Construction and evaluation of a novel tissue‑engineered bone device

Chang,Zhengqi; Xing,Junchao; Yu,Xiuchun

doi:10.3892/etm.2021.10600

Construction and evaluation of a novel tissue‑engineered bone device

Authors:
- Zhengqi Chang
- Junchao Xing
- Xiuchun Yu
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Affiliations: Department of Orthopedics, 960th Hospital of PLA, Jinan, Shandong 250031, P.R. China, Department of Orthopedics, Southwest Hospital, Third Military Medical University, Chongqing 400038, P.R. China
Published online on: August 12, 2021 https://doi.org/10.3892/etm.2021.10600
Article Number: 1166
Copyright: © Chang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Tissue‑engineered bones (TEB) are a promising strategy for treating large segmental bone defects. However, the application of TEB is greatly limited by technical and logistical issues caused by the viable cells used. The aim of the present study was to devise novel TEB, termed functional TEB (fTEB) using devitalized mesenchymal stem cells (MSCs) with the functional proteins retained. TEB were fabricated by seeding MSCs on demineralized bone matrix (DBM) scaffolds. fTEB were prepared with deep hyperthermia treatment. Total proteins were extracted from fTEB and conditioned media (CM) were prepared. The effects of fTEB‑CM on the proliferation, differentiation and migration of host MSCs were assessed. Following lyophilization, the majority of the MSCs were devitalized, but the proteins within the TEB were retained in fTEB. Similar to TEB, fTEB outperformed the DBM in inducing migration, proliferation and osteogenic differentiation in MSCs. The abundance of cytokines in fTEB was also determined. fTEB were shown to be a promising alternative to TEB. Thus, they might serve as off‑the‑shelf tissue engineering products, meeting the high demands for bone substitutes in the clinical setting.

