Treatment of large bone defects in load-bearing bone: traditional and novel bone grafts

Dan YU; Wenyi SHEN; Jiahui DAI; Huiyong ZHU

doi:10.1631/jzus.B2300669

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Review | Updated：2025-05-28

Treatment of large bone defects in load-bearing bone: traditional and novel bone grafts
Treatment of large bone defects in load-bearing bone: traditional and novel bone grafts
承重骨大段骨缺损的治疗：传统与新型骨移植材料
Journal of Zhejiang University-SCIENCE B (Biomedicine & Biotechnology) Vol. 26, Issue 5, Pages: 421-447(2025)
Affiliations：

1.Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310003, China
2.Department of Stomatology, Zhejiang University School of Medicine, Hangzhou 310058, China
Funds：
DOI：10.1631/jzus.B2300669
CLC：
CSTR：
Received：19 September 2023，

Revised：10 January 2024，

Published Online：30 April 2025，

Published：28 May 2025
Accepted：

余丹,沈文怡,戴家慧等.承重骨大段骨缺损的治疗：传统与新型骨移植材料[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(05):421-447.

Dan YU, Wenyi SHEN, Jiahui DAI, et al. Treatment of large bone defects in load-bearing bone: traditional and novel bone grafts[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(5): 421-447.
余丹,沈文怡,戴家慧等.承重骨大段骨缺损的治疗：传统与新型骨移植材料[J].浙江大学学报（英文版）（B辑：生物医学和生物技术）,2025,26(05):421-447. DOI： 10.1631/jzus.B2300669.

Dan YU, Wenyi SHEN, Jiahui DAI, et al. Treatment of large bone defects in load-bearing bone: traditional and novel bone grafts[J]. Journal of zhejiang university-science b (biomedicine & biotechnology), 2025, 26(5): 421-447. DOI： 10.1631/jzus.B2300669.

摘要

因严重创伤、肿瘤、囊肿以及广泛感染等原因造成的承重骨缺损是临床上常见的疾病。尽管骨具有自我修复和再生的潜能，但超过临界尺寸的大段骨缺损的修复仍是极大的临床挑战。传统的修复方法是使用自体骨或同种异体骨移植替代缺损部位缺失的骨组织，其中自体骨移植至今仍然是临床治疗的“金标准”。然而，传统骨移植材料的应用受到可获取骨量、供区并发症和免疫排斥等缺点的限制。近年来，临床对骨移植替代物的需求推动了新型骨移植材料的发展。除关注骨传导性和骨诱导性外，力学性能的优化是近年来增强新型骨移植材料治疗承重骨缺损可行性的重点。但大多数生物材料支架尚不能提供足够的力学强度。目前研究面临的核心挑战在于如何在机械需求和组织再生需求间找到适当的平衡。本文就传统和新型骨移植材料在承重骨缺损中的应用及其优缺点进行综述，并重点介绍了基于材料、结构和功能仿生的新型骨移植物发展策略，以期为未来的研究提供新的思路和方向。

Abstract

Large bone defects in load-bearing bone can result from tumor resection

osteomyelitis

trauma

and other factors. Although bone has the intrinsic potential to self-repair and regenerate

the repair of large bone defects which exceed a certain critical size remains a substantial clinical challenge. Traditionally

repair methods involve using autologous or allogeneic bone tissue to replace the lost bone tissue at defect sites

and autogenous bone grafting remains the “gold standard” treatment. However

the application of traditional bone grafts is limited by drawbacks such as the quantity of extractable bone

donor-site morbidities

and the risk of rejection. In recent years

the clinical demand for alternatives to traditional bone grafts has promoted the development of novel bone-grafting substitutes. In addition to osteoconductivity and osteoinductivity

optimal mechanical properties have recently been the focus of efforts to improve the treatment success of novel bone-grafting alternatives in load-bearing bone defects

but most biomaterial synthetic scaffolds cannot provide sufficient mechanical strength. A fundamental challenge is to find an appropriate balance between mechanical and tissue-regeneration requirements. In this review

the use of traditional bone grafts in load-bearing bone defects

as well as their advantages and disadvantages

is summarized and reviewed. Furthermore

we highlight recent development strategies for novel bone grafts appropriate for load-bearing bone defects based on substance

structural

and functional bionics to provide ideas and directions for future research.

关键词

Keywords

references

Adachi T , Osako Y , Tanaka M , et al. , 2006 . Framework for optimal design of porous scaffold microstructure by computational simulation of bone regeneration . Biomaterials , 27 ( 21 ): 3964 - 3972 . https://doi.org/10.1016/j.biomaterials.2006.02.039 https://doi.org/10.1016/j.biomaterials.2006.02.039

Almasi D , Iqbal N , Sadeghi M , et al. , 2016 . Preparation methods for improving PEEK’s bioactivity for orthopedic and dental application: a review . Int J Biomater , 2016 : 8202653 . https://doi.org/10.1155/2016/8202653 https://doi.org/10.1155/2016/8202653

An SH , Matsumoto T , Miyajima H , et al. , 2012 . Porous zirconia/hydroxyapatite scaffolds for bone reconstruction . Dent Mater , 28 ( 12 ): 1221 - 1231 . https://doi.org/10.1016/j.dental.2012.09.001 https://doi.org/10.1016/j.dental.2012.09.001

Ansari MAA , Golebiowska AA , Dash M , et al. , 2022 . Engineering biomaterials to 3D-print scaffolds for bone regeneration: practical and theoretical consideration . Biomater Sci , 10 ( 11 ): 2789 - 2816 . https://doi.org/10.1039/d2bm00035k https://doi.org/10.1039/d2bm00035k

Antebi B , Cheng XG , Harris JN , et al. , 2013 . Biomimetic collagen-hydroxyapatite composite fabricated via a novel perfusion-flow mineralization technique . Tissue Eng Part C Methods , 19 ( 7 ): 487 - 496 . https://doi.org/10.1089/ten.TEC.2012.0452 https://doi.org/10.1089/ten.TEC.2012.0452

Attias N , Lindsey RW , 2006 . CASE REPORTS: management of large segmental tibial defects using a cylindrical mesh cage . Clin Orthop Relat Res , 450 : 259 - 266 . https://doi.org/10.1097/01.blo.0000223982.29208.a4 https://doi.org/10.1097/01.blo.0000223982.29208.a4

Ayvaz M , Bekmez S , Yucekul A , et al. , 2018 . Titanium mesh cage as an alternative reconstruction method for epiphyseal-sparing tumour resections in children . J Pediatr Orthop B , 27 ( 4 ): 350 - 355 . https://doi.org/10.1097/BPB.0000000000000482 https://doi.org/10.1097/BPB.0000000000000482

Azadani MN , Zahedi A , Bowoto OK , et al. , 2022 . A review of current challenges and prospects of magnesium and its alloy for bone implant applications . Prog Biomater , 11 ( 1 ): 1 - 26 . https://doi.org/10.1007/s40204-022-00182-x https://doi.org/10.1007/s40204-022-00182-x

Bach AD , Kopp J , Stark GB , et al. , 2004 . The versatility of the free osteocutaneous fibula flap in the reconstruction of extremities after sarcoma resection . World J Surg Oncol , 2 : 22 . https://doi.org/10.1186/1477-7819-2-22 https://doi.org/10.1186/1477-7819-2-22

Bai F , Wang Z , Lu JX , et al. , 2010 . The correlation between the internal structure and vascularization of controllable porous bioceramic materials in vivo : a quantitative study . Tissue Eng Part A , 16 ( 12 ): 3791 - 3803 . https://doi.org/10.1089/ten.TEA.2010.0148 https://doi.org/10.1089/ten.TEA.2010.0148

Bashkuev M , Checa S , Postigo S , et al. , 2015 . Computational analyses of different intervertebral cages for lumbar spinal fusion . J Biomech , 48 ( 12 ): 3274 - 3282 . https://doi.org/10.1016/j.jbiomech.2015.06.024 https://doi.org/10.1016/j.jbiomech.2015.06.024

Bauer TW , Muschler GF , 2000 . Bone graft materials: an overview of the basic science . Clin Orthop Relat Res , 371 : 10 - 27 .

