospital of PLA Joint Logistics Support Force, Lanzhou Gansu, 730000, P.R.China;
3. School of Design and Art, Lanzhou University of Technology, Lanzhou Gansu, 730000, P.R.China;

Corresponding author：

FAN Bo, Email: fanbogk@163.com

Keywords：

In vivo bioreactor; bone tissue engineering; vascularization; prefabrication

DOI：

10.7507/1002-1892.202012083

Video：

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Objective To review the research progress of in vivo bioreactor (IVB) for bone tissue engineering in order to provide reference for its future research direction.Methods The literature related to IVB used in bone tissue engineering in recent years was reviewed, and the principles of IVB construction, tissue types, sites, and methods of IVB construction, as well as the advantages of IVB used in bone tissue engineering were summarized.Results IVB takes advantage of the body’s ability to regenerate itself, using the body as a bioreactor to regenerate new tissues or organs at injured sites or at ectopic sites that can support the regeneration of new tissues. IVB can be constructed by tissue flap (subcutaneous pocket, muscle flap/pocket, fascia flap, periosteum flap, omentum flap/abdominal cavity) and axial vascular pedicle (axial vascular bundle, arteriovenous loop) alone or jointly. IVB is used to prefabricate vascularized tissue engineered bone that matched the shape and size of the defect. The prefabricated vascularized tissue engineered bone can be used as bone graft, pedicled bone flap, or free bone flap to repair bone defect. IVB solves the problem of insufficient vascularization in traditional bone tissue engineering to a certain extent.Conclusion IVB is a promising method for vascularized tissue engineered bone prefabrication and subsequent bone defect reconstruction, with unique advantages in the repair of large complex bone defects. However, the complexity of IVB construction and surgical complications hinder the clinical application of IVB. Researchers should aim to develop a simple, safe, and efficient IVB.

Citation： WANG Jian, WANG Xiao, ZHEN Ping, FAN Bo. Research progress of in vivo bioreactor for bone tissue engineering. Chinese Journal of Reparative and Reconstructive Surgery, 2021, 35(5): 627-635. doi: 10.7507/1002-1892.202012083 Copy

1.	Stevens MM, Marini RP, Schaefer D, et al. In vivo engineering of organs: the bone bioreactor. Proc Natl Acad Sci U S A, 2005, 102(32): 11450-11455.
2.	Holt GE, Halpern JL, Dovan TT, et al. Evolution of an in vivo bioreactor. J Orthop Res, 2005, 23(4): 916-923.
3.	Wang Z, Han L, Sun T, et al. Construction of tissue-engineered bone with differentiated osteoblasts from adipose-derived stem cell and coral scaffolds at an ectopic site. Br J Oral Maxillofac Surg, 2021, 59(1): 46-51.
4.	Ma J, Yang F, Both SK, et al. Bone forming capacity of cell- and growth factor-based constructs at different ectopic implantation sites. J Biomed Mater Res A, 2015, 103(2): 439-450.
5.	Sharma S, Sapkota D, Xue Y, et al. Delivery of VEGFA in bone marrow stromal cells seeded in copolymer scaffold enhances angiogenesis, but is inadequate for osteogenesis as compared with the dual delivery of VEGFA and BMP2 in a subcutaneous mouse model. Stem Cell Res Ther, 2018, 9(1): 23.
6.	Wu H, Kang N, Wang Q, et al. The dose-effect relationship between the seeding quantity of human marrow mesenchymal stem cells and in vivo tissue-engineered bone yield. Cell transplantation, 2015, 24(10): 1957-1968.
7.	Drouin G, Couture V, Lauzon MA, et al. Muscle injury-induced hypoxia alters the proliferation and differentiation potentials of muscle resident stromal cells. Skeletal muscle, 2019, 9(1): 18.
8.	Molligan J, Mitchell R, Schon L, et al. Influence of bone and muscle injuries on the osteogenic potential of muscle progenitors: contribution of tissue environment to heterotopic ossification. Stem Cells Transl Med, 2016, 5(6): 745-753.
