This study aimed to develop bone regenerative therapeutic strategies, based on the addition of bone marrow stromal cells (BMSC) on bioglass/collagen (BG/COL) scaffolds. For this purpose, an in vivo study was conducted using tissue response of the BG/COL scaffolds combined with BMSC in a critical-size defects. Wistar rats were submitted to the surgical procedure to perform the cranial critical size bone defects and distributed in four groups (20 animals per group): Control Group (CG) (rats submitted to the cranial bone defect surgery without treatment), Bioglass Group (BG) (rats treated with BG), BG/COL Group (rats treated with BG/COL) and Bioglass/Collagen and BMSC Group (BG/COL/BMSC) (rats treated with BG/COL scaffolds enriched with BMSCs). Animals were euthanized 15 and 30 days after surgery. Scanning electron microscopy, histopathological and immunohistochemistry analysis were used. SEM analysis demonstrated that porous scaffolds were obtained, and Col fibers were successfully impregnated to BG matrices. The implantation of the BMSC on BG/COL based scaffolds was effective in stimulating newly bone formation and produced an increased immunoexpression of markers related to the bone repair. These results highlight the potential of BG/COL scaffolds and BMSCs to be used as a therapeutic approach for bone regeneration.
BisignanoCJamesSLAbadyGGet al; GBD 2019 Fracture Collaborators. Global, regional, and national burden of bone fractures in 204 countries and territories, 1990–2019: a systematic analysis from the global burden of disease study 2019. Lancet Healthy Longev2021; 2(9): e580–e592.
2.
CauleyJA. The global burden of fractures. Lancet Healthy Longev2021; 2(9): e535–e536.
3.
MeinbergEGClarkDMiclauKR, et al.Fracture repair in the elderly: clinical and experimental considerations. Injury2019; 50(Suppl 1): S62–S65.
4.
ChengCShobackD. Mechanisms underlying normal fracture healing and risk factors for delayed Healing. Curr Osteoporos Rep2019; 17(1): 36–47.
5.
SchlickeweiCWKleinertzHThiesenDM, et al.Current and future concepts for the treatment of impaired fracture healing. Int J Mol Sci2019; 20(22): 5805.
6.
KangariPTalaei-KhozaniTRazeghian-JahromiI, et al.Mesenchymal stem cells: amazing remedies for bone and cartilage defects. Stem Cell Res Ther2020; 11(1): 492.
7.
AmaroliAColomboEZekiyA, et al.Interaction between laser light and osteoblasts: photobiomodulation as a trend in the management of socket bone preservation—a review. Biology (Basel)2020; 9(11): 409.
8.
CaoDDingJ. Recent advances in regenerative biomaterials. Regen Biomater2022; 9: rbac098.
9.
GavinhoSRPáduaASSá-NogueiraI, et al.Biocompatibility, bioactivity, and antibacterial behaviour of cerium-containing bioglass®. Nanomaterials2022; 12(24): 4479.
10.
KomoriT.. Roles of Runx2 in skeletal development. Adv Exp Med Biol2017; 962: 83–93.
11.
ToosiSNaderi-MeshkinHEsmailzadehZ, et al.Bioactive glass-collagen/poly (glycolic acid) scaffold nanoparticles exhibit improved biological properties and enhance osteogenic lineage differentiation of mesenchymal stem cells. Front Bioeng Biotechnol2022; 10: 963996.
12.
ParisiJRFernandesKRAvanziIR, et al.Incorporation of collagen from marine sponges (spongin) into hydroxyapatite samples: characterization and in vitro biological evaluation. Mar Biotechnol2019; 21(1): 30–37. DOI: 10.1007/s10126-018-9855-z.
13.
FernandesKRMagriAMPKidoHW, et al.Characterization and biological evaluation of the introduction of PLGA into biosilicate®. J Biomed Mater Res B Appl Biomater2017; 105(5): 1063–1074. DOI: 10.1002/jbm.b.33654.
14.
WuJYaoMZhangY, et al.Biomimetic three-layered membranes comprising (poly)-ε-caprolactone, collagen and mineralized collagen for guided bone regeneration. Regen Biomater2021; 8(6): rbab065.
15.
Zurita-MéndezNNCarbajal-De la TorreGFlores-MerinoM V., et al.Development of bioactive glass-collagen-hyaluronic acid-polycaprolactone scaffolds for tissue engineering applications. Front Bioeng Biotechnol2022; 10: 825903.
16.
SultanSThomasNVargheseM, et al.The design of 3D-printed polylactic acid–bioglass composite scaffold: a potential implant material for bone tissue engineering. Molecules2022; 27(21): 7214.