Bendtsen ST , Quinnell SP , Wei M , 2017 . Development of a novel alginate-polyvinyl alcohol-hydroxyapatite hydrogel for 3D bioprinting bone tissue engineered scaffolds . J Biomed Mater Res Part A , 105 ( 5 ): 1457 - 1468 . https://doi.org/10.1002/jbm.a.36036 https://doi.org/10.1002/jbm.a.36036

Beris AE , Lykissas MG , Korompilias AV , et al. , 2011 . Vascularized fibula transfer for lower limb reconstruction . Microsurgery , 31 ( 3 ): 205 - 211 . https://doi.org/10.1002/micr.20841 https://doi.org/10.1002/micr.20841

Bernhard J , Ferguson J , Rieder B , et al. , 2017 . Tissue-engineered hypertrophic chondrocyte grafts enhanced long bone repair . Biomaterials , 139 : 202 - 212 . https://doi.org/10.1016/j.biomaterials.2017.05.045 https://doi.org/10.1016/j.biomaterials.2017.05.045

Bi ZG , Han XG , Fu CJ , et al. , 2008 . Reconstruction of large limb bone defects with a double-barrel free vascularized fibular graft . Chin Med J (Engl) , 121 ( 23 ): 2424 - 2428 .

Bowers KT , Keller JC , Randolph BA , et al. , 1992 . Optimization of surface micromorphology for enhanced osteoblast responses in vitro . Int J Oral Maxillofac Implants , 7 ( 3 ): 302 - 310 .

Boyan BD , Hummert TW , Dean DD , et al. , 1996 . Role of material surfaces in regulating bone and cartilage cell response . Biomaterials , 17 ( 2 ): 137 - 146 . https://doi.org/10.1016/0142-9612(96)85758-9 https://doi.org/10.1016/0142-9612(96)85758-9

Brydone AS , Meek D , Maclaine S , 2010 . Bone grafting, orthopaedic biomaterials, and the clinical need for bone engineering . Proc Inst Mech Eng H , 224 ( 12 ): 1329 - 1343 . https://doi.org/10.1243/09544119JEIM770 https://doi.org/10.1243/09544119JEIM770

Bullens PHJ , Schreuder BHW , de Waal Malefijt MC , et al. , 2009a . Is an impacted morselized graft in a cage an alternative for reconstructing segmental diaphyseal defects? Clin Orthop Relat Res , 467 ( 3 ): 783 - 791 . https://doi.org/10.1007/s11999-008-0686-5 https://doi.org/10.1007/s11999-008-0686-5

Bullens PHJ , Schreuder BHW , de Waal Malefijt MC , et al. , 2009b . The stability of impacted morsellized bone grafts in a metal cage under dynamic loaded conditions: an in vitro reconstruction of a segmental diaphyseal bone defect . Arch Orthop Trauma Surg , 129 ( 5 ): 575 - 581 . https://doi.org/10.1007/s00402-009-0821-0 https://doi.org/10.1007/s00402-009-0821-0

Burke DP , Kelly DJ , 2012 . Substrate stiffness and oxygen as regulators of stem cell differentiation during skeletal tissue regeneration: a mechanobiological model . PLoS ONE , 7 ( 7 ): e40737 . https://doi.org/10.1371/journal.pone.0040737 https://doi.org/10.1371/journal.pone.0040737

Cao H , Kuboyama N , 2010 . A biodegradable porous composite scaffold of PGA/β-TCP for bone tissue engineering . Bone , 46 ( 2 ): 386 - 395 . https://doi.org/10.1016/j.bone.2009.09.031 https://doi.org/10.1016/j.bone.2009.09.031

Capanna R , Campanacci DA , Belot N , et al. , 2007 . A new reconstructive technique for intercalary defects of long bones: the association of massive allograft with vascularized fibular autograft. Long-term results and comparison with alternative techniques . Orthop Clin North Am , 38 ( 1 ): 51 - 60 . https://doi.org/10.1016/j.ocl.2006.10.008 https://doi.org/10.1016/j.ocl.2006.10.008

Carpenter SR , Urits I , Murthi AM , 2016 . Porous metals and alternate bearing surfaces in shoulder arthroplasty . Curr Rev Musculoskelet Med , 9 ( 1 ): 59 - 66 . https://doi.org/10.1007/s12178-016-9319-x https://doi.org/10.1007/s12178-016-9319-x

Ceruso M , Taddei F , Bigazzi P , et al. , 2008 . Vascularised fibula graft inlaid in a massive bone allograft: considerations on the bio-mechanical behaviour of the combined graft in segmental bone reconstructions after sarcoma resection . Injury , 39 ( Suppl 3 ): S68 - S74 . https://doi.org/10.1016/j.injury.2008.05.014 https://doi.org/10.1016/j.injury.2008.05.014

Chen H , Liu Y , Wang CY , et al. , 2021 . Design and properties of biomimetic irregular scaffolds for bone tissue engineering . Comput Biol Med , 130 : 104241 . https://doi.org/10.1016/j.compbiomed.2021.104241 https://doi.org/10.1016/j.compbiomed.2021.104241

Chen K , Xie XH , Tang HY , et al. , 2020 . In vitro and in vivo degradation behavior of Mg-2Sr-Ca and Mg-2Sr-Zn alloys . Bioact Mater , 5 ( 2 ): 275 - 285 . https://doi.org/10.1016/j.bioactmat.2020.02.014 https://doi.org/10.1016/j.bioactmat.2020.02.014

Chen YH , Zhou SW , Li Q , 2011 . Microstructure design of biodegradable scaffold and its effect on tissue regeneration . Biomaterials , 32 ( 22 ): 5003 - 5014 . https://doi.org/10.1016/j.biomaterials.2011.03.064 https://doi.org/10.1016/j.biomaterials.2011.03.064

Cobos JA , Lindsey RW , Gugala Z , 2000 . The cylindrical titanium mesh cage for treatment of a long bone segmental defect: description of a new technique and report of two cases . J Orthop Trauma , 14 ( 1 ): 54 - 59 . https://doi.org/10.1097/00005131-200001000-00011 https://doi.org/10.1097/00005131-200001000-00011

Cooke ME , Ramirez-Garcialuna JL , Rangel-Berridi K , et al. , 2020 . 3D printed polyurethane scaffolds for the repair of bone defects . Front Bioeng Biotechnol , 8 : 557215 . https://doi.org/10.3389/fbioe.2020.557215 https://doi.org/10.3389/fbioe.2020.557215

Cooper DML , Matyas JR , Katzenberg MA , et al. , 2004 . Comparison of microcomputed tomographic and microradiographic measurements of cortical bone porosity . Calcif Tissue Int , 74 ( 5 ): 437 - 447 . https://doi.org/10.1007/s00223-003-0071-z https://doi.org/10.1007/s00223-003-0071-z

de Grado GF , Keller L , Idoux-Gillet Y , et al. , 2018 . Bone substitutes: a review of their characteristics, clinical use, and perspectives for large bone defects management . J Tissue Eng , 9 : 2041731418776819 . https://doi.org/10.1177/2041731418776819 https://doi.org/10.1177/2041731418776819

de Long WG , Einhorn TA , Koval K , et al. , 2007 . Bone grafts and bone graft substitutes in orthopaedic trauma surgery . A critical analysis. J Bone Joint Surg Am , 89 ( 3 ): 649 - 658 . https://doi.org/10.2106/JBJS.F.00465 https://doi.org/10.2106/JBJS.F.00465

Dennis SC , Berkland CJ , Bonewald LF , et al. , 2015 . Endochondral ossification for enhancing bone regeneration: converging native extracellular matrix biomaterials and developmental engineering in vivo . Tissue Eng Part B Rev , 21 ( 3 ): 247 - 266 . https://doi.org/10.1089/ten.TEB.2014.0419 https://doi.org/10.1089/ten.TEB.2014.0419

Dimitriou R , Jones E , McGonagle D , et al. , 2011 . Bone regeneration: current concepts and future directions . BMC Med , 9 : 66 . https://doi.org/10.1186/1741-7015-9-66 https://doi.org/10.1186/1741-7015-9-66

