Issue

Vol. 16 (2024)

Delivering Microrobots in the Musculoskeletal System

https://doi.org/10.1007/s40820-024-01464-8
Mumin Cao
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China
Renwang Sheng
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China
Yimin Sun
Jiangsu Key Laboratory for Design and Manufacture of Micro‑Nano Biomedical Instruments, School of Mechanical Engineering, Southeast University, Nanjing 210009, People’s Republic of China
Ying Cao
Jiangsu Key Laboratory for Design and Manufacture of Micro‑Nano Biomedical Instruments, School of Mechanical Engineering, Southeast University, Nanjing 210009, People’s Republic of China
Hao Wang
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China
Ming Zhang
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China
Yunmeng Pu
School of Medicine, Southeast University, Nanjing 210009, People’s Republic of China
Yucheng Gao
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China
Yuanwei Zhang
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China
Panpan Lu
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China
Gaojun Teng
Center of Interventional Radiology and Vascular Surgery, Department of Radiology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing 210009, People’s Republic of China
Qianqian Wang
Jiangsu Key Laboratory for Design and Manufacture of Micro‑Nano Biomedical Instruments, School of Mechanical Engineering, Southeast University, Nanjing 210009, People’s Republic of China
Yunfeng Rui
Department of Orthopaedics, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, Jiangsu, People’s Republic of China

Corresponding Author: Yunfeng Rui

ruiyunfeng@126.com

Nano-Micro Letters, Vol. 16 (2024), Article Number: 251

Abstract

Disorders of the musculoskeletal system are the major contributors to the global burden of disease and current treatments show limited efficacy. Patients often suffer chronic pain and might eventually have to undergo end-stage surgery. Therefore, future treatments should focus on early detection and intervention of regional lesions. Microrobots have been gradually used in organisms due to their advantages of intelligent, precise and minimally invasive targeted delivery. Through the combination of control and imaging systems, microrobots with good biosafety can be delivered to the desired area for treatment. In the musculoskeletal system, microrobots are mainly utilized to transport stem cells/drugs or to remove hazardous substances from the body. Compared to traditional biomaterial and tissue engineering strategies, active motion improves the efficiency and penetration of local targeting of cells/drugs. This review discusses the frontier applications of microrobotic systems in different tissues of the musculoskeletal system. We summarize the challenges and barriers that hinder clinical translation by evaluating the characteristics of different microrobots and finally point out the future direction of microrobots in the musculoskeletal system.


Highlights:
1 A systematic review of recent advances of microrobots applied in the musculoskeletal system with an emphasis on design strategies of microrobotic systems for tissue regeneration.
2 The fabrication, motion and control, and image-guided delivery of microrobots in the musculoskeletal system are reviewed based on the up-to-date works.
3 Prospects and challenges for future clinical translation of microrobots in the musculoskeletal system and regenerative medicine are discussed.

Keywords

Microrobot Musculoskeletal system Targeted delivery Microrobotic systems Magnetic actuation
Cao, Mumin, Renwang Sheng, Yimin Sun, Ying Cao, Hao Wang, Ming Zhang, Yunmeng Pu, Yucheng Gao, Yuanwei Zhang, Panpan Lu, Gaojun Teng, Qianqian Wang, and Yunfeng Rui. 2024. “Delivering Microrobots in the Musculoskeletal System”. Nano-Micro Letters 16 (July):251. https://doi.org/10.1007/s40820-024-01464-8.
