Issue

Vol. 17 (2025)

Advances in the Development of Gradient Scaffolds Made of Nano-Micromaterials for Musculoskeletal Tissue Regeneration

https://doi.org/10.1007/s40820-024-01581-4
Lei Fang
Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China
Xiaoqi Lin
School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Sydney, NSW 2007, Australia
Ruian Xu
Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China
Lu Liu
School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Sydney, NSW 2007, Australia
Yu Zhang
Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China
Feng Tian
Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China
Jiao Jiao Li
School of Biomedical Engineering, Faculty of Engineering and IT, University of Technology Sydney, Sydney, NSW 2007, Australia
Jiajia Xue
Beijing Laboratory of Biomedical Materials, Beijing University of Chemical Technology, Beijing 100029, People’s Republic of China

Corresponding Author: Jiajia Xue

jiajiaxue@mail.buct.edu.cn

Nano-Micro Letters, Vol. 17 (2025), Article Number: 75

Abstract

The intricate hierarchical structure of musculoskeletal tissues, including bone and interface tissues, necessitates the use of complex scaffold designs and material structures to serve as tissue-engineered substitutes. This has led to growing interest in the development of gradient bone scaffolds with hierarchical structures mimicking the extracellular matrix of native tissues to achieve improved therapeutic outcomes. Building on the anatomical characteristics of bone and interfacial tissues, this review provides a summary of current strategies used to design and fabricate biomimetic gradient scaffolds for repairing musculoskeletal tissues, specifically focusing on methods used to construct compositional and structural gradients within the scaffolds. The latest applications of gradient scaffolds for the regeneration of bone, osteochondral, and tendon-to-bone interfaces are presented. Furthermore, the current progress of testing gradient scaffolds in physiologically relevant animal models of skeletal repair is discussed, as well as the challenges and prospects of moving these scaffolds into clinical application for treating musculoskeletal injuries.


Highlights:
1 This review highlights the gradient variations in the structural composition of musculoskeletal tissues and comprehensively examines recent progress in the fabrication and application of biomimetic gradient scaffolds for musculoskeletal repair.
2 The challenges and prospects of gradient scaffolds for clinical application are discussed.

Keywords

Gradient scaffolds Musculoskeletal tissues Advanced manufacturing Biomaterials Tissue regeneration
Fang, Lei, Xiaoqi Lin, Ruian Xu, Lu Liu, Yu Zhang, Feng Tian, Jiao Jiao Li, and Jiajia Xue. 2024. “Advances in the Development of Gradient Scaffolds Made of Nano-Micromaterials for Musculoskeletal Tissue Regeneration”. Nano-Micro Letters 17 (November):75. https://doi.org/10.1007/s40820-024-01581-4.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. X. Zhang, Q. Li, L. Li, J. Ouyang, T. Wang et al., Bioinspired mild photothermal effect-reinforced multifunctional fiber scaffolds promote bone regeneration. ACS Nano 17, 6466–6479 (2023). https://doi.org/10.1021/acsnano.2c11486
  2. H. Wei, J. Cui, K. Lin, J. Xie, X. Wang, Recent advances in smart stimuli-responsive biomaterials for bone therapeutics and regeneration. Bone Res. 10, 17 (2022). https://doi.org/10.1038/s41413-021-00180-y
  3. J. Fu, X. Wang, M. Yang, Y. Chen, J. Zhang et al., Scaffold-based tissue engineering strategies for osteochondral repair. Front. Bioeng. Biotechnol. 9, 812383 (2022). https://doi.org/10.3389/fbioe.2021.812383
  4. A. Ho-Shui-Ling, J. Bolander, L.E. Rustom, A.W. Johnson, F.P. Luyten et al., Bone regeneration strategies: Engineered scaffolds, bioactive molecules and stem cells current stage and future perspectives. Biomaterials 180, 143–162 (2018). https://doi.org/10.1016/j.biomaterials.2018.07.017
  5. T.M. Koushik, C.M. Miller, E. Antunes, Bone tissue engineering scaffolds: function of multi-material hierarchically structured scaffolds. Adv. Healthcare Mater. 12, 2202766 (2023). https://doi.org/10.1002/adhm.202202766
  6. G.L. Koons, M. Diba, A.G. Mikos, Materials design for bone-tissue engineering. Nat. Rev. Mater. 5, 584–603 (2020). https://doi.org/10.1038/s41578-020-0204-2
  7. A. Baawad, D. Jacho, T. Hamil, E. Yildirim-Ayan, D.-S. Kim, Polysaccharide-based composite scaffolds for osteochondral and enthesis regeneration. Tissue Eng. Part B Rev. 29, 123–140 (2023). https://doi.org/10.1089/ten.teb.2022.0114
  8. P. Chen, L. Li, L. Dong, S. Wang, Z. Huang et al., Gradient biomineralized silk fibroin nanofibrous scaffold with osteochondral inductivity for integration of tendon to bone. ACS Biomater. Sci. Eng. 7, 841–851 (2021). https://doi.org/10.1021/acsbiomaterials.9b01683
  9. S. Chen, A. McCarthy, J.V. John, Y. Su, J. Xie, Converting 2D nanofiber membranes to 3D hierarchical assemblies with structural and compositional gradients regulates cell behavior. Adv. Mater. 32, e2003754 (2020). https://doi.org/10.1002/adma.202003754