9.	Zhou M, Peng X, Mao C, et al. The value of SPECT/CT in monitoring prefabricated tissue-engineered bone and orthotopic rhBMP-2 implants for mandibular reconstruction. PLoS One, 2015, 10(9): e0137167.
10.	Khouri RK, Koudsi B, Reddi H. Tissue transformation into bone in vivo. A potential practical application. JAMA, 1991, 266(14): 1953-1955.
11.	Mesimäki K, Lindroos B, Törnwall J, et al. Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg, 2009, 38(3): 201-209.
12.	Kokemueller H, Spalthoff S, Nolff M, et al. Prefabrication of vascularized bioartificial bone grafts in vivo for segmental mandibular reconstruction: experimental pilot study in sheep and first clinical application. Int J Oral Maxillofac Surg, 2010, 39(4): 379-387.
13.	Zimmerer RM, Jehn P, Kokemüller H, et al. In vivo tissue engineered bone versus autologous bone: stability and structure. Int J Oral Maxillofac Surg, 2017, 46(3): 385-393.
14.	Zhou M, Peng X, Mao C, et al. Primate mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 implanted in situ. Biomaterials, 2010, 31(18): 4935-4943.
15.	Beck-Broichsitter BE, Becker ST, Seitz H, et al. Endocultivation: Histomorphological effects of repetitive rhBMP-2 application into prefabricated hydroxyapatite scaffolds at extraskeletal sites. J Craniomaxillofac Surg, 2015, 43(6): 981-988.
16.	Beck-Broichsitter BE, Becker ST, Seitz H, et al. Endocultivation: continuous application of rhBMP-2 via mini-osmotic pumps to induce bone formation at extraskeletal sites. Int J Oral Maxillofac Surg, 2017, 46(5): 655-661.
17.	张迅, 周立, 侯建玺, 等. 局部缓释VEGF对兔同种异体骨异位预构骨皮瓣的影响. 中华显微外科杂志, 2016, 39(6): 574-577.
18.	Ichikawa K, Ohta Y, Mamoto K, et al. Local co-application of zoledronate promotes long-term maintenance of newly formed bone induced by recombinant human bone morphogenetic protein 2. Biochem Biophys Res Commun, 2016, 480(3): 314-320.
19.	Tsagarakis M, Spyropoulou GA, Lykoudis E, et al. The use of vascularized fascia as carrier in cases of prelaminated fasciocartilaginous and osseofascial flaps. J Reconstr Microsurg, 2016, 32(4): 301-308.
20.	Aliyev A, Ekin Ö, Bitik O, et al. A novel method of neo-osseous flap prefabrication: induction of free calvarial periosteum with bioactive glass. J Reconstr Microsurg, 2018, 34(5): 307-314.
21.	Leonhardt H, Pradel W, Mai R, et al. Prefabricated bony radial forearm flap for secondary mandible reconstruction after radiochemotherapy. Head Neck, 2009, 31(12): 1579-1587.
22.	Sadigh PL, Jeng SF. Prelamination of the anterolateral thigh flap with a fibula graft to successfully reconstruct a mandibular defect. Plast Reconstr Surg Glob Open, 2015, 3(8): e497.
23.	Dou H, Wang G, Xing N, et al. Repair of large segmental bone defects with fascial flap-wrapped allogeneic bone. J Orthop Surg Res, 2016, 11(1): 162.
24.	Fan H, Zeng X, Wang X, et al. Efficacy of prevascularization for segmental bone defect repair using β-tricalcium phosphate scaffold in rhesus monkey. Biomaterials, 2014, 35(26): 7407-7415.
25.	Roberts SJ, van Gastel N, Carmeliet G, et al. Uncovering the periosteum for skeletal regeneration: the stem cell that lies beneath. Bone, 2015, 70: 10-18.
26.	Zhang H, Mao X, Zhao D, et al. Three dimensional printed polylactic acid-hydroxyapatite composite scaffolds for prefabricating vascularized tissue engineered bone: An in vivo bioreactor model. Sci Rep, 2017, 7(1): 15255.