Download Citation
Endnote/Zotero/Mendeley (RIS)
BibTeX
References
  1. C. Abbafati, K.M. Abbas, M. Abbasi, M. Abbasifard, M. Abbasi-Kangevari et al., Collaborators global burden of 369 diseases and injuries in 204 countries and territories, 1990–2019: a systematic analysis for the global burden of disease study 2019. Lancet 396, 1204–1222 (2020). https://doi.org/10.1016/S0140-6736(20)30925-9
  2. R. Gheno, J.M. Cepparo, C.E. Rosca, A. Cotten, Musculoskeletal disorders in the elderly. J. Clin. Imag. Sci. 2, 39 (2012). https://doi.org/10.4103/2156-7514.99151
  3. R. Buchbinder, C. Maher, I.A. Harris, Setting the research agenda for improving health care in musculoskeletal disorders. Nat. Rev. Rheumatol. 11, 597–605 (2015). https://doi.org/10.1038/nrrheum.2015.81
  4. A. Cieza, K. Causey, K. Kamenov, S.W. Hanson, S. Chatterji et al., Global estimates of the need for rehabilitation based on the global burden of disease study 2019: a systematic analysis for the global burden of disease study 2019. Lancet 396, 2006–2017 (2021). https://doi.org/10.1016/S0140-6736(20)32340-0
  5. S. Chatterji, J. Byles, D. Cutler, T. Seeman, E. Verdes, Health, functioning, and disability in older adults: present status and future implications. Lancet 385, 563–575 (2015). https://doi.org/10.1016/S0140-6736(14)61462-8
  6. J.E. Morley, Pharmacologic options for the treatment of sarcopenia. Calcif. Tissue Int. 98, 319–333 (2016). https://doi.org/10.1007/s00223-015-0022-5
  7. K.N. Tu, J.D. Lie, C.K.V. Wan, M. Cameron, A.G. Austel et al., Osteoporosis: a review of treatment options. P&T 43, 92–104 (2018)
  8. W. Zhang, H. Ouyang, C.R. Dass, J. Xu, Current research on pharmacologic and regenerative therapies for osteoarthritis. Bone Res. 4, 15040 (2016). https://doi.org/10.1038/boneres.2015.40
  9. J. Huang, Y. Chen, C. Tang, Y. Fei, H. Wu et al., The relationship between substrate topography and stem cell differentiation in the musculoskeletal system. Cell. Mol. Life Sci. 76, 505–521 (2019). https://doi.org/10.1007/s00018-018-2945-2
  10. M. Stephenson, W. Grayson, Recent advances in bioreactors for cell-based therapies. [version 1; peer review: 2 approved]. F1000Research 7 (F1000 Faculty Rev):517 (2018). https://doi.org/10.12688/f1000research.12533.1
  11. J.M. Anderson, A. Rodriguez, D.T. Chang, Foreign body reaction to biomaterials. Semin. Immunol. 20, 86–100 (2008). https://doi.org/10.1016/j.smim.2007.11.004
  12. J. Ye, C. Xie, C. Wang, J. Huang, Z. Yin et al., Promoting musculoskeletal system soft tissue regeneration by biomaterial-mediated modulation of macrophage polarization. Bioact. Mater. 6, 4096–4109 (2021). https://doi.org/10.1016/j.bioactmat.2021.04.017
  13. C. Murphy, J. Withrow, M. Hunter, Y. Liu, Y.L. Tang et al., Emerging role of extracellular vesicles in musculoskeletal diseases. Mol. Aspects Med. 60, 123–128 (2018). https://doi.org/10.1016/j.mam.2017.09.006
  14. X. Yao, W. Wei, X. Wang, C. Li, M. Björklund et al., Stem cell derived exosomes: microRNA therapy for age-related musculoskeletal disorders. Biomaterials 224, 119492 (2019). https://doi.org/10.1016/j.biomaterials.2019.119492
  15. C.H. Evans, J. Huard, Gene therapy approaches to regenerating the musculoskeletal system. Nat. Rev. Rheumatol. 11, 234–242 (2015). https://doi.org/10.1038/nrrheum.2015.28