  10. R. Yang, Y. Zheng, Y. Zhang, G. Li, Y. Xu et al., Bipolar metal flexible electrospun fibrous membrane based on metal-organic framework for gradient healing of tendon-to-bone interface regeneration. Adv. Healthc. Mater. 11, e2200072 (2022). https://doi.org/10.1002/adhm.202200072
  11. S. Ansari, S. Khorshidi, A. Karkhaneh, Engineering of gradient osteochondral tissue: from nature to lab. Acta Biomater. 87, 41–54 (2019). https://doi.org/10.1016/j.actbio.2019.01.071
  12. B. Zhang, J. Huang, R.J. Narayan, Gradient scaffolds for osteochondral tissue engineering and regeneration. J. Mater. Chem. B 8, 8149–8170 (2020). https://doi.org/10.1039/d0tb00688b
  13. G. Xu, Y. Zhao, Y. Geng, S. Cao, P. Pan et al., Nano-hybrid gradient scaffold for articular repair. Colloids Surf. B Biointerfaces 208, 112116 (2021). https://doi.org/10.1016/j.colsurfb.2021.112116
  14. N. Yildirim, A. Amanzhanova, G. Kulzhanova, F. Mukasheva, C. Erisken, Osteochondral interface: regenerative engineering and challenges. ACS Biomater. Sci. Eng. 9, 1205–1223 (2023). https://doi.org/10.1021/acsbiomaterials.2c01321
  15. J. Lipner, H. Shen, L. Cavinatto, W. Liu, N. Havlioglu et al., In vivo evaluation of adipose-derived stromal cells delivered with a nanofiber scaffold for tendon-to-bone repair. Tissue Eng. Part A 21, 2766–2774 (2015). https://doi.org/10.1089/ten.TEA.2015.0101
  16. C. Li, L. Ouyang, J.P.K. Armstrong, M.M. Stevens, Advances in the fabrication of biomaterials for gradient tissue engineering. Trends Biotechnol. 39, 150–164 (2021). https://doi.org/10.1016/j.tibtech.2020.06.005
  17. R. Chen, J.S. Pye, J. Li, C.B. Little, J.J. Li, Multiphasic scaffolds for the repair of osteochondral defects: outcomes of preclinical studies. Bioact. Mater. 27, 505–545 (2023). https://doi.org/10.1016/j.bioactmat.2023.04.016
  18. L. Zhang, L. Fu, X. Zhang, L. Chen, Q. Cai et al., Hierarchical and heterogeneous hydrogel system as a promising strategy for diversified interfacial tissue regeneration. Biomater. Sci. 9, 1547–1573 (2021). https://doi.org/10.1039/d0bm01595d
  19. M. Altunbek, F. Afghah, O.S. Caliskan, J.J. Yoo, B. Koc, Design and bioprinting for tissue interfaces. Biofabrication 15, 022002 (2023). https://doi.org/10.1088/1758-5090/acb73d
  20. C. Gögele, J. Hahn, G. Schulze-Tanzil, Anatomical tissue engineering of the anterior cruciate ligament entheses. Int. J. Mol. Sci. 24, 9745 (2023). https://doi.org/10.3390/ijms24119745
  21. U.G.K. Wegst, H. Bai, E. Saiz, A.P. Tomsia, R.O. Ritchie, Bioinspired structural materials. Nat. Mater. 14, 23–36 (2015). https://doi.org/10.1038/nmat4089
  22. J.-M. Kim, C. Lin, Z. Stavre, M.B. Greenblatt, J.-H. Shim, Osteoblast-osteoclast communication and bone homeostasis. Cells 9, 2073 (2020). https://doi.org/10.3390/cells9092073
  23. W. Wang, K.W.K. Yeung, Bone grafts and biomaterials substitutes for bone defect repair: a review. Bioact. Mater. 2, 224–247 (2017). https://doi.org/10.1016/j.bioactmat.2017.05.007
  24. X. Bai, M. Gao, S. Syed, J. Zhuang, X. Xu et al., Bioactive hydrogels for bone regeneration. Bioact. Mater. 3, 401–417 (2018). https://doi.org/10.1016/j.bioactmat.2018.05.006
  25. G. Dang, W. Qin, Q. Wan, J. Gu, K. Wang et al., Regulation and reconstruction of cell phenotype gradients along the tendon-bone interface. Adv. Funct. Mater. 33, 2210275 (2023). https://doi.org/10.1002/adfm.202210275
  26. I. Sahafnejad-Mohammadi, S. Rahmati, N. Najmoddin, M. Bodaghi, Biomimetic polycaprolactone-graphene oxide composites for 3D printing bone scaffolds. Macromol. Mater. Eng. 308, 2200558 (2023). https://doi.org/10.1002/mame.202200558
  27. J. Scheinpflug, M. Pfeiffenberger, A. Damerau, F. Schwarz, M. Textor et al., Journey into bone models: a review. Genes 9, 247 (2018). https://doi.org/10.3390/genes9050247
  28. H. Qu, Z. Han, Z. Chen, L. Tang, C. Gao et al., Fractal design boosts extrusion-based 3D printing of bone-mimicking radial-gradient scaffolds. Research 2021, 9892689 (2021). https://doi.org/10.34133/2021/9892689
  29. H. Zhao, Y. Han, C. Pan, D. Yang, H. Wang et al., Design and mechanical properties verification of gradient voronoi scaffold for bone tissue engineering. Micromachines 12, 664 (2021). https://doi.org/10.3390/mi12060664
  30. M. Eryildiz, Fabrication of drug-loaded 3D-printed bone scaffolds with radial gradient porosity. J. Mater. Eng. Perform. 32, 4249–4257 (2023). https://doi.org/10.1007/s11665-022-07490-0
  31. H. Zhang, R. Wang, Y. Song, Y. Wang, Q. Hu, Research on dual-phase composite forming process and platform construction of radial gradient long bone scaffold. Bioengineering (Basel) 11, 869 (2024). https://doi.org/10.3390/bioengineering11090869
  32. L. Li, P. Wang, H. Liang, J. Jin, Y. Zhang et al., Design of a Haversian system-like gradient porous scaffold based on triply periodic minimal surfaces for promoting bone regeneration. J. Adv. Res. 54, 89–104 (2023). https://doi.org/10.1016/j.jare.2023.01.004
  33. S. Khorshidi, A. Karkhaneh, A review on gradient hydrogel/fiber scaffolds for osteochondral regeneration. J. Tissue Eng. Regen. Med. 12, e1974–e1990 (2018). https://doi.org/10.1002/term.2628