27.	Huang RL, Tremp M, Ho CK, et al. Prefabrication of a functional bone graft with a pedicled periosteal flap as an in vivo bioreactor. Sci Rep, 2017, 7(1): 18038.
28.	Nau C, Henrich D, Seebach C, et al. Treatment of large bone defects with a vascularized periosteal flap in combination with biodegradable scaffold seeded with bone marrow-derived mononuclear cells: An experimental study in rats. Tissue Eng Part A, 2016, 22(1-2): 133-141.
29.	Nau C, Henrich D, Seebach C, et al. Tissue engineered vascularized periosteal flap enriched with MSC/EPCs for the treatment of large bone defects in rats. Int J Mol Med, 2017, 39(4): 907-917.
30.	Gallardo-Calero I, Barrera-Ochoa S, Manzanares MC, et al. Vascularized periosteal flaps accelerate osteointegration and revascularization of allografts in rats. Clin Orthop Relat Res, 2019, 477(4): 741-755.
31.	Tatara AM, Kretlow JD, Spicer PP, et al. Autologously generated tissue-engineered bone flaps for reconstruction of large mandibular defects in an ovine model. Tissue Eng Part A, 2015, 21(9-10): 1520-1528.
32.	Tatara AM, Shah SR, Demian N, et al. Reconstruction of large mandibular defects using autologous tissues generated from in vivo bioreactors. Acta Biomater, 2016, 45: 72-84.
33.	Tatara AM, Koons GL, Watson E, et al. Biomaterials-aided mandibular reconstruction using in vivo bioreactors. Proc Natl Acad Sci U S A, 2019, 116(14): 6954-6963.
34.	Watson E, Smith BT, Smoak MM, et al. Localized mandibular infection affects remote in vivo bioreactor bone generation. Biomaterials, 2020, 256: 120185.
35.	Wei J, Herrler T, Dai C, et al. Guided self-generation of vascularized neo-bone for autologous reconstruction of large mandibular defects. J Craniofac Surg, 2016, 27(4): 958-962.
36.	Zhao D, Jiang W, Wang Y, et al. Three-dimensional-printed poly-L-lactic acid scaffolds with different pore sizes influence periosteal distraction osteogenesis of a rabbit skull. Biomed Res Int, 2020, 2020: 7381391.
37.	Naujokat H, Açil Y, Harder S, et al. Osseointegration of dental implants in ectopic engineered bone in three different scaffold materials. Int J Oral Maxillofac Surg, 2020, 49(1): 135-142.
38.	Li J, Zhi W, Xu T, et al. Ectopic osteogenesis and angiogenesis regulated by porous architecture of hydroxyapatite scaffolds with similar interconnecting structure in vivo. Regen Biomater, 2016, 3(5): 285-297.
39.	Wiltfang J, Rohnen M, Egberts JH, et al. Man as a living bioreactor: Prefabrication of a custom vascularized bone graft in the gastrocolic omentum. Tissue Eng Part C Methods, 2016, 22(8): 740-746.
40.	Naujokat H, Açil Y, Gülses A, et al. Man as a living bioreactor: Long-term histological aspects of a mandibular replacement engineered in the patient’s own body. Int J Oral Maxillofac Surg, 2018, 47(11): 1481-1487.
41.	Birkenfeld F, Sengebusch A, Völschow C, et al. Endocultivation of scaffolds with recombinant human bone morphogenetic protein-2 and VEGF₁₆₅ in the omentum majus in a rabbit model. Tissue Eng Part C Methods, 2017, 23(12): 842-849.
42.	Birkenfeld F, Sengebusch A, Völschow C, et al. Scaffold implantation in the omentum majus of rabbits for new bone formation. J Craniomaxillofac Surg, 2019, 47(8): 1274-1279.
43.	Naujokat H, Lipp M, Açil Y, et al. Bone tissue engineering in the greater omentum is enhanced by a periosteal transplant in a miniature pig model. Regen Med, 2019, 14(2): 127-138.