  16. C.H. Evans, P.D. Robbins, Genetically augmented tissue engineering of the musculoskeletal system. Clin. Orthop. Relat. Res. (1999). https://doi.org/10.1097/00003086-199910001-00040
  17. C. Evans, Using genes to facilitate the endogenous repair and regeneration of orthopaedic tissues. Int. Orthop. 38, 1761–1769 (2014). https://doi.org/10.1007/s00264-014-2423-x
  18. 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
  19. E. Basad, B. Ishaque, G. Bachmann, H. Stürz, J. Steinmeyer, Matrix-induced autologous chondrocyte implantation versus microfracture in the treatment of cartilage defects of the knee: a 2-year randomised study. Knee Surg. Sports Traumatol. Arthrosc. 18, 519–527 (2010). https://doi.org/10.1007/s00167-009-1028-1
  20. B.J. Huang, J.C. Hu, K.A. Athanasiou, Cell-based tissue engineering strategies used in the clinical repair of articular cartilage. Biomaterials 98, 1–22 (2016). https://doi.org/10.1016/j.biomaterials.2016.04.018
  21. D.C. Carneiro, L.T. Araújo, G.C. Santos, P.K.F. Damasceno, J.L. Vieira et al., Clinical trials with mesenchymal stem cell therapies for osteoarthritis: challenges in the regeneration of articular cartilage. Int. J. Mol. Sci. 24, 9939 (2023). https://doi.org/10.3390/ijms24129939
  22. K. Čamernik, A. Barlič, M. Drobnič, J. Marc, M. Jeras et al., Mesenchymal stem cells in the musculoskeletal system: from animal models to human tissue regeneration? Stem Cell Rev. Rep. 14, 346–369 (2018). https://doi.org/10.1007/s12015-018-9800-6
  23. H.I.M.F.L. Pas, M.H. Moen, H.J. Haisma, M. Winters, No evidence for the use of stem cell therapy for tendon disorders: a systematic review. Br. J. Sports Med. 51, 996–1002 (2017). https://doi.org/10.1136/bjsports-2016-096794
  24. B.J. Nelson, S. Pané, Delivering drugs with microrobots biomedical microrobots could overcome current challenges in targeted therapies. Science 382, 1120–1122 (2023). https://doi.org/10.1126/science.adh3073
  25. M. Wan, H. Chen, Q. Wang, Q. Niu, P. Xu et al., Bio-inspired nitric-oxide-driven nanomotor. Nat. Commun. 10, 966 (2019). https://doi.org/10.1038/s41467-019-08670-8
  26. X. Ma, X. Wang, K. Hahn, S. Sánchez, Motion control of urea-powered biocompatible hollow microcapsules. ACS Nano 10, 3597–3605 (2016). https://doi.org/10.1021/acsnano.5b08067
  27. S. Gao, J. Hou, J. Zeng, J.J. Richardson, Z. Gu et al., Superassembled biocatalytic porous framework micromotors with reversible and sensitive pH-speed regulation at ultralow physiological H2O2 concentration. Adv. Funct. Mater. 29, 1808900 (2019). https://doi.org/10.1002/adfm.201808900
  28. A.C. Hortelão, R. Carrascosa, N. Murillo-Cremaes, T. Patiño, S. Sánchez, Targeting 3D bladder cancer spheroids with urease-powered nanomotors. ACS Nano 13, 429–439 (2019). https://doi.org/10.1021/acsnano.8b06610
  29. M. Hansen-Bruhn, B.E. de Ávila, M. Beltrán-Gastélum, J. Zhao, D.E. Ramírez-Herrera et al., Active intracellular delivery of a Cas9/sgRNA complex using ultrasound-propelled nanomotors. Angew. Chem. Int. Ed. 57, 2657–2661 (2018). https://doi.org/10.1002/anie.201713082
  30. Y. Shen, W. Zhang, G. Li, P. Ning, Z. Li et al., Adaptive control of nanomotor swarms for magnetic-field-programmed cancer cell destruction. ACS Nano 15, 20020–20031 (2021). https://doi.org/10.1021/acsnano.1c07615
  31. R. Dong, Q. Zhang, W. Gao, A. Pei, B. Ren, Highly efficient light-driven TiO2-Au Janus micromotors. ACS Nano 10, 839–844 (2016). https://doi.org/10.1021/acsnano.5b05940