  34. P. Morouço, C. Fernandes, W. Lattanzi, Challenges and innovations in osteochondral regeneration: insights from biology and inputs from bioengineering toward the optimization of tissue engineering strategies. J. Funct. Biomater. 12, 17 (2021). https://doi.org/10.3390/jfb12010017
  35. M. Cucchiarini, H. Madry, Biomaterial-guided delivery of gene vectors for targeted articular cartilage repair. Nat. Rev. Rheumatol. 15, 18–29 (2019). https://doi.org/10.1038/s41584-018-0125-2
  36. W. Hu, Y. Chen, C. Dou, S. Dong, Microenvironment in subchondral bone: predominant regulator for the treatment of osteoarthritis. Ann. Rheum. Dis. 80, 413–422 (2021). https://doi.org/10.1136/annrheumdis-2020-218089
  37. S.R. Goldring, M.B. Goldring, Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage–bone crosstalk. Nat. Rev. Rheumatol. 12, 632–644 (2016). https://doi.org/10.1038/nrrheum.2016.148
  38. M. Zhu, W. Zhong, W. Cao, Q. Zhang, G. Wu et al., Chondroinductive/chondroconductive peptides and their-functionalized biomaterials for cartilage tissue engineering. Bioact. Mater. 9, 221–238 (2021). https://doi.org/10.1016/j.bioactmat.2021.07.004
  39. S. Muthu, J.V. Korpershoek, E.J. Novais, G.F. Tawy, A.P. Hollander et al., Failure of cartilage regeneration: emerging hypotheses and related therapeutic strategies. Nat. Rev. Rheumatol. 19, 403–416 (2023). https://doi.org/10.1038/s41584-023-00979-5
  40. M. Li, P. Song, W. Wang, Y. Xu, J. Li et al., Preparation and characterization of biomimetic gradient multi-layer cell-laden scaffolds for osteochondral integrated repair. J. Mater. Chem. B 10, 4172–4188 (2022). https://doi.org/10.1039/d2tb00576j
  41. A. Di Luca, C. Van Blitterswijk, L. Moroni, The osteochondral interface as a gradient tissue: from development to the fabrication of gradient scaffolds for regenerative medicine. Birth Defects Res. Part C Embryo Today Rev. 105, 34–52 (2015). https://doi.org/10.1002/bdrc.21092
  42. D. McGonagle, T.G. Baboolal, E. Jones, Native joint-resident mesenchymal stem cells for cartilage repair in osteoarthritis. Nat. Rev. Rheumatol. 13, 719–730 (2017). https://doi.org/10.1038/nrrheum.2017.182
  43. Z. Naghizadeh, A. Karkhaneh, A. Khojasteh, Self-crosslinking effect of chitosan and gelatin on alginate based hydrogels: injectable in situ forming scaffolds. Mater. Sci. Eng. C 89, 256–264 (2018). https://doi.org/10.1016/j.msec.2018.04.018
  44. X. Wang, Z. Zhu, H. Xiao, C. Luo, X. Luo et al., Three-dimensional, multiscale, and interconnected trabecular bone mimic porous tantalum scaffold for bone tissue engineering. ACS Omega 5, 22520–22528 (2020). https://doi.org/10.1021/acsomega.0c03127
  45. Y. Cao, P. Cheng, S. Sang, C. Xiang, Y. An et al., Mesenchymal stem cells loaded on 3D-printed gradient poly(ε-caprolactone)/methacrylated alginate composite scaffolds for cartilage tissue engineering. Regen. Biomater. 8, rbab019 (2021). https://doi.org/10.1093/rb/rbab019
  46. S. Zadegan, B. Vahidi, J. Nourmohammadi, A. Shojaee, N. Haghighipour, Evaluation of rabbit adipose derived stem cells fate in perfused multilayered silk fibroin composite scaffold for Osteochondral repair. J. Biomed. Mater. Res. Part B Appl. Biomater. 112, e35396 (2024). https://doi.org/10.1002/jbm.b.35396
  47. D. Clearfield, A. Nguyen, M. Wei, Biomimetic multidirectional scaffolds for zonal osteochondral tissue engineering via a lyophilization bonding approach. J. Biomed. Mater. Res. A 106, 948–958 (2018). https://doi.org/10.1002/jbm.a.36288
  48. A. Golebiowska, S.P. Nukavarapu, Bio-inspired zonal-structured matrices for bone-cartilage interface engineering. Biofabrication Biofabrication 14, 025016 (2022). https://doi.org/10.1088/1758-5090/ac52e1
  49. A. Vinhas, A.F. Almeida, M.T. Rodrigues, M.E. Gomes, Prospects of magnetically based approaches addressing inflammation in tendon tissues. Adv. Drug Deliv. Rev. 196, 114815 (2023). https://doi.org/10.1016/j.addr.2023.114815
  50. C. Zhu, J. Qiu, S. Thomopoulos, Y. Xia, Augmenting, tendon-to-bone repair with functionally graded scaffolds. Adv. Healthc. Mater. 10, e2002269 (2021). https://doi.org/10.1002/adhm.202002269
  51. S. Zhang, W. Ju, X. Chen, Y. Zhao, L. Feng et al., Hierarchical ultrastructure: an overview of what is known about tendons and future perspective for tendon engineering. Bioact. Mater. 8, 124–139 (2021). https://doi.org/10.1016/j.bioactmat.2021.06.007
  52. C. Chen, Y. Chen, M. Li, H. Xiao, Q. Shi et al., Functional decellularized fibrocartilaginous matrix graft for rotator cuff enthesis regeneration: a novel technique to avoid in-vitro loading of cells. Biomaterials 250, 119996 (2020). https://doi.org/10.1016/j.biomaterials.2020.119996
  53. H. Li, T. Wu, J. Xue, Q. Ke, Y. Xia, Transforming nanofiber mats into hierarchical scaffolds with graded changes in porosity and/or nanofiber alignment. Macromol. Rapid Commun. 41, e1900579 (2020). https://doi.org/10.1002/marc.201900579
  54. N. Friese, M.B. Gierschner, P. Schadzek, Y. Roger, A. Hoffmann, Regeneration of damaged tendon-bone junctions (entheses)-TAK1 as a potential node factor. Int. J. Mol. Sci. 21, 5177 (2020). https://doi.org/10.3390/ijms21155177