44.	Epple C, Haumer A, Ismail T, et al. Prefabrication of a large pedicled bone graft by engineering the germ for de novo vascularization and osteoinduction. Biomaterials, 2019, 192: 118-127.
45.	Wu X, Wang Q, Kang N, et al. The effects of different vascular carrier patterns on the angiogenesis and osteogenesis of BMSC-TCP-based tissue-engineered bone in beagle dogs. J Tissue Eng Regen Med, 2017, 11(2): 542-552.
46.	Dębski T, Kurzyk A, Ostrowska B, et al. Scaffold vascularization method using an adipose-derived stem cell (ASC)-seeded scaffold prefabricated with a flow-through pedicle. Stem Cell Res Ther, 2020, 11(1): 34.
47.	Charbonnier B, Baradaran A, Sato D, et al. Material-induced venosome-supported bone tubes. Adv Sci (Weinh), 2019, 6(17): 1900844.
48.	Spalthoff S, Jehn P, Zimmerer R, et al. Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on bone formation and matrix degeneration. Int J Oral Maxillofac Surg, 2015, 44(6): 791-797.
49.	王思明, 阚娜, 张磊, 等. β-磷酸三钙预构中心血管化人工骨的实验研究. 南京医科大学学报 (自然科学版), 2017, 37(1): 58-61.
50.	Erol OO, Sira M. New capillary bed formation with a surgically constructed arteriovenous fistula. Plast Reconstr Surg, 1980, 66(1): 109-115.
51.	Ma D, Ren L, Cao Z, et al. Prefabrication of axially vascularized bone by combining β-tricalciumphosphate, arteriovenous loop, and cell sheet technique. Tissue Eng Regen Med, 2016, 13(5): 579-584.
52.	Eweida A, Fathi I, Eltawila AM, et al. Pattern of bone generation after irradiation in vascularized tissue engineered constructs. J Reconstr Microsurg, 2018, 34(2): 130-137.
53.	Eweida A, Frisch O, Giordano FA, et al. Axially vascularized tissue-engineered bone constructs retain their in vivo angiogenic and osteogenic capacity after high-dose irradiation. J Tissue Eng Regen Med, 2018, 12(2): e657-e668.
54.	Arkudas A, Lipp A, Buehrer G, et al. Pedicled transplantation of axially vascularized bone constructs in a critical size femoral defect. Tissue Eng Part A, 2018, 24(5-6): 479-492.
55.	Wong R, Donno R, Leon-Valdivieso CY, et al. Angiogenesis and tissue formation driven by an arteriovenous loop in the mouse. Sci Rep, 2019, 9(1): 10478.
56.	Schmidt VJ, Covi JM, Koepple C, et al. Flow induced microvascular network formation of therapeutic relevant arteriovenous (AV) loop-based constructs in response to ionizing radiation. Med Sci Monit, 2017, 23: 834-842.
57.	Yuan Q, Arkudas A, Horch RE, et al. Vascularization of the arteriovenous loop in a rat isolation chamber model-quantification of hypoxia and evaluation of its effects. Tissue Eng Part A, 2018, 24(9-10): 719-728.
58.	Zhou M, Hou J, Li Y, et al. The pro-angiogenic role of hypoxia inducible factor stabilizer FG-4592 and its application in an in vivo tissue engineering chamber model. Sci Rep, 2019, 9(1): 6035.
59.	Eweida AM, Nabawi AS, Abouarab M, et al. Enhancing mandibular bone regeneration and perfusion via axial vascularization of scaffolds. Clin Oral Investig, 2014, 18(6): 1671-1678.
60.	Eweida AM, Horch RE, Marei MK, et al. Axially vascularised mandibular constructs: Is it time for a clinical trial? J Craniomaxillofac Surg, 2015, 43(7): 1028-1032.
61.	Horch RE, Beier JP, Kneser U, et al. Successful human long-term application of in situ bone tissue engineering. J Cell Mol Med, 2014, 18(7): 1478-1485.