  32. M. Ussia, M. Urso, S. Kment, T. Fialova, K. Klima et al., Light-propelled nanorobots for facial titanium implants biofilms removal. Small 18, e2200708 (2022). https://doi.org/10.1002/smll.202200708
  33. Z. Cong, S. Tang, L. Xie, M. Yang, Y. Li et al., Magnetic-powered Janus cell robots loaded with oncolytic adenovirus for active and targeted virotherapy of bladder cancer. Adv. Mater. 34, e2201042 (2022). https://doi.org/10.1002/adma.202201042
  34. S. Ahmed, D.T. Gentekos, C.A. Fink, T.E. Mallouk, Self-assembly of nanorod motors into geometrically regular multimers and their propulsion by ultrasound. ACS Nano 8, 11053–11060 (2014). https://doi.org/10.1021/nn5039614
  35. X. Yi, H. Zhou, Y. Chao, S. Xiong, J. Zhong et al., Bacteria-triggered tumor-specific thrombosis to enable potent photothermal immunotherapy of cancer. Sci. Adv. 6, eaba3546 (2020). https://doi.org/10.1126/sciadv.aba3546
  36. D. Blackiston, E. Lederer, S. Kriegman, S. Garnier, J. Bongard et al., A cellular platform for the development of synthetic living machines. Sci. Robot. 6, eabf1571 (2021). https://doi.org/10.1126/scirobotics.abf1571
  37. O. Felfoul, M. Mohammadi, S. Taherkhani, D. de Lanauze, Y. Zhong Xu et al., Magneto-aerotactic bacteria deliver drug-containing nanoliposomes to tumour hypoxic regions. Nat. Nanotechnol. 11, 941–947 (2016). https://doi.org/10.1038/nnano.2016.137
  38. H. Xu, M. Medina-Sánchez, V. Magdanz, L. Schwarz, F. Hebenstreit et al., Sperm-hybrid micromotor for targeted drug delivery. ACS Nano 12, 327–337 (2018). https://doi.org/10.1021/acsnano.7b06398
  39. B.J. Nelson, I.K. Kaliakatsos, J.J. Abbott, Microrobots for minimally invasive medicine. Annu. Rev. Biomed. Eng. 12, 55–85 (2010). https://doi.org/10.1146/annurev-bioeng-010510-103409
  40. H. Mu, C. Liu, Q. Zhang, H. Meng, S. Yu et al., Magnetic-driven hydrogel microrobots selectively enhance synthetic lethality in MTAP-deleted osteosarcoma. Front. Bioeng. Biotechnol. 10, 911455 (2022). https://doi.org/10.3389/fbioe.2022.911455
  41. C. Xu, Y. Jiang, H. Wang, Y. Zhang, Y. Ye et al., Arthritic microenvironment actuated nanomotors for active rheumatoid arthritis therapy. Adv. Sci. 10, e2204881 (2023). https://doi.org/10.1002/advs.202204881
  42. G.-Z. Yang, J. Bellingham, P.E. Dupont, P. Fischer, L. Floridi et al., The grand challenges of Science Robotics. Sci. Robot. 3, eaar7650 (2018). https://doi.org/10.1126/scirobotics.aar7650
  43. Y. Alapan, O. Yasa, B. Yigit, I.C. Yasa, P. Erkoc et al., Microrobotics and microorganisms: biohybrid autonomous cellular robots. Annu. Rev. Control Robot. Auton. Syst. 2, 205–230 (2019). https://doi.org/10.1146/annurev-control-053018-023803
  44. Q. Wang, L. Zhang, External power-driven microrobotic swarm: from fundamental understanding to imaging-guided delivery. ACS Nano 15, 149–174 (2021). https://doi.org/10.1021/acsnano.0c07753
  45. Q. Wang, J. Zhang, J. Yu, J. Lang, Z. Lyu et al., Untethered small-scale machines for microrobotic manipulation: from individual and multiple to collective machines. ACS Nano 17, 13081–13109 (2023). https://doi.org/10.1021/acsnano.3c05328
  46. F. Soto, E. Karshalev, F. Zhang, B. Esteban Fernandez de Avila, A. Nourhani et al., Smart materials for microrobots. Chem. Rev. 122, 5365–5403 (2022). https://doi.org/10.1021/acs.chemrev.0c00999