Ding YF , Wen CE , Hodgson P , et al. , 2014 . Effects of alloying elements on the corrosion behavior and biocompatibility of biodegradable magnesium alloys: a review . J Mater Chem B , 2 ( 14 ): 1912 - 1933 . https://doi.org/10.1039/c3tb21746a https://doi.org/10.1039/c3tb21746a

Ding YF , Li YC , Lin JX , et al. , 2015 . Effects of zirconium and strontium on the biocorrosion of Mg-Zr-Sr alloys for biodegradable implant applications . J Mater Chem B , 3 ( 18 ): 3714 - 3729 . https://doi.org/10.1039/c5tb00433k https://doi.org/10.1039/c5tb00433k

Divakarla SK , Yamaguchi S , Kokubo T , et al. , 2018 . Improved bioactivity of gummetal ® : Ti 59 Nb 36 Ta 2 Zr 3 O 0.3 , via formation of nanostructured surfaces . J Tissue Eng , 9 : 2041731418774178 . https://doi.org/10.1177/2041731418774178 https://doi.org/10.1177/2041731418774178

Dong L , Wang SJ , Zhao XR , et al. , 2017 . 3D-printed poly(ε- caprolactone) scaffold integrated with cell-laden chitosan hydrogels for bone tissue engineering. Sci Rep , 7 : 13412 . https://doi.org/10.1038/s41598-017-13838-7 https://doi.org/10.1038/s41598-017-13838-7

Dou HL , Wang GW , Xing N , et al. , 2016 . Repair of large segmental bone defects with fascial flap-wrapped allogeneic bone . J Orthop Surg Res , 11 : 162 . https://doi.org/10.1186/s13018-016-0492-9 https://doi.org/10.1186/s13018-016-0492-9

Dou JH , Zhao YP , Lu L , et al. , 2018 . Effect of the second-step voltages on the structural and corrosion properties of silicon-calcium-phosphate (Si-CaP) coatings on Mg-Zn-Ca alloy . R Soc Open Sci , 5 ( 10 ): 172410 . https://doi.org/10.1098/rsos.172410 https://doi.org/10.1098/rsos.172410

Faia-Torres AB , Guimond-Lischer S , Rottmar M , et al. , 2014 . Differential regulation of osteogenic differentiation of stem cells on surface roughness gradients . Biomaterials , 35 ( 33 ): 9023 - 9032 . https://doi.org/10.1016/j.biomaterials.2014.07.015 https://doi.org/10.1016/j.biomaterials.2014.07.015

Fan JJ , Mu TW , Qin JJ , et al. , 2014 . Different effects of implanting sensory nerve or blood vessel on the vascularization, neurotization, and osteogenesis of tissue-engineered bone in vivo . BioMed Res Int , 2014 : 412570 . https://doi.org/10.1155/2014/412570 https://doi.org/10.1155/2014/412570

Feng XB , Ma L , Liang H , et al. , 2020 . Osteointegration of 3D-printed fully porous polyetheretherketone scaffolds with different pore sizes . ACS Omega , 5 ( 41 ): 26655 - 26666 . https://doi.org/10.1021/acsomega.0c03489 https://doi.org/10.1021/acsomega.0c03489

Feng YF , Wang L , Li X , et al. , 2012 . Influence of architecture of β-tricalcium phosphate scaffolds on biological performance in repairing segmental bone defects . PLoS ONE , 7 ( 11 ): e49955 . https://doi.org/10.1371/journal.pone.0049955 https://doi.org/10.1371/journal.pone.0049955

Fu R , Liu CQ , Yan YX , et al. , 2021 . Bone defect reconstruction via endochondral ossification: a developmental engineering strategy . J Tissue Eng , 12 : 20417314211004211 . https://doi.org/10.1177/20417314211004211 https://doi.org/10.1177/20417314211004211

Ganesh N , Ashokan A , Rajeshkannan R , et al. , 2014 . Magnetic resonance functional nano-hydroxyapatite incorporated poly(caprolactone) composite scaffolds for in situ monitoring of bone tissue regeneration by MRI . Tissue Eng Part A , 20 ( 19-20 ): 2783 - 2794 . https://doi.org/10.1089/ten.TEA.2014.0161 https://doi.org/10.1089/ten.TEA.2014.0161

García-Gareta E , Coathup MJ , Blunn GW , 2015 . Osteoinduction of bone grafting materials for bone repair and regeneration . Bone , 81 : 112 - 121 . https://doi.org/10.1016/j.bone.2015.07.007 https://doi.org/10.1016/j.bone.2015.07.007

Garric X , Nottelet B , Pinese C , et al. , 2017 . Biodegradable synthetic polymers for the design of implantable medical devices: the ligamentoplasty case . Med Sci (Paris) , 33 ( 1 ): 39 - 45 . https://doi.org/10.1051/medsci/20173301007 https://doi.org/10.1051/medsci/20173301007

Gerhardt LC , Boccaccini AR , 2010 . Bioactive glass and glass-ceramic scaffolds for bone tissue engineering . Materials (Basel) , 3 ( 7 ): 3867 - 3910 . https://doi.org/10.3390/ma3073867 https://doi.org/10.3390/ma3073867

Ghayor C , Chen TH , Bhattacharya I , et al. , 2020 . Microporosities in 3D-printed tricalcium-phosphate-based bone substitutes enhance osteoconduction and affect osteoclastic resorption . Int J Mol Sci , 21 ( 23 ): 9270 . https://doi.org/10.3390/ijms21239270 https://doi.org/10.3390/ijms21239270

Giessler GA , Friedrich PF , Shin RH , et al. , 2009 . Healing of free vascularized bone allotransplants: optimizing by short-term immunosuppression and host-derived neovascularization . Unfallchirurg , 112 ( 5 ): 479 - 486 (in German) . https://doi.org/10.1007/s00113-008-1525-6 https://doi.org/10.1007/s00113-008-1525-6

Gosain AK , Song LS , Yu PR , et al. , 2000 . Osteogenesis in cranial defects: reassessment of the concept of critical size and the expression of TGF-β isoforms . Plast Reconstr Surg , 106 ( 2 ): 360 - 371 . https://doi.org/10.1097/00006534-200008000-00018 https://doi.org/10.1097/00006534-200008000-00018

Guo BL , Ma PX , 2014 . Synthetic biodegradable functional polymers for tissue engineering: a brief review . Sci China Chem , 57 ( 4 ): 490 - 500 . https://doi.org/10.1007/s11426-014-5086-y https://doi.org/10.1007/s11426-014-5086-y

Guo XS , Jiang HY , Zong XL , et al. , 2020 . The implication of the notch signaling pathway in biphasic calcium phosphate ceramic-induced ectopic bone formation: a preliminary experiment . J Biomed Mater Res Part A , 108 ( 5 ): 1035 - 1044 . https://doi.org/10.1002/jbm.a.36878 https://doi.org/10.1002/jbm.a.36878

Habibovic P , de Groot K , 2007 . Osteoinductive biomaterials—properties and relevance in bone repair . J Tissue Eng Regen Med , 1 ( 1 ): 25 - 32 . https://doi.org/10.1002/term.5 https://doi.org/10.1002/term.5

Halim AS , Chai SC , Ismail WFW , et al. , 2015 . Long-term outcome of free fibula osteocutaneous flap and massive allograft in the reconstruction of long bone defect . J Plast Reconstr Aesthet Surg , 68 ( 12 ): 1755 - 1762 . https://doi.org/10.1016/j.bjps.2015.08.013 https://doi.org/10.1016/j.bjps.2015.08.013

Hamlekhan A , Moztarzadeh F , Mozafari M , et al. , 2011 . Preparation of laminated poly(ε-caprolactone)-gelatin-hydroxyapatite nanocomposite scaffold bioengineered via compound techniques for bone substitution . Biomatter , 1 ( 1 ): 91 - 101 . https://doi.org/10.4161/biom.1.1.17445 https://doi.org/10.4161/biom.1.1.17445

Han XT , Sharma N , Xu ZQ , et al. , 2019 . An in vitro study of osteoblast response on fused-filament fabrication 3D printed PEEK for dental and cranio-maxillofacial implants . J Clin Med , 8 ( 6 ): 771 . https://doi.org/10.3390/jcm8060771 https://doi.org/10.3390/jcm8060771