  55. L. Davenport Huyer, B. Zhang, A. Korolj, M. Montgomery, S. Drecun et al., Highly elastic and moldable polyester biomaterial for cardiac tissue engineering applications. ACS Biomater. Sci. Eng. 2, 780–788 (2016). https://doi.org/10.1021/acsbiomaterials.5b00525
  56. P. Shang, Y. Xiang, J. Du, S. Chen, B. Cheng et al., Gradient bipolar nanofiber scaffolds with a structure of biomimetic tendon-bone interface as rotator cuff patches. ACS Appl. Polym. Mater. 5, 6107–6116 (2023). https://doi.org/10.1021/acsapm.3c00791
  57. X. Xie, J. Cai, Y. Yao, Y. Chen, A.U.R. Khan et al., A woven scaffold with continuous mineral gradients for tendon-to-bone tissue engineering. Compos. Part B Eng. 212, 108679 (2021). https://doi.org/10.1016/j.compositesb.2021.108679
  58. W. Ji, F. Han, X. Feng, L. Shi, H. Ma et al., Cocktail-like gradient gelatin/hyaluronic acid bioimplant for enhancing tendon-bone healing in fatty-infiltrated rotator cuff injury models. Int. J. Biol. Macromol. 244, 125421 (2023). https://doi.org/10.1016/j.ijbiomac.2023.125421
  59. C. Yu, R. Chen, J. Chen, T. Wang, Y. Wang et al., Enhancing tendon-bone integration and healing with advanced multi-layer nanofiber-reinforced 3D scaffolds for acellular tendon complexes. Mater. Today Bio 26, 101099 (2024). https://doi.org/10.1016/j.mtbio.2024.101099
  60. W. Wei, H. Dai, Articular cartilage and osteochondral tissue engineering techniques: recent advances and challenges. Bioact. Mater. 6, 4830–4855 (2021). https://doi.org/10.1016/j.bioactmat.2021.05.011
  61. M. Qasim, D.S. Chae, N.Y. Lee, Bioengineering strategies for bone and cartilage tissue regeneration using growth factors and stem cells. J. Biomed. Mater. Res. A 108, 394–411 (2020). https://doi.org/10.1002/jbm.a.36817
  62. S. Camarero-Espinosa, I. Beeren, H. Liu, D.B. Gomes, J. Zonderland et al., 3D niche-inspired scaffolds as a stem cell delivery system for the regeneration of the osteochondral interface. Adv. Mater. 36, e2310258 (2024). https://doi.org/10.1002/adma.202310258
  63. A.J. Boys, H. Zhou, J.B. Harrod, M.C. McCorry, L.A. Estroff et al., Top-down fabrication of spatially controlled mineral-gradient scaffolds for interfacial tissue engineering. ACS Biomater. Sci. Eng. 5, 2988–2997 (2019). https://doi.org/10.1021/acsbiomaterials.9b00176
  64. S.M. Bittner, B.T. Smith, L. Diaz-Gomez, C.D. Hudgins, A.J. Melchiorri et al., Fabrication and mechanical characterization of 3D printed vertical uniform and gradient scaffolds for bone and osteochondral tissue engineering. Acta Biomater. 90, 37–48 (2019). https://doi.org/10.1016/j.actbio.2019.03.041
  65. C. Wang, W. Huang, Y. Zhou, L. He, Z. He et al., 3D printing of bone tissue engineering scaffolds. Bioact. Mater. 5, 82–91 (2020). https://doi.org/10.1016/j.bioactmat.2020.01.004
  66. T.D. Ngo, A. Kashani, G. Imbalzano, K.T.Q. Nguyen, D. Hui, Additive manufacturing (3D printing): a review of materials, methods, applications and challenges. Compos. Part B Eng. 143, 172–196 (2018). https://doi.org/10.1016/j.compositesb.2018.02.012
  67. B. Liao, R.F. Xia, W. Li, D. Lu, Z.M. Jin, 3D-printed Ti6Al4V scaffolds with graded triply periodic minimal surface structure for bone tissue engineering. J. Mater. Eng. Perform. 30, 4993–5004 (2021). https://doi.org/10.1007/s11665-021-05580-z
  68. A. Bagheri, J. Jin, Photopolymerization in 3D printing. ACS Appl. Polym. Mater. 1, 593–611 (2019). https://doi.org/10.1021/acsapm.8b00165
  69. L. Li, R. Hao, J. Qin, J. Song, X. Chen et al., Electrospun fibers control drug delivery for tissue regeneration and cancer therapy. Adv. Fiber Mater. 4, 1375–1413 (2022). https://doi.org/10.1007/s42765-022-00198-9
  70. L. Wang, T. Zhu, Y. Kang, J. Zhang, J. Du et al., Crimped nanofiber scaffold mimicking tendon-to-bone interface for fatty-infiltrated massive rotator cuff repair. Bioact. Mater. 16, 149–161 (2022). https://doi.org/10.1016/j.bioactmat.2022.01.031
  71. Z. Chen, H. Xiao, H. Zhang, Q. Xin, H. Zhang et al., Heterogenous hydrogel mimicking the osteochondral ECM applied to tissue regeneration. J. Mater. Chem. B 9, 8646–8658 (2021). https://doi.org/10.1039/D1TB00518A
  72. H. Zhang, S. Wu, W. Chen, Y. Hu, Z. Geng et al., Bone/cartilage targeted hydrogel: strategies and applications. Bioact. Mater. 23, 156–169 (2022). https://doi.org/10.1016/j.bioactmat.2022.10.028
  73. L. Chen, L. Wei, X. Su, L. Qin, Z. Xu et al., Preparation and characterization of biomimetic functional scaffold with gradient structure for osteochondral defect repair. Bioengineering 10, 213 (2023). https://doi.org/10.3390/bioengineering10020213
  74. Z. Zhao, R. Li, H. Ruan, Z. Cai, Y. Zhuang et al., Biological signal integrated microfluidic hydrogel microspheres for promoting bone regeneration. Chem. Eng. J. 436, 135176 (2022). https://doi.org/10.1016/j.cej.2022.135176
  75. M.K. Kim, K. Paek, S.M. Woo, J.A. Kim, Bone-on-a-chip: biomimetic models based on microfluidic technologies for biomedical applications. ACS Biomater. Sci. Eng. 9, 3058–3073 (2023). https://doi.org/10.1021/acsbiomaterials.3c00066