  47. F. Sylos-Labini, M. Zago, P.A. Guertin, F. Lacquaniti, Y.P. Ivanenko, Muscle coordination and locomotion in humans. Curr. Pharm. Des. 23, 1821–1833 (2017). https://doi.org/10.2174/1381612823666170125160820
  48. A. Oryan, S. Sahvieh, Effectiveness of chitosan scaffold in skin, bone and cartilage healing. Int. J. Biol. Macromol. 104, 1003–1011 (2017). https://doi.org/10.1016/j.ijbiomac.2017.06.124
  49. S. Roberts, P. Colombier, A. Sowman, C. Mennan, J.H.D. Rölfing et al., Ageing in the musculoskeletal system. Acta Orthop. 87, 15–25 (2016). https://doi.org/10.1080/17453674.2016.1244750
  50. D. Goltzman, The aging skeleton, in Advances in experimental medicine and biology. ed. by J.S. Rhim, A. Dritschilo, R. Kremer (Springer International Publishing, Cham, 2019), pp.153–160. https://doi.org/10.1007/978-3-030-22254-3_12
  51. R. Sheng, M. Cao, M. Song, M. Wang, Y. Zhang et al., Muscle-bone crosstalk via endocrine signals and potential targets for osteosarcopenia-related fracture. J. Orthop. Translat. 43, 36–46 (2023). https://doi.org/10.1016/j.jot.2023.09.007
  52. B. Kirk, J. Feehan, G. Lombardi, G. Duque, Muscle, bone, and fat crosstalk: the biological role of myokines, osteokines, and adipokines. Curr. Osteoporos. Rep. 18, 388–400 (2020). https://doi.org/10.1007/s11914-020-00599-y
  53. GBD 2016 Disease and injury incidence and prevalence collaborators, global, regional, and national incidence, prevalence, and years lived with disability for 328 diseases and injuries for 195 countries, 1990–2016: a systematic analysis for the global burden of disease study 2016. Lancet 390, pp. 1211–1259 (2017). https://doi.org/10.1016/S0140-6736(17)32154-2
  54. D.J. Hunter, S. Bierma-Zeinstra, Osteoarthritis. Lancet 393, 1745–1759 (2019). https://doi.org/10.1016/S0140-6736(19)30417-9
  55. M. Ondrésik, F.R. Azevedo Maia, A. da Silva Morais, A.C. Gertrudes, A.H. Dias Bacelar et al., Management of knee osteoarthritis. Current status and future trends. Biotechnol. Bioeng. 114, 717–739 (2017). https://doi.org/10.1002/bit.26182
  56. H. Madry, Surgical therapy in osteoarthritis. Osteoarthr. Cartil. 30, 1019–1034 (2022). https://doi.org/10.1016/j.joca.2022.01.012
  57. B.R. Freedman, D.J. Mooney, E. Weber, Advances toward transformative therapies for tendon diseases. Sci. Transl. Med. 14, eabl814 (2022). https://doi.org/10.1126/scitranslmed.abl8814
  58. G. Nourissat, F. Berenbaum, D. Duprez, Tendon injury: from biology to tendon repair. Nat. Rev. Rheumatol. 11, 223–233 (2015). https://doi.org/10.1038/nrrheum.2015.26
  59. J.L. Cook, C. Purdam, Is compressive load a factor in the development of tendinopathy? Br. J. Phys. Med. 46, 163–168 (2012). https://doi.org/10.1136/bjsports-2011-090414
  60. F. Abat, H. Alfredson, M. Cucchiarini, H. Madry, A. Marmotti et al., Current trends in tendinopathy: consensus of the ESSKA basic science committee. Part II: treatment options. J. Exp. Orthop. 5, 38 (2018). https://doi.org/10.1186/s40634-018-0145-5
  61. F. Oliva, D. Barisani, A. Grasso, N. Maffulli, Gene expression analysis in calcific tendinopathy of the rotator cuff. Eur. Cell. Mater. 21, 548–557 (2011). https://doi.org/10.22203/ecm.v021a41
  62. G.-C. Dai, H. Wang, Z. Ming, P.-P. Lu, Y.-J. Li et al., Heterotopic mineralization (ossification or calcification) in aged musculoskeletal soft tissues: a new candidate marker for aging. Ageing Res. Rev. 95, 102215 (2024). https://doi.org/10.1016/j.arr.2024.102215