Haugen HJ , Lyngstadaas SP , Rossi F , et al. , 2019 . Bone grafts: which is the ideal biomaterial? J Clin Periodontol , 46 ( Suppl 21 ): 92 - 102 . https://doi.org/10.1111/jcpe.13058 https://doi.org/10.1111/jcpe.13058

Hayashi K , Kishida R , Tsuchiya A , et al. , 2019 . Carbonate apatite micro-honeycombed blocks generate bone marrow-like tissues as well as bone . Adv Biosyst , 3 ( 12 ): 1900140 . https://doi.org/10.1002/adbi.201900140 https://doi.org/10.1002/adbi.201900140

He B , Ou YS , Zhou A , et al. , 2016 . Functionalized D-form self-assembling peptide hydrogels for bone regeneration . Drug Des Devel Ther , 10 : 1379 - 1388 . https://doi.org/10.2147/DDDT.S97530 https://doi.org/10.2147/DDDT.S97530

Henkel J , Woodruff MA , Epari DR , et al. , 2013 . Bone regeneration based on tissue engineering conceptions—a 21st century perspective . Bone Res , 1 ( 3 ): 216 - 248 . https://doi.org/10.4248/BR201303002 https://doi.org/10.4248/BR201303002

Hollinger JO , Kleinschmidt JC , 1990 . The critical size defect as an experimental model to test bone repair materials . J Craniofac Surg , 1 ( 1 ): 60 - 68 . https://doi.org/10.1097/00001665-199001000-00011 https://doi.org/10.1097/00001665-199001000-00011

Hu YP , Dong DL , Wang XY , et al. , 2021 . Synthesis and properties of Mg-Mn-Zn alloys for medical applications . Materials (Basel) , 14 ( 8 ): 1855 . https://doi.org/10.3390/ma14081855 https://doi.org/10.3390/ma14081855

Hulbert SF , Young FA , Mathews RS , et al. , 1970 . Potential of ceramic materials as permanently implantable skeletal prostheses . J Biomed Mater Res , 4 ( 3 ): 433 - 456 . https://doi.org/10.1002/jbm.820040309 https://doi.org/10.1002/jbm.820040309

Hutmacher DW , Schantz JT , Lam CXF , et al. , 2007 . State of the art and future directions of scaffold-based bone engineering from a biomaterials perspective . J Tissue Eng Regen Med , 1 ( 4 ): 245 - 260 . https://doi.org/10.1002/term.24 https://doi.org/10.1002/term.24

Innocenti M , Abed YY , Beltrami G , et al. , 2009 . Biological reconstruction after resection of bone tumors of the proximal tibia using allograft shell and intramedullary free vascularized fibular graft: long-term results . Microsurgery , 29 ( 5 ): 361 - 372 . https://doi.org/10.1002/micr.20668 https://doi.org/10.1002/micr.20668

James J , Steijn-Myagkaya GL , 1986 . Death of osteocytes. Electron microscopy after in vitro ischaemia . J Bone Joint Surg Br , 68 ( 4 ): 620 - 624 . https://doi.org/10.1302/0301-620X.68B4.3733842 https://doi.org/10.1302/0301-620X.68B4.3733842

Jeong J , Kim JH , Shim JH , et al. , 2019 . Bioactive calcium phosphate materials and applications in bone regeneration . Biomater Res , 23 : 4 . https://doi.org/10.1186/s40824-018-0149-3 https://doi.org/10.1186/s40824-018-0149-3

Ji Y , Hou MD , Zhang J , et al. , 2022 . Preparation and properties of partial-degradable ZrO 2 -chitosan particles-GeLMA composite scaffolds . Polymers (Basel) , 14 ( 19 ): 4233 . https://doi.org/10.3390/polym14194233 https://doi.org/10.3390/polym14194233

Kanczler JM , Oreffo ROC , 2008 . Osteogenesis and angiogenesis: the potential for engineering bone . Eur Cell Mater , 15 : 100 - 114 . https://doi.org/10.22203/ecm.v015a08 https://doi.org/10.22203/ecm.v015a08

Karageorgiou V , Kaplan D , 2005 . Porosity of 3D biomaterial scaffolds and osteogenesis . Biomaterials , 26 ( 27 ): 5474 - 5491 . https://doi.org/10.1016/j.biomaterials.2005.02.002 https://doi.org/10.1016/j.biomaterials.2005.02.002

Kawasaki S , Inagaki Y , Akahane M , et al. , 2020 . In vitro osteogenesis of rat bone marrow mesenchymal cells on peek disks with heat-fixed apatite by CO 2 laser bonding . BMC Musculoskelet Disord , 21 : 692 . https://doi.org/10.1186/s12891-020-03716-1 https://doi.org/10.1186/s12891-020-03716-1

Kawate K , Yajima H , Sugimoto K , et al. , 2007 . Indications for free vascularized fibular grafting for the treatment of osteonecrosis of the femoral head . BMC Musculoskelet Disord , 8 : 78 . https://doi.org/10.1186/1471-2474-8-78 https://doi.org/10.1186/1471-2474-8-78

Khan FSA , Mubarak NM , Khalid M , et al. , 2021 . Functionalized multi-walled carbon nanotubes and hydroxyapatite nanorods reinforced with polypropylene for biomedical application . Sci Rep , 11 : 843 . https://doi.org/10.1038/s41598-020-80767-3 https://doi.org/10.1038/s41598-020-80767-3

Khira YM , Badawy HA , 2013 . Pedicled vascularized fibular graft with ilizarov external fixator for reconstructing a large bone defect of the tibia after tumor resection . J Orthop Traumatol , 14 ( 2 ): 91 - 100 . https://doi.org/10.1007/s10195-013-0225-3 https://doi.org/10.1007/s10195-013-0225-3

Kim BS , Kim JS , Yang SS , et al. , 2015 . Angiogenin-loaded fibrin/bone powder composite scaffold for vascularized bone regeneration . Biomater Res , 19 : 18 . https://doi.org/10.1186/s40824-015-0040-4 https://doi.org/10.1186/s40824-015-0040-4

Kim HS , Kumbar SG , Nukavarapu SP , 2021 . Biomaterial-directed cell behavior for tissue engineering . Curr Opin Biomed Eng , 17 : 100260 . https://doi.org/10.1016/j.cobme.2020.100260 https://doi.org/10.1016/j.cobme.2020.100260

Kim KM , Kim HY , Miyazaki S , 2020 . Effect of Zr content on phase stability, deformation behavior, and Young’s modulus in Ti-Nb-Zr alloys . Materials (Basel) , 13 ( 2 ): 476 . https://doi.org/10.3390/ma13020476 https://doi.org/10.3390/ma13020476

Kim SY , Bae EB , Huh JW , et al. , 2019 . Bone regeneration using a three-dimensional hexahedron channeled BCP block combined with bone morphogenic protein-2 in rat calvarial defects . Materials (Basel) , 12 ( 15 ): 2435 . https://doi.org/10.3390/ma12152435 https://doi.org/10.3390/ma12152435

Klijn RJ , Meijer GJ , Bronkhorst EM , et al. , 2010 . A meta-analysis of histomorphometric results and graft healing time of various biomaterials compared to autologous bone used as sinus floor augmentation material in humans . Tissue Eng Part B Rev , 16 ( 5 ): 493 - 507 . https://doi.org/10.1089/ten.TEB.2010.0035 https://doi.org/10.1089/ten.TEB.2010.0035

Knuth C , Kiernan C , Wolvius E , et al. , 2019 . Understanding tissue-engineered endochondral ossification; Towards improved bone formation . Eur Cell Mater , 37 : 277 - 291 . https://doi.org/10.22203/eCM.v037a17 https://doi.org/10.22203/eCM.v037a17

Ko HS , Lee S , Jho JY , 2021 . Synthesis and modification of hydroxyapatite nanofiber for poly(lactic acid) composites with enhanced mechanical strength and bioactivity . Nanomaterials (Basel) , 11 ( 1 ): 213 . https://doi.org/10.3390/nano11010213 https://doi.org/10.3390/nano11010213

Kogawa M , Khalid KA , Wijenayaka AR , et al. , 2018 . Recombinant sclerostin antagonizes effects of ex vivo mechanical loading in trabecular bone and increases osteocyte lacunar size . Am J Physiol Cell Physiol , 314 ( 1 ): C53 - C61 . https://doi.org/10.1152/ajpcell.00175.2017 https://doi.org/10.1152/ajpcell.00175.2017