  76. P. Pan, X. Chen, K. Metavarayuth, J. Su, Q. Wang, Self-assembled supramolecular systems for bone engineering applications. Curr. Opin. Colloid Interface Sci. 35, 104–111 (2018). https://doi.org/10.1016/j.cocis.2018.01.015
  77. X. Lin, Q. Wang, C. Gu, M. Li, K. Chen et al., Smart nanosacrificial layer on the bone surface prevents osteoporosis through acid-base neutralization regulated biocascade effects. J. Am. Chem. Soc. 142, 17543–17556 (2020). https://doi.org/10.1021/jacs.0c07309
  78. K. Maji, K. Pramanik, Electrospun scaffold for bone regeneration. Int. J. Polym. Mater. Polym. Biomater. 71, 842–857 (2022). https://doi.org/10.1080/00914037.2021.1915784
  79. Z. Wang, Y. Wang, J. Yan, K. Zhang, F. Lin et al., Pharmaceutical electrospinning and 3D printing scaffold design for bone regeneration. Adv. Drug Deliv. Rev. 174, 504–534 (2021). https://doi.org/10.1016/j.addr.2021.05.007
  80. J. Xue, T. Wu, Y. Xia, Perspective: Aligned arrays of electrospun nanofibers for directing cell migration. APL Mater. 6, 120902 (2018). https://doi.org/10.1063/1.5058083
  81. Z. Fan, H. Liu, Z. Ding, L. Xiao, Q. Lu et al., Simulation of cortical and cancellous bone to accelerate tissue regeneration. Adv. Funct. Mater. 33, 2301839 (2023). https://doi.org/10.1002/adfm.202301839
  82. W. Liu, J. Lipner, J. Xie, C.N. Manning, S. Thomopoulos et al., Nanofiber scaffolds with gradients in mineral content for spatial control of osteogenesis. ACS Appl. Mater. Interfaces 6, 2842–2849 (2014). https://doi.org/10.1021/am405418g
  83. W. Liu, Q. Sun, Z.-L. Zheng, Y.-T. Gao, G.-Y. Zhu et al., Topographic cues guiding cell polarization via distinct cellular mechanosensing pathways. Small 18, e2104328 (2022). https://doi.org/10.1002/smll.202104328
  84. S.K. Perikamana, J. Lee, T. Ahmad, Y. Jeong, D.G. Kim et al., Effects of immobilized BMP-2 and nanofiber morphology on in vitro osteogenic differentiation of hMSCs and in vivo collagen assembly of regenerated bone. ACS Appl. Mater. Interfaces 7, 8798–8808 (2015). https://doi.org/10.1021/acsami.5b01340
  85. Q. Chen, C. Wang, X. Zhang, G. Chen, Q. Hu et al., In situ sprayed bioresponsive immunotherapeutic gel for post-surgical cancer treatment. Nat. Nanotechnol. 14, 89–97 (2019). https://doi.org/10.1038/s41565-018-0319-4
  86. R.K. Tindell, L.P. Busselle, J.L. Holloway, Magnetic fields enable precise spatial control over electrospun fiber alignment for fabricating complex gradient materials. J. Biomed. Mater. Res. A 111, 778–789 (2023). https://doi.org/10.1002/jbm.a.37492
  87. M.L. Tanes, J. Xue, Y. Xia, A general strategy for generating gradients of bioactive proteins on electrospun nanofiber mats by masking with bovine serum albumin. J. Mater. Chem. B 5, 5580–5587 (2017). https://doi.org/10.1039/C7TB00974G
  88. T. Wu, J. Xue, H. Li, C. Zhu, X. Mo et al., General method for generating circular gradients of active proteins on nanofiber scaffolds sought for wound closure and related applications. ACS Appl. Mater. Interfaces 10, 8536–8545 (2018). https://doi.org/10.1021/acsami.8b00129
  89. Z. Qiao, M. Lian, Y. Han, B. Sun, X. Zhang et al., Bioinspired stratified electrowritten fiber-reinforced hydrogel constructs with layer-specific induction capacity for functional osteochondral regeneration. Biomaterials 266, 120385 (2021). https://doi.org/10.1016/j.biomaterials.2020.120385
  90. I. Calejo, R. Costa-Almeida, R.L. Reis, M.E. Gomes, A textile platform using continuous aligned and textured composite microfibers to engineer tendon-to-bone interface gradient scaffolds. Adv. Healthc. Mater. 8, e1900200 (2019). https://doi.org/10.1002/adhm.201900200
  91. G. Narayanan, L.S. Nair, C.T. Laurencin, Regenerative engineering of the rotator cuff of the shoulder. ACS Biomater. Sci. Eng. 4, 751–786 (2018). https://doi.org/10.1021/acsbiomaterials.7b00631
  92. J. Cai, J. Wang, K. Ye, D. Li, C. Ai et al., Dual-layer aligned-random nanofibrous scaffolds for improving gradient microstructure of tendon-to-bone healing in a rabbit extra-articular model. Int. J. Nanomedicine 13, 3481–3492 (2018). https://doi.org/10.2147/IJN.S165633
  93. X. Wang, K. Xu, L. Mu, X. Zhang, G. Huang et al., Mussel-derived bioadaptive artificial tendon facilitates the cell proliferation and tenogenesis to promote tendon functional reconstruction. Adv. Healthc. Mater. 12, e2203400 (2023). https://doi.org/10.1002/adhm.202203400
  94. C. Yu, T. Wang, H. Diao, N. Liu, Y. Zhang et al., Photothermal-triggered structural change of nanofiber scaffold integrating with graded mineralization to promote tendon–bone healing. Adv. Fiber Mater. 4, 908–922 (2022). https://doi.org/10.1007/s42765-022-00154-7
  95. I. Roppolo, M. Caprioli, C.F. Pirri, S. Magdassi, 3D printing of self-healing materials. Adv. Mater. 36, 2305537 (2024). https://doi.org/10.1002/adma.202305537
  96. M.K. Joshi, H.R. Pant, A.P. Tiwari, H.J. Kim, C.H. Park et al., Multi-layered macroporous three-dimensional nanofibrous scaffold via a novel gas foaming technique. Chem. Eng. J. 275, 79–88 (2015). https://doi.org/10.1016/j.cej.2015.03.121