  63. T.S.O. Sleeswijk Visser, A.C. van der Vlist, R.F. van Oosterom, P. van Veldhoven, J.A.N. Verhaar et al., Impact of chronic Achilles tendinopathy on health-related quality of life, work performance, healthcare utilisation and costs. BMJ Open Sport Exerc. Med. 7, e001023 (2021). https://doi.org/10.1136/bmjsem-2020-001023
  64. A.C. Colvin, N. Egorova, A.K. Harrison, A. Moskowitz, E.L. Flatow, National trends in rotator cuff repair. J. Bone Jt. Surg. Am. 94, 227–233 (2012). https://doi.org/10.2106/jbjs.j.00739
  65. S.A. Rodeo, Biologic augmentation of rotator cuff tendon repair. J. Shoulder Elbow Surg. 16, S191–S197 (2007). https://doi.org/10.1016/j.jse.2007.03.012
  66. D. Goutallier, J.-M. Postel, P. Gleyze, P. Leguilloux, S. Van, Driessche Influence of cuff muscle fatty degeneration on anatomic and functional outcomes after simple suture of full-thickness tears. J. Shoulder Elb. Surg. 12, 550–554 (2003). https://doi.org/10.1016/S1058-2746(03)00211-8
  67. Z. Wang, L. Xiang, F. Lin, Y. Tang, L. Deng et al., A biomaterial-based hedging immune strategy for scarless tendon healing. Adv. Mater. 35, 2200789 (2023). https://doi.org/10.1002/adma.202200789
  68. G.A. Rodan, T.J. Martin, Therapeutic approaches to bone diseases. Science 289, 1508–1514 (2000). https://doi.org/10.1126/science.289.5484.1508
  69. W. Chen, H. Lv, S. Liu, B. Liu, Y. Zhu et al., National incidence of traumatic fractures in China: a retrospective survey of 512 187 individuals. Lancet Glob. Health 5, e807–e817 (2017). https://doi.org/10.1016/S2214-109X(17)30222-X
  70. 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
  71. Q. Wang, J. Yan, J. Yang, B. Li, Nanomaterials promise better bone repair. Mater. Today 19, 451–463 (2016). https://doi.org/10.1016/j.mattod.2015.12.003
  72. M.A.A. Mahdy, Skeletal muscle fibrosis: an overview. Cell Tissue Res. 375, 575–588 (2019). https://doi.org/10.1007/s00441-018-2955-2
  73. B.T. Corona, J.C. Rivera, J.G. Owens, J.C. Wenke, C.R. Rathbone, Volumetric muscle loss leads to permanent disability following extremity trauma. J. Rehabil. Res. Dev. 52, 785–792 (2015). https://doi.org/10.1682/jrrd.2014.07.0165
  74. F. Relaix, P.S. Zammit, Satellite cells are essential for skeletal muscle regeneration: the cell on the edge returns centre stage. Development 139, 2845–2856 (2012). https://doi.org/10.1242/dev.069088
  75. A. Aurora, J.L. Roe, B.T. Corona, T.J. Walters, An acellular biologic scaffold does not regenerate appreciable de novo muscle tissue in rat models of volumetric muscle loss injury. Biomaterials 67, 393–407 (2015). https://doi.org/10.1016/j.biomaterials.2015.07.040
  76. K. Garg, C.L. Ward, B.J. Hurtgen, J.M. Wilken, D.J. Stinner et al., Volumetric muscle loss: persistent functional deficits beyond frank loss of tissue. J. Orthop. Res. 33, 40–46 (2015). https://doi.org/10.1002/jor.22730
  77. J. Larouche, S.M. Greising, B.T. Corona, C.A. Aguilar, Robust inflammatory and fibrotic signaling following volumetric muscle loss: a barrier to muscle regeneration. Cell Death Dis. 9, 409 (2018). https://doi.org/10.1038/s41419-018-0455-7
  78. B.F. Grogan, J.R. Hsu, Volumetric muscle loss. Am. Acad. Orthop. Surg. 19, S35–S37 (2011). https://doi.org/10.5435/00124635-201102001-00007