Kohli N , Sharma V , Orera A , et al. , 2021 . Pro-angiogenic and osteogenic composite scaffolds of fibrin, alginate and calcium phosphate for bone tissue engineering . J Tissue Eng , 12 : 20417314211005610 . https://doi.org/10.1177/20417314211005610 https://doi.org/10.1177/20417314211005610

Kolk A , Handschel J , Drescher W , et al. , 2012 . Current trends and future perspectives of bone substitute materials ‒ from space holders to innovative biomaterials . J Craniomaxillofac Surg , 40 ( 8 ): 706 - 718 . https://doi.org/10.1016/j.jcms.2012.01.002 https://doi.org/10.1016/j.jcms.2012.01.002

Korompilias AV , Paschos NK , Lykissas MG , et al. , 2011 . Recent updates of surgical techniques and applications of free vascularized fibular graft in extremity and trunk reconstruction . Microsurgery , 31 ( 3 ): 171 - 175 . https://doi.org/10.1002/micr.20848 https://doi.org/10.1002/micr.20848

Kovoor CC , Jayakumar R , George VV , et al. , 2011 . Vascularized fibular graft in infected tibial bone loss . Indian J Orthop , 45 ( 4 ): 330 - 335 . https://doi.org/10.4103/0019-5413.82337 https://doi.org/10.4103/0019-5413.82337

Kunii T , Mori Y , Tanaka H , et al. , 2019 . Improved osseointegration of a TiNbSn alloy with a low Young’s modulus treated with anodic oxidation . Sci Rep , 9 : 13985 . https://doi.org/10.1038/s41598-019-50581-7 https://doi.org/10.1038/s41598-019-50581-7

Lee DJ , Lee YT , Zou R , et al. , 2017 . Polydopamine-laced biomimetic material stimulation of bone marrow derived mesenchymal stem cells to promote osteogenic effects . Sci Rep , 7 : 12984 . https://doi.org/10.1038/s41598-017-13326-y https://doi.org/10.1038/s41598-017-13326-y

Levengood SKL , Polak SJ , Wheeler MB , et al. , 2010 . Multiscale osteointegration as a new paradigm for the design of calcium phosphate scaffolds for bone regeneration . Biomaterials , 31 ( 13 ): 3552 - 3563 . https://doi.org/10.1016/j.biomaterials.2010.01.052 https://doi.org/10.1016/j.biomaterials.2010.01.052

Li HY , Xue K , Kong N , et al. , 2014 . Silicate bioceramics enhanced vascularization and osteogenesis through stimulating interactions between endothelia cells and bone marrow stromal cells . Biomaterials , 35 ( 12 ): 3803 - 3818 . https://doi.org/10.1016/j.biomaterials.2014.01.039 https://doi.org/10.1016/j.biomaterials.2014.01.039

Li JJ , Gil ES , Hayden RS , et al. , 2013 . Multiple silk coatings on biphasic calcium phosphate scaffolds: effect on physical and mechanical properties and in vitro osteogenic response of human mesenchymal stem cells . Biomacromolecules , 14 ( 7 ): 2179 - 2188 . https://doi.org/10.1021/bm400303w https://doi.org/10.1021/bm400303w

Li JP , de Wijn JR , van Blitterswijk CA , et al. , 2006 . Porous Ti 6 Al 4 V scaffold directly fabricating by rapid prototyping: preparation and in vitro experim ent . Biomaterials , 27 ( 8 ): 1223 - 1235 . https://doi.org/10.1016/j.biomaterials.2005.08.033 https://doi.org/10.1016/j.biomaterials.2005.08.033

Lin CH , Wei FC , Chen HC , et al. , 1999 . Outcome comparison in traumatic lower-extremity reconstruction by using various composite vascularized bone transplantation . Plast Reconstr Surg , 104 ( 4 ): 984 - 992 . https://doi.org/10.1097/00006534-199909040-00013 https://doi.org/10.1097/00006534-199909040-00013

Linder HR , Glass AA , Day DE , et al. , 2020 . Manipulating air-gap electrospinning to create aligned polymer nanofiber-wrapped glass microfibers for cortical bone tissue engineering . Bioengineering (Basel) , 7 ( 4 ): 165 . https://doi.org/10.3390/bioengineering7040165 https://doi.org/10.3390/bioengineering7040165

Lindsey RW , Gugala Z , Milne E , et al. , 2006 . The efficacy of cylindrical titanium mesh cage for the reconstruction of a critical-size canine segmental femoral diaphyseal defect . J Orthop Res , 24 ( 7 ): 1438 - 1453 . https://doi.org/10.1002/jor.20154 https://doi.org/10.1002/jor.20154

Long M , Rack HJ , 1998 . Titanium alloys in total joint replacement—a materials science perspective . Biomaterials , 19 ( 18 ): 1621 - 1639 . https://doi.org/10.1016/s0142-9612(97)00146-4 https://doi.org/10.1016/s0142-9612(97)00146-4

Ma HS , Feng C , Chang J , et al. , 2018 . 3D-printed bioceramic scaffolds: from bone tissue engineering to tumor therapy . Acta Biomater , 79 : 37 - 59 . https://doi.org/10.1016/j.actbio.2018.08.026 https://doi.org/10.1016/j.actbio.2018.08.026

Ma QL , Miri Z , Haugen HJ , et al. , 2023 . Significance of mechanical loading in bone fracture healing, bone regeneration, and vascularization . J Tissue Eng , 14 : 20417314231172573 . https://doi.org/10.1177/20417314231172573 https://doi.org/10.1177/20417314231172573

Ma YH , Gu SJ , Yin QD , et al. , 2019 . Application of multiple wrapped cancellous bone graft methods for treatment of segmental bone defects . BMC Musculoskelet Disord , 20 : 346 . https://doi.org/10.1186/s12891-019-2713-y https://doi.org/10.1186/s12891-019-2713-y

Manfrini M , Bindiganavile S , Say F , et al. , 2017 . Is there benefit to free over pedicled vascularized grafts in augmenting tibial intercalary allograft constructs? Clin Orthop Relat Res , 475 ( 5 ): 1322 - 1337 . https://doi.org/10.1007/s11999-016-5196-2 https://doi.org/10.1007/s11999-016-5196-2

Maradze D , Musson D , Zheng YF , et al. , 2018 . High magnesium corrosion rate has an effect on osteoclast and mesenchymal stem cell role during bone remodelling . Sci Rep , 8 : 10003 . https://doi.org/10.1038/s41598-018-28476-w https://doi.org/10.1038/s41598-018-28476-w

Marí-Buyé N , Luque T , Navajas D , et al. , 2013 . Development of a three-dimensional bone-like construct in a soft self-assembling peptide matrix . Tissue Eng Part A , 19 ( 7-8 ): 870 - 881 . https://doi.org/10.1089/ten.TEA.2012.0077 https://doi.org/10.1089/ten.TEA.2012.0077

Marín JAT , Londoño SR , Delgado J , et al. , 2019 . Biocompatible and antimicrobial electrospun membranes based on nanocomposites of chitosan/poly (vinyl alcohol)/graphene oxide . Int J Mol Sci , 20 ( 12 ): 2987 . https://doi.org/10.3390/ijms20122987 https://doi.org/10.3390/ijms20122987

Marrella A , Lee TY , Lee DH , et al. , 2018 . Engineering vascularized and innervated bone biomaterials for improved skeletal tissue regeneration . Mater Today (Kidlington) , 21 ( 4 ): 362 - 376 . https://doi.org/10.1016/j.mattod.2017.10.005 https://doi.org/10.1016/j.mattod.2017.10.005

Martin RB , 1991 . Determinants of the mechanical properties of bones . J Biomech , 24 ( Suppl 1 ): 79 - 88 . https://doi.org/10.1016/0021-9290(91)90379-2 https://doi.org/10.1016/0021-9290(91)90379-2