62.	Weigand A, Beier JP, Hess A, et al. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization. Tissue Eng Part A, 2015, 21(9-10): 1680-1694.
63.	Zhan W, Marre D, Mitchell GM, et al. Tissue engineering by intrinsic vascularization in an in vivo tissue engineering Chamber. J Vis Exp, 2016, 30(111): 54099.
64.	Watson E, Tatara AM, van den Beucken J, et al. An ovine model of in vivo bioreactor-based bone generation. Tissue Eng Part C Methods, 2020, 26(7): 384-396.
65.	Carlisle P, Marrs J, Gaviria L, et al. Quantifying vascular changes surrounding bone regeneration in a porcine mandibular defect using computed tomography. Tissue Eng Part C Methods, 2019, 25(12): 721-731.

1. Stevens MM, Marini RP, Schaefer D, et al. In vivo engineering of organs: the bone bioreactor. Proc Natl Acad Sci U S A, 2005, 102(32): 11450-11455.
2. Holt GE, Halpern JL, Dovan TT, et al. Evolution of an in vivo bioreactor. J Orthop Res, 2005, 23(4): 916-923.
3. Wang Z, Han L, Sun T, et al. Construction of tissue-engineered bone with differentiated osteoblasts from adipose-derived stem cell and coral scaffolds at an ectopic site. Br J Oral Maxillofac Surg, 2021, 59(1): 46-51.
4. Ma J, Yang F, Both SK, et al. Bone forming capacity of cell- and growth factor-based constructs at different ectopic implantation sites. J Biomed Mater Res A, 2015, 103(2): 439-450.
5. Sharma S, Sapkota D, Xue Y, et al. Delivery of VEGFA in bone marrow stromal cells seeded in copolymer scaffold enhances angiogenesis, but is inadequate for osteogenesis as compared with the dual delivery of VEGFA and BMP2 in a subcutaneous mouse model. Stem Cell Res Ther, 2018, 9(1): 23.
6. Wu H, Kang N, Wang Q, et al. The dose-effect relationship between the seeding quantity of human marrow mesenchymal stem cells and in vivo tissue-engineered bone yield. Cell transplantation, 2015, 24(10): 1957-1968.
7. Drouin G, Couture V, Lauzon MA, et al. Muscle injury-induced hypoxia alters the proliferation and differentiation potentials of muscle resident stromal cells. Skeletal muscle, 2019, 9(1): 18.
8. Molligan J, Mitchell R, Schon L, et al. Influence of bone and muscle injuries on the osteogenic potential of muscle progenitors: contribution of tissue environment to heterotopic ossification. Stem Cells Transl Med, 2016, 5(6): 745-753.
9. Zhou M, Peng X, Mao C, et al. The value of SPECT/CT in monitoring prefabricated tissue-engineered bone and orthotopic rhBMP-2 implants for mandibular reconstruction. PLoS One, 2015, 10(9): e0137167.
10. Khouri RK, Koudsi B, Reddi H. Tissue transformation into bone in vivo. A potential practical application. JAMA, 1991, 266(14): 1953-1955.
11. Mesimäki K, Lindroos B, Törnwall J, et al. Novel maxillary reconstruction with ectopic bone formation by GMP adipose stem cells. Int J Oral Maxillofac Surg, 2009, 38(3): 201-209.
12. Kokemueller H, Spalthoff S, Nolff M, et al. Prefabrication of vascularized bioartificial bone grafts in vivo for segmental mandibular reconstruction: experimental pilot study in sheep and first clinical application. Int J Oral Maxillofac Surg, 2010, 39(4): 379-387.
13. Zimmerer RM, Jehn P, Kokemüller H, et al. In vivo tissue engineered bone versus autologous bone: stability and structure. Int J Oral Maxillofac Surg, 2017, 46(3): 385-393.