  79. B.J. Hurtgen, C.L. Ward, C.M. Leopold Wager, K. Garg, S.M. Goldman et al., Autologous minced muscle grafts improve endogenous fracture healing and muscle strength after musculoskeletal trauma. Physiol. Rep. 5, e13362 (2017). https://doi.org/10.14814/phy2.13362
  80. M.T.A. Li, N.J. Willett, B.A. Uhrig, R.E. Guldberg, G.L. Warren, Functional analysis of limb recovery following autograft treatment of volumetric muscle loss in the quadriceps femoris. J. Biomech. 47, 2013–2021 (2014). https://doi.org/10.1016/j.jbiomech.2013.10.057
  81. C.H. Evans, Advances in regenerative orthopedics. Mayo Clin. Proc. 88, 1323–1339 (2013). https://doi.org/10.1016/j.mayocp.2013.04.027
  82. T. Gonzalez-Fernandez, P. Sikorski, J.K. Leach, Bio-instructive materials for musculoskeletal regeneration. Acta Biomater. 96, 20–34 (2019). https://doi.org/10.1016/j.actbio.2019.07.014
  83. H.-G. Ha, G. Han, S. Lee, K. Nam, S. Joung et al., Robot-patient registration for optical tracker-free robotic fracture reduction surgery. Comput. Methods Programs Biomed. 228, 107239 (2023). https://doi.org/10.1016/j.cmpb.2022.107239
  84. J. Liu, D. Saul, K.O. Böker, J. Ernst, W. Lehman et al., Current methods for skeletal muscle tissue repair and regeneration. BioMed Res. Int. 2018, 1984879 (2018). https://doi.org/10.1155/2018/1984879
  85. J. Yuan, F. Xin, W. Jiang, Underlying signaling pathways and therapeutic applications of pulsed electromagnetic fields in bone repair. Cell. Physiol. Biochem. 46, 1581–1594 (2018). https://doi.org/10.1159/000489206
  86. F. Shang, L. Ming, Z. Zhou, Y. Yu, J. Sun et al., The effect of licochalcone A on cell-aggregates ECM secretion and osteogenic differentiation during bone formation in metaphyseal defects in ovariectomized rats. Biomaterials 35, 2789–2797 (2014). https://doi.org/10.1016/j.biomaterials.2013.12.061
  87. Y. Liu, L. Ming, H. Luo, W. Liu, Y. Zhang et al., Integration of a calcined bovine bone and BMSC-sheet 3D scaffold and the promotion of bone regeneration in large defects. Biomaterials 34, 9998–10006 (2013). https://doi.org/10.1016/j.biomaterials.2013.09.040
  88. P. Potdar, J. Sutar, Establishment and molecular characterization of mesenchymal stem cell lines derived from human visceral & subcutaneous adipose tissues. J. Stem Cells Regen. Med. 6, 26–35 (2010). https://doi.org/10.46582/jsrm.0601005
  89. A. Marmotti, G.M. Peretti, S. Mattia, L. Mangiavini, L. de Girolamo et al., Pulsed electromagnetic fields improve tenogenic commitment of umbilical cord-derived mesenchymal stem cells: a potential strategy for tendon repair-an in vitro study. Stem Cells Int. 2018, 9048237 (2018). https://doi.org/10.1155/2018/9048237
  90. J.H. Yea, T.S. Bae, B.J. Kim, Y.W. Cho, C.H. Jo, Regeneration of the rotator cuff tendon-to-bone interface using umbilical cord-derived mesenchymal stem cells and gradient extracellular matrix scaffolds from adipose tissue in a rat model. Acta Biomater. 114, 104–116 (2020). https://doi.org/10.1016/j.actbio.2020.07.020
  91. D.R. Kwon, G.Y. Park, Y.S. Moon, S.C. Lee, Therapeutic effects of umbilical cord blood-derived mesenchymal stem cells combined with polydeoxyribonucleotides on full-thickness rotator cuff tendon tear in a rabbit model. Cell Transplant. 27, 1613–1622 (2018). https://doi.org/10.1177/0963689718799040