  97. L. Wang, Y. Qiu, Y. Guo, Y. Si, L. Liu et al., Smart, elastic, and nanofiber-based 3D scaffolds with self-deploying capability for osteoporotic bone regeneration. Nano Lett. 19, 9112–9120 (2019). https://doi.org/10.1021/acs.nanolett.9b04313
  98. G. Turnbull, J. Clarke, F. Picard, P. Riches, L. Jia et al., 3D bioactive composite scaffolds for bone tissue engineering. Bioact. Mater. 3, 278–314 (2018). https://doi.org/10.1016/j.bioactmat.2017.10.001
  99. L. Wu, X. Pei, B. Zhang, Z. Su, X. Gui et al., 3D-printed HAp bone regeneration scaffolds enable nano-scale manipulation of cellular mechanotransduction signals. Chem. Eng. J. 455, 140699 (2023). https://doi.org/10.1016/j.cej.2022.140699
  100. K. Garg, N.A. Pullen, C.A. Oskeritzian, J.J. Ryan, G.L. Bowlin, Macrophage functional polarization (M1/M2) in response to varying fiber and pore dimensions of electrospun scaffolds. Biomaterials 34, 4439–4451 (2013). https://doi.org/10.1016/j.biomaterials.2013.02.065
  101. S. Jiang, C. Lyu, P. Zhao, W. Li, W. Kong et al., Cryoprotectant enables structural control of porous scaffolds for exploration of cellular mechano-responsiveness in 3D. Nat. Commun. 10, 3491 (2019). https://doi.org/10.1038/s41467-019-11397-1
  102. M. Lafuente-Merchan, S. Ruiz-Alonso, F. García-Villén, I. Gallego, P. Gálvez-Martín et al., Progress in 3D bioprinting technology for osteochondral regeneration. Pharmaceutics 14, 1578 (2022). https://doi.org/10.3390/pharmaceutics14081578
  103. J. Zhang, D. Tong, H. Song, R. Ruan, Y. Sun et al., Osteoimmunity-regulating biomimetically hierarchical scaffold for augmented bone regeneration. Adv. Mater. 34, e2202044 (2022). https://doi.org/10.1002/adma.202202044
  104. J. Zhang, W. Hu, C. Ding, G. Yao, H. Zhao et al., Deferoxamine inhibits iron-uptake stimulated osteoclast differentiation by suppressing electron transport chain and MAPKs signaling. Toxicol. Lett. 313, 50–59 (2019). https://doi.org/10.1016/j.toxlet.2019.06.007
  105. C. Li, W. Zhang, Y. Nie, D. Jiang, J. Jia et al., Integrated and bifunctional bilayer 3D printing scaffold for osteochondral defect repair. Adv. Funct. Mater. 33, 2214158 (2023). https://doi.org/10.1002/adfm.202214158
  106. Y. Liu, L. Peng, L. Li, C. Huang, K. Shi et al., 3D-bioprinted BMSC-laden biomimetic Multiphasic scaffolds for efficient repair of osteochondral defects in an osteoarthritic rat model. Biomaterials 279, 121216 (2021). https://doi.org/10.1016/j.biomaterials.2021.121216
  107. X. Zhang, W. Song, K. Han, Z. Fang, E. Cho et al., Three-dimensional bioprinting of a structure-, composition-, and mechanics-graded biomimetic scaffold coated with specific decellularized extracellular matrix to improve the tendon-to-bone healing. ACS Appl. Mater. Interfaces 15, 28964–28980 (2023). https://doi.org/10.1021/acsami.3c03793
  108. R. Sinha, M. Cámara-Torres, P. Scopece, E. Verga Falzacappa, A. Patelli et al., A hybrid additive manufacturing platform to create bulk and surface composition gradients on scaffolds for tissue regeneration. Nat. Commun. 12, 500 (2021). https://doi.org/10.1038/s41467-020-20865-y
  109. I.A.O. Beeren, P.J. Dijkstra, A.F.H. Lourenço, R. Sinha, D.B. Gomes et al., Installation of click-type functional groups enable the creation of an additive manufactured construct for the osteochondral interface. Biofabrication (2022). https://doi.org/10.1088/1758-5090/aca3d4
  110. Y. Cai, S.Y. Chang, S.W. Gan, S. Ma, W.F. Lu et al., Nanocomposite bioinks for 3D bioprinting. Acta Biomater. 151, 45–69 (2022). https://doi.org/10.1016/j.actbio.2022.08.014
  111. S. Pouraghaei Sevari, J.K. Kim, C. Chen, A. Nasajpour, C.Y. Wang et al., Whitlockite-enabled hydrogel for craniofacial bone regeneration. ACS Appl. Mater. Interfaces 13, 35342–35355 (2021). https://doi.org/10.1021/acsami.1c07453
  112. A. Mokhtarzade, R. Imani, P. Shokrollahi, A gradient four-layered gelatin methacrylate/agarose construct as an injectable scaffold for mimicking osteochondral tissue. J. Mater. Sci. 58, 5735–5755 (2023). https://doi.org/10.1007/s10853-023-08374-x
  113. X. Hao, S. Miao, Z. Li, T. Wang, B. Xue et al., 3D printed structured porous hydrogel promotes osteogenic differentiation of BMSCs. Mater. Des. 227, 111729 (2023). https://doi.org/10.1016/j.matdes.2023.111729
  114. W. Wei, W. Liu, H. Kang, X. Zhang, R. Yu et al., A one-stone-two-birds strategy for osteochondral regeneration based on a 3D printable biomimetic scaffold with kartogenin biochemical stimuli gradient. Adv. Healthc. Mater. 12, 2300108 (2023). https://doi.org/10.1002/adhm.202300108
  115. D. Gan, Z. Wang, C. Xie, X. Wang, W. Xing et al., Mussel-inspired tough hydrogel with in situ nanohydroxyapatite mineralization for osteochondral defect repair. Adv. Healthc. Mater. 8, e1901103 (2019). https://doi.org/10.1002/adhm.201901103
  116. C. Parisi, L. Salvatore, L. Veschini, M.P. Serra, C. Hobbs et al., Biomimetic gradient scaffold of collagen-hydroxyapatite for osteochondral regeneration. J. Tissue Eng. 11, 2041731419896068 (2020). https://doi.org/10.1177/2041731419896068
  117. P. Mou, H. Peng, L. Zhou, L. Li, H. Li et al., A novel composite scaffold of Cu-doped nano calcium-deficient hydroxyapatite/multi-(amino acid) copolymer for bone tissue regeneration. Int. J. Nanomedicine 14, 3331–3343 (2019). https://doi.org/10.2147/IJN.S195316