14. Zhou M, Peng X, Mao C, et al. Primate mandibular reconstruction with prefabricated, vascularized tissue-engineered bone flaps and recombinant human bone morphogenetic protein-2 implanted in situ. Biomaterials, 2010, 31(18): 4935-4943.
15. Beck-Broichsitter BE, Becker ST, Seitz H, et al. Endocultivation: Histomorphological effects of repetitive rhBMP-2 application into prefabricated hydroxyapatite scaffolds at extraskeletal sites. J Craniomaxillofac Surg, 2015, 43(6): 981-988.
16. Beck-Broichsitter BE, Becker ST, Seitz H, et al. Endocultivation: continuous application of rhBMP-2 via mini-osmotic pumps to induce bone formation at extraskeletal sites. Int J Oral Maxillofac Surg, 2017, 46(5): 655-661.
17. 张迅, 周立, 侯建玺, 等. 局部缓释VEGF对兔同种异体骨异位预构骨皮瓣的影响. 中华显微外科杂志, 2016, 39(6): 574-577.
18. Ichikawa K, Ohta Y, Mamoto K, et al. Local co-application of zoledronate promotes long-term maintenance of newly formed bone induced by recombinant human bone morphogenetic protein 2. Biochem Biophys Res Commun, 2016, 480(3): 314-320.
19. Tsagarakis M, Spyropoulou GA, Lykoudis E, et al. The use of vascularized fascia as carrier in cases of prelaminated fasciocartilaginous and osseofascial flaps. J Reconstr Microsurg, 2016, 32(4): 301-308.
20. Aliyev A, Ekin Ö, Bitik O, et al. A novel method of neo-osseous flap prefabrication: induction of free calvarial periosteum with bioactive glass. J Reconstr Microsurg, 2018, 34(5): 307-314.
21. Leonhardt H, Pradel W, Mai R, et al. Prefabricated bony radial forearm flap for secondary mandible reconstruction after radiochemotherapy. Head Neck, 2009, 31(12): 1579-1587.
22. Sadigh PL, Jeng SF. Prelamination of the anterolateral thigh flap with a fibula graft to successfully reconstruct a mandibular defect. Plast Reconstr Surg Glob Open, 2015, 3(8): e497.
23. Dou H, Wang G, Xing N, et al. Repair of large segmental bone defects with fascial flap-wrapped allogeneic bone. J Orthop Surg Res, 2016, 11(1): 162.
24. Fan H, Zeng X, Wang X, et al. Efficacy of prevascularization for segmental bone defect repair using β-tricalcium phosphate scaffold in rhesus monkey. Biomaterials, 2014, 35(26): 7407-7415.
25. Roberts SJ, van Gastel N, Carmeliet G, et al. Uncovering the periosteum for skeletal regeneration: the stem cell that lies beneath. Bone, 2015, 70: 10-18.
26. Zhang H, Mao X, Zhao D, et al. Three dimensional printed polylactic acid-hydroxyapatite composite scaffolds for prefabricating vascularized tissue engineered bone: An in vivo bioreactor model. Sci Rep, 2017, 7(1): 15255.
27. Huang RL, Tremp M, Ho CK, et al. Prefabrication of a functional bone graft with a pedicled periosteal flap as an in vivo bioreactor. Sci Rep, 2017, 7(1): 18038.
28. Nau C, Henrich D, Seebach C, et al. Treatment of large bone defects with a vascularized periosteal flap in combination with biodegradable scaffold seeded with bone marrow-derived mononuclear cells: An experimental study in rats. Tissue Eng Part A, 2016, 22(1-2): 133-141.
29. Nau C, Henrich D, Seebach C, et al. Tissue engineered vascularized periosteal flap enriched with MSC/EPCs for the treatment of large bone defects in rats. Int J Mol Med, 2017, 39(4): 907-917.
30. Gallardo-Calero I, Barrera-Ochoa S, Manzanares MC, et al. Vascularized periosteal flaps accelerate osteointegration and revascularization of allografts in rats. Clin Orthop Relat Res, 2019, 477(4): 741-755.