Miri Z , Haugen HJ , Loca D , et al. , 2024 . Review on the strategies to improve the mechanical strength of highly porous bone bioceramic scaffolds . J Eur Ceram Soc , 44 ( 1 ): 23 - 42 . https://doi.org/10.1016/j.jeurceramsoc.2023.09.003 https://doi.org/10.1016/j.jeurceramsoc.2023.09.003

Momesso GAC , de Souza Santos A , Santos JMFE , et al. , 2020 . Comparison between plasma electrolytic oxidation coating and sandblasted acid-etched surface treatment: histometric, tomographic, and expression levels of osteoclastogenic factors in osteoporotic rats . Materials (Basel) , 13 ( 7 ): 1604 . https://doi.org/10.3390/ma13071604 https://doi.org/10.3390/ma13071604

Morgan EF , Unnikrisnan GU , Hussein AI , 2018 . Bone mechanical properties in healthy and diseased states . Annu Rev Biomed Eng , 20 : 119 - 143 . https://doi.org/10.1146/annurev-bioeng-062117-121139 https://doi.org/10.1146/annurev-bioeng-062117-121139

Mui KL , Chen CS , Assoian RK , 2016 . The mechanical regulation of integrin-cadherin crosstalk organizes cells, signaling and forces . J Cell Sci , 129 ( 6 ): 1093 - 1100 . https://doi.org/10.1242/jcs.183699 https://doi.org/10.1242/jcs.183699

Murshed M , Harmey D , Millán JL , et al. , 2005 . Unique coexpression in osteoblasts of broadly expressed genes accounts for the spatial restriction of ECM mineralization to bone . Genes Dev , 19 ( 9 ): 1093 - 1104 . https://doi.org/10.1101/gad.1276205 https://doi.org/10.1101/gad.1276205

Nikpour P , Salimi-Kenari H , Fahimipour F , et al. , 2018 . Dextran hydrogels incorporated with bioactive glass-ceramic: nanocomposite scaffolds for bone tissue engineering . Carbohydr Polym , 190 : 281 - 294 . https://doi.org/10.1016/j.carbpol.2018.02.083 https://doi.org/10.1016/j.carbpol.2018.02.083

No YJ , Li JJ , Zreiqat H , 2017 . Doped calcium silicate ceramics: a new class of candidates for synthetic bone substitutes . Materials (Basel) , 10 ( 2 ): 153 . https://doi.org/10.3390/ma10020153 https://doi.org/10.3390/ma10020153

Noyama Y , Nakano T , Ishimoto T , et al. , 2013 . Design and optimization of the oriented groove on the hip implant surface to promote bone microstructure integrity . Bone , 52 ( 2 ): 659 - 667 . https://doi.org/10.1016/j.bone.2012.11.005 https://doi.org/10.1016/j.bone.2012.11.005

Ogilvie CM , Crawford EA , Hosalkar HS , et al. , 2009 . Long-term results for limb salvage with osteoarticular allograft reconstruction . Clin Orthop Relat Res , 467 ( 10 ): 2685 - 2690 . https://doi.org/10.1007/s11999-009-0726-9 https://doi.org/10.1007/s11999-009-0726-9

Ou QF , Wu PF , Zhou ZB , et al. , 2020 . Complication of osteo reconstruction by utilizing free vascularized fibular bone graft . BMC Surg , 20 : 216 . https://doi.org/10.1186/s12893-020-00875-9 https://doi.org/10.1186/s12893-020-00875-9

Ozaki T , Hillmann A , Wuisman P , et al. , 1997 . Reconstruction of tibia by ipsilateral vascularized fibula and allograft: 12 cases with malignant bone tumors . Acta Orthop Scand , 68 ( 3 ): 298 - 301 . https://doi.org/10.3109/17453679708996706 https://doi.org/10.3109/17453679708996706

Patel DK , Jin B , Dutta SD , et al. , 2020 . Osteogenic potential of human mesenchymal stem cells on eggshells-derived hydroxyapatite nanoparticles for tissue engineering . J Biomed Mater Res Part B Appl Biomater , 108 ( 5 ): 1953 - 1960 . https://doi.org/10.1002/jbm.b.34536 https://doi.org/10.1002/jbm.b.34536

Pederson WC , Person DW , 2007 . Long bone reconstruction with vascularized bone grafts . Orthop Clin North Am , 38 ( 1 ): 23 - 35 . https://doi.org/10.1016/j.ocl.2006.10.006 https://doi.org/10.1016/j.ocl.2006.10.006

Perier-Metz C , Duda GN , Checa S , 2021 . Initial mechanical conditions within an optimized bone scaffold do not ensure bone regeneration―an in silico analysis . Biomech Model Mechanobiol , 20 ( 5 ): 1723 - 1731 . https://doi.org/10.1007/s10237-021-01472-2 https://doi.org/10.1007/s10237-021-01472-2

Pitacco P , Sadowska JM , O'Brien FJ , et al. , 2023 . 3D bioprinting of cartilaginous templates for large bone defect healing . Acta Biomater , 156 : 61 - 74 . https://doi.org/10.1016/j.actbio.2022.07.037 https://doi.org/10.1016/j.actbio.2022.07.037

Prithivirajan S , Nyahale MB , Naik GM , et al. , 2021 . Bio-corrosion impacts on mechanical integrity of ZM21 Mg for orthopaedic implant application processed by equal channel angular pressing . J Mater Sci Mater Med , 32 ( 6 ): 65 . https://doi.org/10.1007/s10856-021-06535-5 https://doi.org/10.1007/s10856-021-06535-5

Rabitsch K , Maurer-Ertl W , Pirker-Frühauf U , et al. , 2013 . Intercalary reconstructions with vascularised fibula and allograft after tumour resection in the lower limb . Sarcoma , 2013 : 160295 . https://doi.org/10.1155/2013/160295 https://doi.org/10.1155/2013/160295

Reichert JC , Wullschleger ME , Cipitria A , et al. , 2011 . Custom-made composite scaffolds for segmental defect repair in long bones . Int Orthop , 35 ( 8 ): 1229 - 1236 . https://doi.org/10.1007/s00264-010-1146-x https://doi.org/10.1007/s00264-010-1146-x

Roddy E , DeBaun MR , Daoud-Gray A , et al. , 2018 . Treatment of critical-sized bone defects: clinical and tissue engineering perspectives . Eur J Orthop Surg Traumatol , 28 ( 3 ): 351 - 362 . https://doi.org/10.1007/s00590-017-2063-0 https://doi.org/10.1007/s00590-017-2063-0

Rodríguez-Montaño OL , Cortés-Rodríguez CJ , Naddeo F , et al. , 2019 . Irregular load adapted scaffold optimization: a computational framework based on mechanobiological criteria . ACS Biomater Sci Eng , 5 ( 10 ): 5392 - 5411 . https://doi.org/10.1021/acsbiomaterials.9b01023 https://doi.org/10.1021/acsbiomaterials.9b01023

Rouwkema J , Khademhosseini A , 2016 . Vascularization and angiogenesis in tissue engineering: beyond creating static networks . Trends Biotechnol , 34 ( 9 ): 733 - 745 . https://doi.org/10.1016/j.tibtech.2016.03.002 https://doi.org/10.1016/j.tibtech.2016.03.002

Rouwkema J , Rivron NC , van Blitterswijk CA , 2008 . Vascularization in tissue engineering . Trends Biotechnol , 26 ( 8 ): 434 - 441 . https://doi.org/10.1016/j.tibtech.2008.04.009 https://doi.org/10.1016/j.tibtech.2008.04.009

Salgado AJ , Coutinho OP , Reis RL , 2004 . Bone tissue engineering: state of the art and future trends . Macromol Biosci , 4 ( 8 ): 743 - 765 . https://doi.org/10.1002/mabi.200400026 https://doi.org/10.1002/mabi.200400026

Santos MI , Reis RL , 2010 . Vascularization in bone tissue engineering: physiology, current strategies, major hurdles and future challenges . Macromol Biosci , 10 ( 1 ): 12 - 27 . https://doi.org/10.1002/mabi.200900107 https://doi.org/10.1002/mabi.200900107

Saruta J , Sato N , Ishijima M , et al. , 2019 . Disproportionate effect of sub-micron topography on osteoconductive capability of titanium . Int J Mol Sci , 20 ( 16 ): 4027 . https://doi.org/10.3390/ijms20164027 https://doi.org/10.3390/ijms20164027

Schmitz JP , Hollinger JO , 1986 . The critical size defect as an experimental model for craniomandibulofacial nonunions . Clin Orthop Relat Res , ( 205 ): 299 - 308 .