  118. S. Stein, L. Kruck, D. Warnecke, A. Seitz et al., Osseointegration of titanium implants with a novel silver coating under dynamic loading. Eur. Cells Mater. 39, 249–259 (2020). https://doi.org/10.22203/ecm.v039a16
  119. C. Gao, W. Dai, X. Wang, L. Zhang, Y. Wang et al., Magnesium gradient-based hierarchical scaffold for dual-lineage regeneration of osteochondral defect. Adv. Funct. Mater. 33, 2304829 (2023). https://doi.org/10.1002/adfm.202304829
  120. R. Yang, G. Li, C. Zhuang, P. Yu, T. Ye et al., Gradient bimetallic ion-based hydrogels for tissue microstructure reconstruction of tendon-to-bone insertion. Sci. Adv. 7, eabg3816 (2021). https://doi.org/10.1126/sciadv.abg3816
  121. C. Li, L. Ouyang, I.J. Pence, A.C. Moore, Y. Lin et al., Buoyancy-driven gradients for biomaterial fabrication and tissue engineering. Adv. Mater. 31, e1900291 (2019). https://doi.org/10.1002/adma.201900291
  122. C. Li, J.P. Armstrong, I.J. Pence, W. Kit-Anan, J.L. Puetzer et al., Glycosylated superparamagnetic nanop gradients for osteochondral tissue engineering. Biomaterials 176, 24–33 (2018). https://doi.org/10.1016/j.biomaterials.2018.05.029
  123. L. Xiao, M. Wu, F. Yan, Y. Xie, Z. Liu et al., A radial 3D polycaprolactone nanofiber scaffold modified by biomineralization and silk fibroin coating promote bone regeneration in vivo. Int. J. Biol. Macromol. 172, 19–29 (2021). https://doi.org/10.1016/j.ijbiomac.2021.01.036
  124. S. Chen, H. Wang, V.L. Mainardi, G. Talò, A. McCarthy et al., Biomaterials with structural hierarchy and controlled 3D nanotopography guide endogenous bone regeneration. Sci. Adv. 7, eabg3089 (2021). https://doi.org/10.1126/sciadv.abg3089
  125. P. Kazimierczak, A. Benko, K. Palka, C. Canal, D. Kolodynska et al., Novel synthesis method combining a foaming agent with freeze-drying to obtain hybrid highly macroporous bone scaffolds. J. Mater. Sci. Technol. 43, 52–63 (2020). https://doi.org/10.1016/j.jmst.2020.01.006
  126. Z. Zhao, G. Li, H. Ruan, K. Chen, Z. Cai et al., Capturing magnesium ions via microfluidic hydrogel microspheres for promoting cancellous bone regeneration. ACS Nano 15, 13041–13054 (2021). https://doi.org/10.1021/acsnano.1c02147
  127. J.J. Paredes, N. Andarawis-Puri, Therapeutics for tendon regeneration: a multidisciplinary review of tendon research for improved healing. Ann. N. Y. Acad. Sci. 1383, 125–138 (2016). https://doi.org/10.1111/nyas.13228
  128. C. Zhu, S. Pongkitwitoon, J. Qiu, S. Thomopoulos, Y. Xia, Design and fabrication of a hierarchically structured scaffold for tendon-to-bone repair. Adv. Mater. 30, e1707306 (2018). https://doi.org/10.1002/adma.201707306
  129. W. Su, J. Guo, J. Xu, K. Huang, J. Chen et al., Gradient composite film with calcium phosphate silicate for improved tendon-to-Bone intergration. Chem. Eng. J. 404, 126473 (2021). https://doi.org/10.1016/j.cej.2020.126473
  130. H. Zhang, H. Huang, G. Hao, Y. Zhang, H. Ding et al., 3D printing hydrogel scaffolds with nanohydroxyapatite gradient to effectively repair osteochondral defects in rats. Adv. Funct. Mater. 31, 2006697 (2021). https://doi.org/10.1002/adfm.202006697
  131. Q. Wang, Y. Feng, M. He, W. Zhao, L. Qiu et al., A hierarchical Janus nanofibrous membrane combining direct osteogenesis and osteoimmunomodulatory functions for advanced bone regeneration. Adv. Funct. Mater. 31, 2008906 (2021). https://doi.org/10.1002/adfm.202008906
  132. C. Deng, J. Yang, H. He, Z. Ma, W. Wang et al., 3D bio-printed biphasic scaffolds with dual modification of silk fibroin for the integrated repair of osteochondral defects. Biomater. Sci. 9, 4891–4903 (2021). https://doi.org/10.1039/d1bm00535a
  133. D. Shi, J. Shen, Z. Zhang, C. Shi, M. Chen et al., Preparation and properties of dopamine-modified alginate/chitosan-hydroxyapatite scaffolds with gradient structure for bone tissue engineering. J. Biomed. Mater. Res. A 107, 1615–1627 (2019). https://doi.org/10.1002/jbm.a.36678
  134. Y. Wang, C. Ling, J. Chen, H. Liu, Q. Mo et al., 3D-printed composite scaffold with gradient structure and programmed biomolecule delivery to guide stem cell behavior for osteochondral regeneration. Biomater. Adv. 140, 213067 (2022). https://doi.org/10.1016/j.bioadv.2022.213067
  135. N. Zhang, Y. Wang, J. Zhang, J. Guo, J. He, Controlled domain gels with a biomimetic gradient environment for osteochondral tissue regeneration. Acta Biomater. 135, 304–317 (2021). https://doi.org/10.1016/j.actbio.2021.08.029
  136. A.-M. Wu, C. Bisignano, S. James, G.G. Abady, A. Abedi et al., 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 Longev. 2, e580–e592 (2021). https://doi.org/10.1016/S2666-7568(21)00172-0
  137. Y. Li, X. Wei, J. Zhou, L. Wei, The age-related changes in cartilage and osteoarthritis. Biomed. Res. Int. 2013, 916530 (2013). https://doi.org/10.1155/2013/916530
  138. H. Minagawa, N. Yamamoto, H. Abe, M. Fukuda, N. Seki et al., Prevalence of symptomatic and asymptomatic rotator cuff tears in the general population: from mass-screening in one village. J. Orthop. 10, 8–12 (2013). https://doi.org/10.1016/j.jor.2013.01.008