31. Tatara AM, Kretlow JD, Spicer PP, et al. Autologously generated tissue-engineered bone flaps for reconstruction of large mandibular defects in an ovine model. Tissue Eng Part A, 2015, 21(9-10): 1520-1528.
32. Tatara AM, Shah SR, Demian N, et al. Reconstruction of large mandibular defects using autologous tissues generated from in vivo bioreactors. Acta Biomater, 2016, 45: 72-84.
33. Tatara AM, Koons GL, Watson E, et al. Biomaterials-aided mandibular reconstruction using in vivo bioreactors. Proc Natl Acad Sci U S A, 2019, 116(14): 6954-6963.
34. Watson E, Smith BT, Smoak MM, et al. Localized mandibular infection affects remote in vivo bioreactor bone generation. Biomaterials, 2020, 256: 120185.
35. Wei J, Herrler T, Dai C, et al. Guided self-generation of vascularized neo-bone for autologous reconstruction of large mandibular defects. J Craniofac Surg, 2016, 27(4): 958-962.
36. Zhao D, Jiang W, Wang Y, et al. Three-dimensional-printed poly-L-lactic acid scaffolds with different pore sizes influence periosteal distraction osteogenesis of a rabbit skull. Biomed Res Int, 2020, 2020: 7381391.
37. Naujokat H, Açil Y, Harder S, et al. Osseointegration of dental implants in ectopic engineered bone in three different scaffold materials. Int J Oral Maxillofac Surg, 2020, 49(1): 135-142.
38. Li J, Zhi W, Xu T, et al. Ectopic osteogenesis and angiogenesis regulated by porous architecture of hydroxyapatite scaffolds with similar interconnecting structure in vivo. Regen Biomater, 2016, 3(5): 285-297.
39. Wiltfang J, Rohnen M, Egberts JH, et al. Man as a living bioreactor: Prefabrication of a custom vascularized bone graft in the gastrocolic omentum. Tissue Eng Part C Methods, 2016, 22(8): 740-746.
40. Naujokat H, Açil Y, Gülses A, et al. Man as a living bioreactor: Long-term histological aspects of a mandibular replacement engineered in the patient’s own body. Int J Oral Maxillofac Surg, 2018, 47(11): 1481-1487.
41. Birkenfeld F, Sengebusch A, Völschow C, et al. Endocultivation of scaffolds with recombinant human bone morphogenetic protein-2 and VEGF₁₆₅ in the omentum majus in a rabbit model. Tissue Eng Part C Methods, 2017, 23(12): 842-849.
42. Birkenfeld F, Sengebusch A, Völschow C, et al. Scaffold implantation in the omentum majus of rabbits for new bone formation. J Craniomaxillofac Surg, 2019, 47(8): 1274-1279.
43. Naujokat H, Lipp M, Açil Y, et al. Bone tissue engineering in the greater omentum is enhanced by a periosteal transplant in a miniature pig model. Regen Med, 2019, 14(2): 127-138.
44. Epple C, Haumer A, Ismail T, et al. Prefabrication of a large pedicled bone graft by engineering the germ for de novo vascularization and osteoinduction. Biomaterials, 2019, 192: 118-127.
45. Wu X, Wang Q, Kang N, et al. The effects of different vascular carrier patterns on the angiogenesis and osteogenesis of BMSC-TCP-based tissue-engineered bone in beagle dogs. J Tissue Eng Regen Med, 2017, 11(2): 542-552.
46. Dębski T, Kurzyk A, Ostrowska B, et al. Scaffold vascularization method using an adipose-derived stem cell (ASC)-seeded scaffold prefabricated with a flow-through pedicle. Stem Cell Res Ther, 2020, 11(1): 34.
47. Charbonnier B, Baradaran A, Sato D, et al. Material-induced venosome-supported bone tubes. Adv Sci (Weinh), 2019, 6(17): 1900844.
48. Spalthoff S, Jehn P, Zimmerer R, et al. Heterotopic bone formation in the musculus latissimus dorsi of sheep using β-tricalcium phosphate scaffolds: evaluation of an extended prefabrication time on bone formation and matrix degeneration. Int J Oral Maxillofac Surg, 2015, 44(6): 791-797.