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1	Quarto R, Mastrogiacomo M, Cancedda R, Kutepov SM, Mukhachev V, Lavroukov A, Kon E and Marcacci M: Repair of large bone defects with the use of autologous bone marrow stromal cells. New Engl J Med. 344:385–386. 2001.PubMed/NCBI View Article : Google Scholar
2	Xu JZ, Qin H, Wang XQ, Zhou Q, Luo F, Hou TY and He QY: Repair of large segmental bone defects using bone marrow stromal cells with demineralized bone matrix. Orthop Surg. 1:34–41. 2009.PubMed/NCBI View Article : Google Scholar
3	Kitoh H, Kitakoji T, Tsuchiya H, Katoh M and Ishiguro N: Distraction osteogenesis of the lower extremity in patients with achondroplasia/hypochondroplasia treated with transplantation of culture-expanded bone marrow cells and platelet-rich plasma. J Pediatr Orthop. 27:629–634. 2007.PubMed/NCBI View Article : Google Scholar
4	Xing J, Lu Y, Cui Y, Zhu X, Luo F, Xie Z, Wu X, Deng M, Xu J and Hou T: A standardized and quality-controllable protocol of constructing individual tissue-engineered grafts applicable to treating large bone defects. Tissue Eng Part C Methods. 25:137–147. 2019.PubMed/NCBI View Article : Google Scholar
5	Tasso R, Augello A, Boccardo S, Salvi S, Carida M, Postiglione F, Fais F, Truini M, Cancedda R and Pennesi G: Recruitment of a host's osteoprogenitor cells using exogenous mesenchymal stem cells seeded on porous ceramic. Tissue Eng Part A. 15:2203–2212. 2009.PubMed/NCBI View Article : Google Scholar
6	Tortelli F, Tasso R, Loiacono F and Cancedda R: The development of tissue-engineered bone of different origin through endochondral and intramembranous ossification following the implantation of mesenchymal stem cells and osteoblasts in a murine model. Biomaterials. 31:242–249. 2010.PubMed/NCBI View Article : Google Scholar
7	Becquart P, Cambon-Binder A, Monfoulet LE, Bourguignon M, Vandamme K, Bensidhoum M, Petite H and Logeart-Avramoglou D: Ischemia is the prime but not the only cause of human multipotent stromal cell death in tissue-engineered constructs in vivo. Tissue Eng Part A. 18:2084–2094. 2012.PubMed/NCBI View Article : Google Scholar
8	Amini AR, Laurencin CT and Nukavarapu SP: Bone tissue engineering: Recent advances and challenges. Crit Rev Biomed Eng. 40:363–408. 2012.PubMed/NCBI View Article : Google Scholar
9	Xing J, Hou T, Jin H, Luo F, Change Z, Li Z, Xie Z and Xu J: Inflammatory microenvironment changes the secretory profile of mesenchymal stem cells to recruit mesenchymal stem cells. Cell Physiol Biochem. 33:905–919. 2014.PubMed/NCBI View Article : Google Scholar
10	Habib HS, Halawa TF and Atta HM: Therapeutic applications of mesenchymal stroma cells in pediatric diseases: Current aspects and future perspectives. Med Sci Monit. 17:RA233–RA239. 2011.PubMed/NCBI View Article : Google Scholar
11	Hou T, Xu J, Wu X, Xie Z, Luo F, Zhang Z and Zeng L: Umbilical cord Wharton's Jelly: A new potential cell source of mesenchymal stromal cells for bone tissue engineering. Tissue Eng Part A. 15:2325–2334. 2009.PubMed/NCBI View Article : Google Scholar
12	Horwitz EM, Prockop DJ, Fitzpatrick LA, Koo WW, Gordon PL, Neel M, Sussman M, Orchard P, Marx JC, Pyeritz RE and Brenner MK: Transplantability and therapeutic effects of bone marrow-derived mesenchymal cells in children with osteogenesis imperfecta. Nat Med. 5:309–313. 1999.PubMed/NCBI View Article : Google Scholar
13	Horwitz EM, Gordon PL, Koo WK, Marx JC, Neel MD, McNall RY, Muul L and Hofmann T: Isolated allogeneic bone marrow-derived mesenchymal cells engraft and stimulate growth in children with osteogenesis imperfecta: Implications for cell therapy of bone. Proc Natl Acad Sci USA. 99:8932–8937. 2002.PubMed/NCBI View Article : Google Scholar
14	Gnecchi M, Zhang Z, Ni A and Dzau VJ: Paracrine mechanisms in adult stem cell signaling and therapy. Circ Res. 103:1204–1219. 2008.PubMed/NCBI View Article : Google Scholar
15	Li W, Liu Y, Zhang P, Tang Y, Zhou M, Jiang W, Zhang X, Wu G and Zhou Y: Tissue-engineered bone immobilized with human adipose stem cells-derived exosomes promotes bone regeneration. ACS Appl Mater Interfaces. 10:5240–5254. 2019.PubMed/NCBI View Article : Google Scholar