17.
NijsureMPPastakiaMSpanoJ, et al.Bioglass incorporation improves mechanical properties and enhances cell-mediated mineralization on electrochemically aligned collagen threads. J Biomed Mater Res A2017; 105(9): 2429–2440. DOI: 10.1002/jbm.a.36102.
18.
SharifiEAzamiMKajbafzadehA-M, et al.Preparation of a biomimetic composite scaffold from gelatin/collagen and bioactive glass fibers for bone tissue engineering. Mater Sci Eng C [Internet]2016; 59: 533–541. Available from: https://linkinghub.elsevier.com/retrieve/pii/S0928493115303635
19.
RoweMJKamockiKPankajakshanD, et al.Dimensionally stable and bioactive membrane for guided bone regeneration: an in vitro study. J Biomed Mater Res B Appl Biomater2016; 104(3): 594–605. DOI: 10.1002/jbm.b.33430.
20.
CalabreseGGiuffridaRForteS, et al.Human adipose-derived mesenchymal stem cells seeded into a collagen-hydroxyapatite scaffold promote bone augmentation after implantation in the mouse. Sci Rep2017; 7(1): 7110.
WangCLaiJLiK, et al.Cryogenic 3D printing of dual-delivery scaffolds for improved bone regeneration with enhanced vascularization. Bioact Mater2021; 6(1): 137–145.
23.
ArthurAGronthosS. Clinical application of bone marrow mesenchymal stem/stromal cells to repair skeletal tissue. Int J Mol Sci2020; 21(24): 9759.
24.
JinY-ZLeeJH. Mesenchymal stem cell therapy for bone regeneration. Clin Orthop Surg2018; 10(3): 271–278.
25.
Abdel MeguidEKeYJiJ, et al.Stem cells applications in bone and tooth repair and regeneration: new insights, tools, and hopes. J Cell Physiol2018; 233(3): 1825–1835.
26.
Hernandez-HurtadoAABorrego-SotoGMarino-MartinezIA, et al.Implant composed of demineralized bone and mesenchymal stem cells genetically modified with AdBMP2/AdBMP7 for the regeneration of bone fractures in ovis aries. Stem Cells Int [Internet]2016; 2016: 1–12. Available from: https://www.hindawi.com/journals/sci/2016/7403890/
27.
HussainSTamizhselviRGeorgeL, et al. Assessment of the role of noni (Morinda citrifolia) juice for inducing osteoblast differentiation in isolated rat bone marrow derived mesenchymal stem cells. Int J Stem Cells [Internet]2016; 9(2): 221–229. DOI: 10.15283/ijsc16024.
28.
GurumurthyBPalPGriggsJA, et al.Optimization of collagen-elastin-like polypeptide-bioglass scaffold composition for osteogenic differentiation of adipose-derived stem cells. Materialia2020; 9: 100572.
29.
KidoHWGabbai-ArmelinPRAvanziIR, et al.Vacuumed collagen-impregnated bioglass scaffolds: characterization and influence on proliferation and differentiation of bone marrow stromal cells. J Biomed Mater Res2018; 107: 211–222.
30.
KidoHWTimCRBossiniPS, et al.Porous bioactive scaffolds: characterization and biological performance in a model of tibial bone defect in rats. J Mater Sci Mater Med2015; 26(2): 74. DOI:10.1007/s10856-015-5411-9.
31.
CamiloCCSilveiraCAEFaedaRS, et al.Bone response to porous alumina implants coated with bioactive materials, observed using different characterization techniques. J Appl Biomater Funct Mater2017; 15(3): e223–e235. DOI: 10.5301/jabfm.5000347.
32.
ZhangLChanC. Isolation and enrichment of rat mesenchymal stem cells (MSCs) and separation of single-colony derived MSCs. J Vis Exp [Internet]2010; (37). Available from: http://www.jove.com/index/Details.stp?ID=1852
KubotaTHasuikeAOzawaY, et al.Regenerative capacity of augmented bone in rat calvarial guided bone augmentation model. J Periodontal Implant Sci2017; 47(2): 77–85. DOI: 10.5051/jpis.2017.47.2.77.
35.
XieCReynoldsDAwadH, et al.Structural bone allograft combined with genetically engineered mesenchymal stem cells as a novel platform for bone tissue engineering. Tissue Eng2007; 13(3): 435–445. DOI: 10.1089/ten.2006.0182.
36.