49. 王思明, 阚娜, 张磊, 等. β-磷酸三钙预构中心血管化人工骨的实验研究. 南京医科大学学报 (自然科学版), 2017, 37(1): 58-61.
50. Erol OO, Sira M. New capillary bed formation with a surgically constructed arteriovenous fistula. Plast Reconstr Surg, 1980, 66(1): 109-115.
51. Ma D, Ren L, Cao Z, et al. Prefabrication of axially vascularized bone by combining β-tricalciumphosphate, arteriovenous loop, and cell sheet technique. Tissue Eng Regen Med, 2016, 13(5): 579-584.
52. Eweida A, Fathi I, Eltawila AM, et al. Pattern of bone generation after irradiation in vascularized tissue engineered constructs. J Reconstr Microsurg, 2018, 34(2): 130-137.
53. Eweida A, Frisch O, Giordano FA, et al. Axially vascularized tissue-engineered bone constructs retain their in vivo angiogenic and osteogenic capacity after high-dose irradiation. J Tissue Eng Regen Med, 2018, 12(2): e657-e668.
54. Arkudas A, Lipp A, Buehrer G, et al. Pedicled transplantation of axially vascularized bone constructs in a critical size femoral defect. Tissue Eng Part A, 2018, 24(5-6): 479-492.
55. Wong R, Donno R, Leon-Valdivieso CY, et al. Angiogenesis and tissue formation driven by an arteriovenous loop in the mouse. Sci Rep, 2019, 9(1): 10478.
56. Schmidt VJ, Covi JM, Koepple C, et al. Flow induced microvascular network formation of therapeutic relevant arteriovenous (AV) loop-based constructs in response to ionizing radiation. Med Sci Monit, 2017, 23: 834-842.
57. Yuan Q, Arkudas A, Horch RE, et al. Vascularization of the arteriovenous loop in a rat isolation chamber model-quantification of hypoxia and evaluation of its effects. Tissue Eng Part A, 2018, 24(9-10): 719-728.
58. Zhou M, Hou J, Li Y, et al. The pro-angiogenic role of hypoxia inducible factor stabilizer FG-4592 and its application in an in vivo tissue engineering chamber model. Sci Rep, 2019, 9(1): 6035.
59. Eweida AM, Nabawi AS, Abouarab M, et al. Enhancing mandibular bone regeneration and perfusion via axial vascularization of scaffolds. Clin Oral Investig, 2014, 18(6): 1671-1678.
60. Eweida AM, Horch RE, Marei MK, et al. Axially vascularised mandibular constructs: Is it time for a clinical trial? J Craniomaxillofac Surg, 2015, 43(7): 1028-1032.
61. Horch RE, Beier JP, Kneser U, et al. Successful human long-term application of in situ bone tissue engineering. J Cell Mol Med, 2014, 18(7): 1478-1485.
62. Weigand A, Beier JP, Hess A, et al. Acceleration of vascularized bone tissue-engineered constructs in a large animal model combining intrinsic and extrinsic vascularization. Tissue Eng Part A, 2015, 21(9-10): 1680-1694.
63. Zhan W, Marre D, Mitchell GM, et al. Tissue engineering by intrinsic vascularization in an in vivo tissue engineering Chamber. J Vis Exp, 2016, 30(111): 54099.
64. Watson E, Tatara AM, van den Beucken J, et al. An ovine model of in vivo bioreactor-based bone generation. Tissue Eng Part C Methods, 2020, 26(7): 384-396.
65. Carlisle P, Marrs J, Gaviria L, et al. Quantifying vascular changes surrounding bone regeneration in a porcine mandibular defect using computed tomography. Tissue Eng Part C Methods, 2019, 25(12): 721-731.

Chinese Journal of Reparative and Reconstructive Surgery

Research progress of in vivo bioreactor for bone tissue engineering

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