16	Chen FM, Wu LA, Zhang M, Zhang R and Sun HH: Homing of endogenous stem/progenitor cells for in situ tissue regeneration: Promises, strategies, and translational perspectives. Biomaterials. 32:3189–3209. 2011.PubMed/NCBI View Article : Google Scholar
17	Chen HW, Chen HY, Wang LT, Wang FH, Fang LW, Lai HY, Chen HH, Lu J, Hung MS, Cheng Y, et al: Mesenchymal stem cells tune the development of monocyte-derived dendritic cells toward a myeloid-derived suppressive phenotype through growth-regulated oncogene chemokines. J Immunol. 190:5065–5077. 2013.PubMed/NCBI View Article : Google Scholar
18	Ringe J, Strassburg S, Neumann K, Endres M, Notter M, Burmester GR, Kaps C and Sittinger M: Towards in situ tissue repair: Human mesenchymal stem cells express chemokine receptors CXCR1, CXCR2 and CCR2, and migrate upon stimulation with CXCL8 but not CCL2. J Cell Biochem. 101:135–146. 2007.PubMed/NCBI View Article : Google Scholar
19	Keeley EC, Mehrad B and Strieter RM: CXC chemokines in cancer angiogenesis and metastases. Adv Cancer Res. 106:91–111. 2010.PubMed/NCBI View Article : Google Scholar
20	Joukhadar J, Nevers T and Kalkunte S: New frontiers in reproductive immunology research: Bringing bedside problems to the bench. Exp Rev Clin Immunol. 7:575–577. 2011.PubMed/NCBI View Article : Google Scholar
21	Li F, Whyte N and Niyibizi C: Differentiating multipotent mesenchymal stromal cells generate factors that exert paracrine activities on exogenous MSCs: Implications for paracrine activities in bone regeneration. Biochem Biophys Res Commun. 426:475–479. 2012.PubMed/NCBI View Article : Google Scholar
22	Ramasamy R, Tong CK, Yip WK, Vellasamy S, Tan BC and Seow HF: Basic fibroblast growth factor modulates cell cycle of human umbilical cord-derived mesenchymal stem cells. Cell Prolif. 45:132–139. 2012.PubMed/NCBI View Article : Google Scholar
23	Rose LC, Fitzsimmons R, Lee P, Krawetz R, Rancourt DE and Uludag H: Effect of basic fibroblast growth factor in mouse embryonic stem cell culture and osteogenic differentiation. J Tissue Eng Regen Med. 7:371–382. 2013.PubMed/NCBI View Article : Google Scholar
24	Dighe PA, Viswanathan P, Mruthunjaya AK and Seetharam RN: Effect of bFGF on HLA-DR expression of human bone marrow-derived mesenchymal stem cells. J Stem Cells. 8:43–57. 2013.PubMed/NCBI
25	Kim TH, Kim JJ and Kim HW: Basic fibroblast growth factor-loaded, mineralized biopolymer-nanofiber scaffold improves adhesion and proliferation of rat mesenchymal stem cells. Biotechnol Lett. 36:383–390. 2014.PubMed/NCBI View Article : Google Scholar
26	Chen L, Jiang W, Huang J, He BC, Zuo GW, Zhang W, Luo Q, Shi Q, Zhang BQ, Wagner ER, et al: Insulin-like growth factor 2 (IGF-2) potentiates BMP-9-induced osteogenic differentiation and bone formation. J Bone Miner Res. 25:2447–2459. 2010.PubMed/NCBI View Article : Google Scholar
27	Fukuyo S, Yamaoka K, Sonomoto K, Oshita K, Okada Y, Saito K, Yoshida Y, Kanazawa T, Minami Y and Tanaka Y: IL-6-accelerated calcification by induction of ROR2 in human adipose tissue-derived mesenchymal stem cells is STAT3 dependent. Rheumatology (Oxford). 53:1282–1290. 2014.PubMed/NCBI View Article : Google Scholar
28	Berendsen AD and Olsen BR: How vascular endothelial growth factor-A (VEGF) regulates differentiation of mesenchymal stem cells. J Histochem Cytochem. 62:103–108. 2014.PubMed/NCBI View Article : Google Scholar
29	Bai Y, Li P, Yin G, Huang Z, Liao X, Chen X and Yao Y: BMP-2, VEGF and bFGF synergistically promote the osteogenic differentiation of rat bone marrow-derived mesenchymal stem cells. Biotechnol Lett. 35:301–308. 2013.PubMed/NCBI View Article : Google Scholar
30	Yuan S, Pan Q, Fu CJ and Bi Z: Effect of growth factors (BMP-4/7 & bFGF) on proliferation & osteogenic differentiation of bone marrow stromal cells. Indian J Med Res. 138:104–110. 2013.PubMed/NCBI
31	Hu F, Wang X, Liang G, Lv L, Zhu Y, Sun B and Xiao Z: Effects of epidermal growth factor and basic fibroblast growth factor on the proliferation and osteogenic and neural differentiation of adipose-derived stem cells. Cell Reprogram. 15:224–232. 2013.PubMed/NCBI View Article : Google Scholar