GranitoRNRennõACRavagnaniC, et al.In vivo biological performance of a novel highly bioactive glass-ceramic (biosilicate®): a biomechanical and histomorphometric study in rat tibial defects. J Biomed Mater Res2011; 97B: 139–147.
37.
MagriAMPFernandesKRUenoFR, et al.Osteoconductive properties of two different bioactive glass forms (powder and fiber) combined with collagen. Appl Surf Sci2017; 423: 557–565. Available from: https://linkinghub.elsevier.com/retrieve/pii/S016943321731807X
38.
MagriAMPFernandesKRAssisL, et al.Photobiomodulation and bone healing in diabetic rats: evaluation of bone response using a tibial defect experimental model. Lasers Med Sci2015; 30(7): 1949–1957. DOI: 10.1007/s10103-015-1789-3.
39.
TimCRPintoKNZRossiBRO, et al.Low-level laser therapy enhances the expression of osteogenic factors during bone repair in rats. Lasers Med Sci2014; 29(1): 147–156. DOI: 10.1007/s10103-013-1302-9.
40.
CaddeoSMattioli-BelmonteMCassinoC, et al.Newly-designed collagen/polyurethane bioartificial blend as coating on bioactive glass-ceramics for bone tissue engineering applications. Mater Sci Eng C Mater Biol Appl2019; 96: 218–233.
41.
DhinasekaranDVimalrajSRajendranAR, et al.Bio-inspired multifunctional collagen/electrospun bioactive glass membranes for bone tissue engineering applications. Mater Sci Eng C Mater Biol Appl2021; 126: 111856.
42.
PittengerMFDischerDEPéaultBM, et al.Mesenchymal stem cell perspective: cell biology to clinical progress. Npj Regen Med2019; 4(1): 22.
43.
LeePSHeinemannCZhengK, et al.The interplay of collagen/bioactive glass nanoparticle coatings and electrical stimulation regimes distinctly enhanced osteogenic differentiation of human mesenchymal stem cells. Acta Biomater2022; 149: 373–386.
44.
KroschwaldLMAllerdtFBernhardtA, et al.Artificial extracellular matrices containing bioactive glass nanoparticles promote osteogenic differentiation in human mesenchymal stem cells. Int J Mol Sci2021; 22(23): 12819.
45.
Alvarez EchazúMRenouSAlvarezG, et al.A collagen‐silica‐ based biocomposite for potential application in bone tissue engineering. J Biomed Mater Res A2022; 110(2): 331–340.
46.
FievetLSerratriceNBrulinB, et al.A comparative in vitro and in vivo study of osteogenicity by using two biomaterials and two human mesenchymal stem cell subtypes. Front Cell Dev Biol2022; 10: 913539.
47.
KirankumarSGurusamyNRajasinghS, et al.Modern approaches on stem cells and scaffolding technology for osteogenic differentiation and regeneration. Exp Biol Med2022; 247(5): 433–445.
48.
DiomedeFD’AuroraMGugliandoloA, et al.Biofunctionalized scaffold in bone tissue repair. Int J Mol Sci2018; 19(4): 1022. Available from: https://www.ncbi.nlm.nih.gov/pubmed/29596323
49.
ZhaoLJiangSHantashBM. Transforming growth factor beta1 induces osteogenic differentiation of murine bone marrow stromal cells. Tissue Eng Part A [Internet]2010; 16(2): 725–733. DOI: 10.1089/ten.tea.2009.0495.
50.
ShakirSMacIsaacZMNaranS, et al.Transforming growth factor beta 1 augments calvarial defect healing and promotes suture regeneration. Tissue Eng Part A [Internet]2015; 21(5-6): 939–947. DOI: 10.1089/ten.tea.2014.0189.
51.
ChenJTuCTangX, et al.The combinatory effect of sinusoidal electromagnetic field and VEGF promotes osteogenesis and angiogenesis of mesenchymal stem cell-laden PCL/HA implants in a rat subcritical cranial defect. Stem Cell Res Ther2019; 10(1): 379.
52.
JinQYuanKLinW, et al.Comparative characterization of mesenchymal stem cells from human dental pulp and adipose tissue for bone regeneration potential. Artif Cells Nanomed Biotechnol2019; 47(1): 1577–1584.
53.
ShikimakaOBivolMSavaBA, et al.Hydroxyapatite–bioglass nanocomposites: structural, mechanical, and biological aspects. Beilstein J Nanotechnol2022; 13: 1490–1504.
54.
GhosalKChakrabortyDRoychowdhuryV, et al.Recent advancement of functional hydrogels toward diabetic wound management. ACS Omega2022; 7(48): 43364–43380.