  139. L. Mancinelli, G. Intini, Age-associated declining of the regeneration potential of skeletal stem/progenitor cells. Front. Physiol. 14, 1087254 (2023). https://doi.org/10.3389/fphys.2023.1087254
  140. S. Ghouse, N. Reznikov, O.R. Boughton, S. Babu, K.C.G. Ng et al., The design and in vivo testing of a locally stiffness-matched porous scaffold. Appl. Mater. Today 15, 377–388 (2019). https://doi.org/10.1016/j.apmt.2019.02.017
  141. P. Diloksumpan, R.V. Bolaños, S. Cokelaere, B. Pouran, J. de Grauw et al., Orthotopic bone regeneration within 3D printed bioceramic scaffolds with region-dependent porosity gradients in an equine model. Adv. Healthc. Mater. 9, e1901807 (2020). https://doi.org/10.1002/adhm.201901807
  142. G. Li, L. Wang, W. Pan, F. Yang, W. Jiang et al., In vitro and in vivo study of additive manufactured porous Ti6Al4V scaffolds for repairing bone defects. Sci. Rep. 6, 34072 (2016). https://doi.org/10.1038/srep34072
  143. S. Jia, J. Wang, T. Zhang, W. Pan, Z. Li et al., Multilayered scaffold with a compact interfacial layer enhances osteochondral defect repair. ACS Appl. Mater. Interfaces 10, 20296–20305 (2018). https://doi.org/10.1021/acsami.8b03445
  144. Y. Zhang, D. Li, Y. Liu, L. Peng, D. Lu et al., 3D-bioprinted anisotropic bicellular living hydrogels boost osteochondral regeneration via reconstruction of cartilage-bone interface. Innovation 5, 100542 (2023). https://doi.org/10.1016/j.xinn.2023.100542
  145. Y.S. Zhang, G. Haghiashtiani, T. Hübscher, D.J. Kelly, J.M. Lee et al., 3D extrusion bioprinting. Nat. Rev. Methods Primers 1, 75 (2021). https://doi.org/10.1038/s43586-021-00073-8
  146. L. Wang, Z. Wang, Immune responses to silk proteins in vitro and in vivo: lessons learnt. Silk-based biomaterials for tissue engineering, regenerative and precision medicine (Elsevier, Amsterdam, 2024), pp.385–413. https://doi.org/10.1016/b978-0-323-96017-5.00006-6
  147. S. Tajvar, A. Hadjizadeh, S.S. Samandari, Scaffold degradation in bone tissue engineering: an overview. Int. Biodeterior. Biodegrad. 180, 105599 (2023). https://doi.org/10.1016/j.ibiod.2023.105599
  148. Q. Zhang, Y. Jiang, Y. Zhang, Z. Ye, W. Tan et al., Effect of porosity on long-term degradation of poly (ε-caprolactone) scaffolds and their cellular response. Polym. Degrad. Stab. 98, 209–218 (2013). https://doi.org/10.1016/j.polymdegradstab.2012.10.008
  149. J. Ye, N. Liu, Z. Li, L. Liu, M. Zheng et al., Injectable, hierarchically degraded bioactive scaffold for bone regeneration. ACS Appl. Mater. Interfaces 15, 11458–11473 (2023). https://doi.org/10.1021/acsami.2c18824
  150. J. Xue, T. Wu, J. Qiu, S. Rutledge, M.L. Tanes et al., Promoting cell migration and neurite extension along uniaxially aligned nanofibers with biomacromolecular ps in a density gradient. Adv. Funct. Mater. 30, 2002031 (2020). https://doi.org/10.1002/adfm.202002031
  151. X. Zhang, L. Li, J. Ouyang, L. Zhang, J. Xue et al., Electroactive electrospun nanofibers for tissue engineering. Nano Today 39, 101196 (2021). https://doi.org/10.1016/j.nantod.2021.101196
  152. C. Xie, J. Ye, R. Liang, X. Yao, X. Wu et al., Advanced strategies of biomimetic tissue-engineered grafts for bone regeneration. Adv. Healthc. Mater. 10, e2100408 (2021). https://doi.org/10.1002/adhm.202100408
  153. P. Zhang, Z. Teng, M. Zhou, X. Yu, H. Wen et al., Upconversion 3D bioprinting for noninvasive in vivo molding. Adv. Mater. 36, e2310617 (2024). https://doi.org/10.1002/adma.202310617
  154. P. Pei, H. Hu, Y. Chen, S. Wang, J. Chen et al., NIR-II ratiometric lanthanide-dye hybrid nanoprobes doped bioscaffolds for in situ bone repair monitoring. Nano Lett. 22, 783–791 (2022). https://doi.org/10.1021/acs.nanolett.1c04356
  155. L.B. Jiang, S.L. Ding, W. Ding, D.H. Su, F.X. Zhang et al., Injectable sericin based nanocomposite hydrogel for multi-modal imaging-guided immunomodulatory bone regeneration. Chem. Eng. J. 418, 129323 (2021). https://doi.org/10.1016/j.cej.2021.129323
  156. B. Li, M. Zhao, L. Feng, C. Dou, S. Ding et al., Organic NIR-II molecule with long blood half-life for in vivo dynamic vascular imaging. Nat. Commun. 11, 3102 (2020). https://doi.org/10.1038/s41467-020-16924-z
  157. P. Pei, Y. Chen, C. Sun, Y. Fan, Y. Yang et al., X-ray-activated persistent luminescence nanomaterials for NIR-II imaging. Nat. Nanotechnol. 16, 1011–1018 (2021). https://doi.org/10.1038/s41565-021-00922-3
  158. L. Zelaya-Lainez, H. Kariem, W. Nischkauer, A. Limbeck, C. Hellmich, “Variances” and “in-variances” in hierarchical porosity and composition, across femoral tissues from cow, horse, ostrich, emu, pig, rabbit, and frog. Mater. Sci. Eng. C 117, 111234 (2020). https://doi.org/10.1016/j.msec.2020.111234
  159. H. Zhang, L. Yang, X.G. Yang, F. Wang, J.T. Feng et al., Demineralized bone matrix carriers and their clinical applications: an overview. Orthop. Surg. 11, 725–737 (2019). https://doi.org/10.1111/os.12509
Read More
Author biographies are not available.
Download this PDF file
PDF
Statistic
Read Counter : 213 Download : 162

Most read articles by the same author(s)

<< < 1 2