Sen MK , Miclau T , 2007 . Autologous iliac crest bone graft: should it still be the gold standard for treating nonunions? Injury , 38 ( Suppl 1 ): S75 - S80 . https://doi.org/10.1016/j.injury.2007.02.012 https://doi.org/10.1016/j.injury.2007.02.012

Shen MK , Wang LL , Gao Y , et al. , 2022 . 3D bioprinting of in situ vascularized tissue engineered bone for repairing large segmental bone defects . Mater Today Bio , 16 : 100382 . https://doi.org/10.1016/j.mtbio.2022.100382 https://doi.org/10.1016/j.mtbio.2022.100382

Shi JP , Zhu LY , Li L , et al. , 2018 . A TPMS-based method for modeling porous scaffolds for bionic bone tissue engineering . Sci Rep , 8 : 7395 . https://doi.org/10.1038/s41598-018-25750-9 https://doi.org/10.1038/s41598-018-25750-9

Shibahara K , Hayashi K , Nakashima Y , et al. , 2022 . Effects of channels and micropores in honeycomb scaffolds on the reconstruction of segmental bone defects . Front Bioeng Biotechnol , 10 : 825831 . https://doi.org/10.3389/fbioe.2022.825831 https://doi.org/10.3389/fbioe.2022.825831

Song GL , 2007 . Control of biodegradation of biocompatable magnesium alloys . Corros Sci , 49 ( 4 ): 1696 - 1701 . https://doi.org/10.1016/j.corsci.2007.01.001 https://doi.org/10.1016/j.corsci.2007.01.001

Stahl A , Yang YP , 2021 . Regenerative approaches for the treatment of large bone defects . Tissue Eng Part B Rev , 27 ( 6 ): 539 - 547 . https://doi.org/10.1089/ten.TEB.2020.0281 https://doi.org/10.1089/ten.TEB.2020.0281

Su X , Wang T , Guo S , 2021 . Applications of 3D printed bone tissue engineering scaffolds in the stem cell field . Regen Ther , 16 : 63 - 72 . https://doi.org/10.1016/j.reth.2021.01.007 https://doi.org/10.1016/j.reth.2021.01.007

Sun WZ , Ye B , Chen SY , et al. , 2023 . Neuro-bone tissue engineering: emerging mechanisms, potential strategies, and current challenges . Bone Res , 11 : 65 . https://doi.org/10.1038/s41413-023-00302-8 https://doi.org/10.1038/s41413-023-00302-8

Szostakowski B , DeMaio M , 2020 . Ideal xenograft or a perfect bone substitute?—A retrospective review and analysis of the historical concept of ivory implants in orthopaedics . Int Orthop , 44 ( 5 ): 1003 - 1009 . https://doi.org/10.1007/s00264-020-04483-3 https://doi.org/10.1007/s00264-020-04483-3

Tansik G , Kilic E , Beter M , et al. , 2016 . A glycosaminoglycan mimetic peptide nanofiber gel as an osteoinductive scaffold . Biomater Sci , 4 ( 9 ): 1328 - 1339 . https://doi.org/10.1039/c6bm00179c https://doi.org/10.1039/c6bm00179c

Tarafder S , Davies NM , Bandyopadhyay A , et al. , 2013 . 3D printed tricalcium phosphate bone tissue engineering scaffolds: effect of SrO and MgO doping on in vivo osteogenesis in a rat distal femoral defect model . Biomater Sci , 1 ( 12 ): 1250 - 1259 . https://doi.org/10.1039/C3BM60132C https://doi.org/10.1039/C3BM60132C

Thompson EM , Matsiko A , Farrell E , et al. , 2015 . Recapitulating endochondral ossification: a promising route to in vivo bone regeneration . J Tissue Eng Regen Med , 9 ( 8 ): 889 - 902 . https://doi.org/10.1002/term.1918 https://doi.org/10.1002/term.1918

Tian T , Xie WH , Gao WD , et al. , 2019 . Micro-nano bioactive glass particles incorporated porous scaffold for promoting osteogenesis and angiogenesis in vitro . Front Chem , 7 : 186 . https://doi.org/10.3389/fchem.2019.00186 https://doi.org/10.3389/fchem.2019.00186

Toworfe GK , Composto RJ , Lee MH , et al. , 2010 . Elastic membrane that undergoes mechanical deformation enhances osteoblast cellular attachment and proliferation . Int J Biomater , 2010 : 947232 . https://doi.org/10.1155/2010/947232 https://doi.org/10.1155/2010/947232

Unagolla JM , Jayasuriya AC , 2019 . Enhanced cell functions on graphene oxide incorporated 3D printed polycaprolactone scaffolds . Mater Sci Eng C , 102 : 1 - 11 . https://doi.org/10.1016/j.msec.2019.04.026 https://doi.org/10.1016/j.msec.2019.04.026

Venkatramani H , Sabapathy SR , Dheenadayalan J , et al. , 2015 . Reconstruction of post-traumatic long segment bone defects of the lower end of the femur by free vascularized fibula combined with allograft (modified Capanna’s technique) . Eur J Trauma Emerg Surg , 41 ( 1 ): 17 - 24 . https://doi.org/10.1007/s00068-014-0451-2 https://doi.org/10.1007/s00068-014-0451-2

von Erlach TC , Bertazzo S , Wozniak MA , et al. , 2018 . Cell-geometry-dependent changes in plasma membrane order direct stem cell signalling and fate . Nat Mater , 17 ( 3 ): 237 - 242 . https://doi.org/10.1038/s41563-017-0014-0 https://doi.org/10.1038/s41563-017-0014-0

Wahyuningtyas E , Hsu LC , Lan WC , et al. , 2019 . Application of a promising bone graft substitute in bone tissue regeneration: characterization, biocompatibility, and in vivo animal study . BioMed Res Int , 2019 : 1614024 . https://doi.org/10.1155/2019/1614024 https://doi.org/10.1155/2019/1614024

Wan T , Jiao ZX , Guo M , et al. , 2020 . Gaseous sulfur trioxide induced controllable sulfonation promoting biomineralization and osseointegration of polyetheretherketone implants . Bioact Mater , 5 ( 4 ): 1004 - 1017 . https://doi.org/10.1016/j.bioactmat.2020.06.011 https://doi.org/10.1016/j.bioactmat.2020.06.011

Wang GJ , Shen LD , Zhao JF , et al. , 2018 . Design and compressive behavior of controllable irregular porous scaffolds: based on Voronoi-Tessellation and for additive manufacturing . ACS Biomater Sci Eng , 4 ( 2 ): 719 - 727 . https://doi.org/10.1021/acsbiomaterials.7b00916 https://doi.org/10.1021/acsbiomaterials.7b00916

Wang L , Fan HB , Zhang ZY , et al. , 2010 . Osteogenesis and angiogenesis of tissue-engineered bone constructed by prevascularized β-tricalcium phosphate scaffold and mesenchymal stem cells . Biomaterials , 31 ( 36 ): 9452 - 9461 . https://doi.org/10.1016/j.biomaterials.2010.08.036 https://doi.org/10.1016/j.biomaterials.2010.08.036

Wang R , Ni SL , Ma L , et al. , 2022 . Porous construction and surface modification of titanium-based materials for osteogenesis: a review . Front Bioeng Biotechnol , 10 : 973297 . https://doi.org/10.3389/fbioe.2022.973297 https://doi.org/10.3389/fbioe.2022.973297

Wang XD , Li SY , Zhang SJ , et al. , 2020 . The neural system regulates bone homeostasis via mesenchymal stem cells: a translational approach . Theranostics , 10 ( 11 ): 4839 - 4850 . https://doi.org/10.7150/thno.43771 https://doi.org/10.7150/thno.43771

Wang XH , Su N , 2021 . Neurokinin-1-tachykinin receptor agonist promotes diabetic fracture healing in rats with type 1 diabetes via modulation of Wnt/β-catenin signalling axis . Saudi J Biol Sci , 28 ( 4 ): 2139 - 2145 . https://doi.org/10.1016/j.sjbs.2021.02.026 https://doi.org/10.1016/j.sjbs.2021.02.026

Wang YF , Zhang W , Yao QQ , 2021 . Copper-based biomaterials for bone and cartilage tissue engineering . J Orthop Translat , 29 : 60 - 71 . https://doi.org/10.1016/j.jot.2021.03.003 https://doi.org/10.1016/j.jot.2021.03.003

Winkler T , Sass FA , Duda GN , et al. , 2018 . A review of biomaterials in bone defect healing, remaining shortcomings and future opportunities for bone tissue engineering: the unsolved challenge . Bone Joint Res , 7 ( 3 ): 232 - 243 . https://doi.org/10.1302/2046-3758.73.BJR-2017-0270.R1 https://doi.org/10.1302/2046-3758.73.BJR-2017-0270.R1

Woodard JR , Hilldore AJ , Lan SK , et al. , 2007 . The mechanical properties and osteoconductivity of hydroxyapatite bone scaffolds with multi-scale porosity . Biomaterials , 28 ( 1 ): 45 - 54 . https://doi.org/10.1016/j.biomaterials.2006.08.021 https://doi.org/10.1016/j.biomaterials.2006.08.021

Wu C , Fang JG , Entezari A , et al. , 2021 . A time-dependent mechanobiology-based topology optimization to enhance bone growth in tissue scaffolds . J Biomech , 117 : 110233 . https://doi.org/10.1016/j.jbiomech.2021.110233 https://doi.org/10.1016/j.jbiomech.2021.110233

Wu Y , Jing D , Ouyang HW , et al. , 2015 . Pre-implanted sensory nerve could enhance the neurotization in tissue-engineered bone graft . Tissue Eng Part A , 21 ( 15-16 ): 2241 - 2249 . https://doi.org/10.1089/ten.TEA.2014.0688 https://doi.org/10.1089/ten.TEA.2014.0688

Xiao DQ , Zhang JW , Zhang CD , et al. , 2020 . The role of calcium phosphate surface structure in osteogenesis and the mechanisms involved . Acta Biomater , 106 : 22 - 33 . https://doi.org/10.1016/j.actbio.2019.12.034 https://doi.org/10.1016/j.actbio.2019.12.034

Xie YL , Sun WC , Yan FF , et al. , 2019 . Icariin-loaded porous scaffolds for bone regeneration through the regulation of the coupling process of osteogenesis and osteoclastic activity . Int J Nanomedicine , 14 : 6019 - 6033 . https://doi.org/10.2147/IJN.S203859 https://doi.org/10.2147/IJN.S203859

Xu J , Hu XY , Jiang SY , et al. , 2019 . The application of multi-walled carbon nanotubes in bone tissue repair hybrid scaffolds and the effect on cell growth in vitro . Polymers (Basel) , 11 ( 2 ): 230 . https://doi.org/10.3390/polym11020230 https://doi.org/10.3390/polym11020230

Xu YY , Hu YY , Liu CY , et al. , 2018 . A novel strategy for creating tissue-engineered biomimetic blood vessels using 3D bioprinting technology . Materials (Basel) , 11 ( 9 ): 1581 . https://doi.org/10.3390/ma11091581 https://doi.org/10.3390/ma11091581

Yazdanpanah Z , Johnston JD , Cooper DML , et al. , 2022 . 3D bioprinted scaffolds for bone tissue engineering: state-of-the-art and emerging technologies . Front Bioeng Biotechnol , 10 : 824156 . https://doi.org/10.3389/fbioe.2022.824156 https://doi.org/10.3389/fbioe.2022.824156

Yu JM , Li K , Zheng XB , et al. , 2013 . In vitro and in vivo evaluation of zinc-modified Ca-Si-based ceramic coating for bone implants . PLoS ONE , 8 ( 3 ): e57564 . https://doi.org/10.1371/journal.pone.0057564 https://doi.org/10.1371/journal.pone.0057564

Yuan B , Zhang YX , Zhao R , et al. , 2022 . A unique biomimetic modification endows polyetherketoneketone scaffold with osteoinductivity by activating cAMP/PKA signaling pathway . Sci Adv , 8 ( 40 ): eabq7116 . https://doi.org/10.1126/sciadv.abq7116 https://doi.org/10.1126/sciadv.abq7116

Zekry KM , Yamamoto N , Hayashi K , et al. , 2019 . Reconstruction of intercalary bone defect after resection of malignant bone tumor . J Orthop Surg (Hong Kong) , 27 ( 1 ): 2309499019832970 . https://doi.org/10.1177/2309499019832970 https://doi.org/10.1177/2309499019832970

Zhai PS , Peng XX , Li BQ , et al. , 2020 . The application of hyaluronic acid in bone regeneration . Int J Biol Macromol , 151 : 1224 - 1239 . https://doi.org/10.1016/j.ijbiomac.2019.10.169 https://doi.org/10.1016/j.ijbiomac.2019.10.169

Zhang B , Zhang PB , Wang ZL , et al. , 2017 . Tissue-engineered composite scaffold of poly and hydroxyapatite nanoparticles seeded with autologous mesenchymal stem cells for bone regeneration . J Zhejiang Univ-Sci B (Biomed & Biotechnol) , 18 ( 11 ): 963 - 976 . https://doi.org/10.1631/jzus.B1600412 https://doi.org/10.1631/jzus.B1600412 .

Zhang JW , Barbieri D , Hoopen HT , et al. , 2015 . Microporous calcium phosphate ceramics driving osteogenesis through surface architecture . J Biomed Mater Res Part A , 103 ( 3 ): 1188 - 1199 . https://doi.org/10.1002/jbm.a.35272 https://doi.org/10.1002/jbm.a.35272

Zhang M , Matinlinna JP , Tsoi JKH , et al. , 2020 . Recent developments in biomaterials for long-bone segmental defect reconstruction: a narrative overview . J Orthop Translat , 22 : 26 - 33 . https://doi.org/10.1016/j.jot.2019.09.005 https://doi.org/10.1016/j.jot.2019.09.005

Zhang T , Wei QG , Zhou H , et al. , 2021 . Three-dimensional-printed individualized porous implants: a new “implant-bone” interface fusion concept for large bone defect treatment . Bioact Mater , 6 ( 11 ): 3659 - 3670 . https://doi.org/10.1016/j.bioactmat.2021.03.030 https://doi.org/10.1016/j.bioactmat.2021.03.030

Zhang WJ , Feng C , Yang GZ , et al. , 2017 . 3D-printed scaffolds with synergistic effect of hollow-pipe structure and bioactive ions for vascularized bone regeneration . Biomaterials , 135 : 85 - 95 . https://doi.org/10.1016/j.biomaterials.2017.05.005 https://doi.org/10.1016/j.biomaterials.2017.05.005

Zhao HY , Han YF , Pan C , et al. , 2021 . Design and mechanical properties verification of gradient Voronoi scaffold for bone tissue engineering . Micromachines (Basel) , 12 ( 6 ): 664 . https://doi.org/10.3390/mi12060664 https://doi.org/10.3390/mi12060664

Zhao Z , Li JC , Yao DR , et al. , 2022 . Mechanical and permeability properties of porous scaffolds developed by a Voronoi tessellation for bone tissue engineering . J Mater Chem B , 10 ( 46 ): 9699 - 9712 . https://doi.org/10.1039/d2tb01478e https://doi.org/10.1039/d2tb01478e

Zhong GY , Vaezi M , Mei XL , et al. , 2019 . Strategy for controlling the properties of bioactive poly-ether-ether-ketone/hydroxyapatite composites for bone tissue engineering scaffolds . ACS Omega , 4 ( 21 ): 19238 - 19245 . https://doi.org/10.1021/acsomega.9b02572 https://doi.org/10.1021/acsomega.9b02572

Zhu L , Liang HX , Lv F , et al. , 2021 . Design and compressive fatigue properties of irregular porous scaffolds for orthopedics fabricated using selective laser melting . ACS Biomater Sci Eng , 7 ( 4 ): 1663 - 1672 . https://doi.org/10.1021/acsbiomaterials.0c01392 https://doi.org/10.1021/acsbiomaterials.0c01392

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