  92. B.-M. Seo, M. Miura, S. Gronthos, P. Mark Bartold, S. Batouli et al., Investigation of multipotent postnatal stem cells from human periodontal ligament. Lancet 364, 149–155 (2004). https://doi.org/10.1016/S0140-6736(04)16627-0
  93. P.D. Potdar, Y.D. Jethmalani, Human dental pulp stem cells: applications in future regenerative medicine. World J. Stem Cells 7, 839–851 (2015). https://doi.org/10.4252/wjsc.v7.i5.839
  94. C. Chen, Q. Shi, M. Li, Y. Chen, T. Zhang et al., Engineering an enthesis-like graft for rotator cuff repair: an approach to fabricate highly biomimetic scaffold capable of zone-specifically releasing stem cell differentiation inducers. Bioact. Mater. 16, 451–471 (2022). https://doi.org/10.1016/j.bioactmat.2021.12.021
  95. K.I. Kim, M.C. Lee, J.H. Lee, Y.W. Moon, W.S. Lee et al., Clinical efficacy and safety of the intra-articular injection of autologous adipose-derived mesenchymal stem cells for knee osteoarthritis: a phase III, randomized, double-blind, placebo-controlled trial. Am. J. Sports Med. 51, 2243–2253 (2023). https://doi.org/10.1177/03635465231179223
  96. J.R. Garza, R.E. Campbell, F.P. Tjoumakaris, K.B. Freedman, L.S. Miller et al., Clinical efficacy of intra-articular mesenchymal stromal cells for the treatment of knee osteoarthritis: a double-blinded prospective randomized controlled clinical trial. Am. J. Sports Med. 48, 588–598 (2020). https://doi.org/10.1177/0363546519899923
  97. W.S. Lee, H.J. Kim, K.I. Kim, G.B. Kim, W. Jin, Intra-articular injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of knee osteoarthritis: a phase IIb, randomized, placebo-controlled clinical trial. Stem Cells Transl. Med. 8, 504–511 (2019). https://doi.org/10.1002/sctm.18-0122
  98. J.M. Lamo-Espinosa, G. Mora, J.F. Blanco, F. Granero-Moltó, J.M. Nuñez-Córdoba et al., Intra-articular injection of two different doses of autologous bone marrow mesenchymal stem cells versus hyaluronic acid in the treatment of knee osteoarthritis: multicenter randomized controlled clinical trial (phase I/II). J. Transl. Med. 14, 246 (2016). https://doi.org/10.1186/s12967-016-0998-2
  99. C.-F. Chen, C.-C. Hu, C.-T. Wu, H.-T.H. Wu, C.-S. Chang et al., Treatment of knee osteoarthritis with intra-articular injection of allogeneic adipose-derived stem cells (ADSCs) ELIXCYTE®: a phase I/II, randomized, active-control, single-blind, multiple-center clinical trial. Stem Cell Res. Ther. 12, 562 (2021). https://doi.org/10.1186/s13287-021-02631-z
  100. L. Lu, C. Dai, Z. Zhang, H. Du, S. Li et al., Treatment of knee osteoarthritis with intra-articular injection of autologous adipose-derived mesenchymal progenitor cells: a prospective, randomized, double-blind, active-controlled, phase IIb clinical trial. Stem Cell Res. Ther. 10, 143 (2019). https://doi.org/10.1186/s13287-019-1248-3
  101. C.H. Jo, J.W. Chai, E.C. Jeong, S. Oh, P.S. Kim et al., Intratendinous injection of autologous adipose tissue-derived mesenchymal stem cells for the treatment of rotator cuff disease: a first-In-human trial. Stem Cells 36, 1441–1450 (2018). https://doi.org/10.1002/stem.2855
  102. S. Toosi, H. Naderi-Meshkin, A. Moradi, M. Daliri, V. Moghimi et al., Scaphoid bone nonunions: clinical and functional outcomes of collagen/PGA scaffolds and cell-based therapy. ACS Biomater. Sci. Eng. 9, 1928–1939 (2023). https://doi.org/10.1021/acsbiomaterials.2c00677
  103. F.G. Usuelli, M. Grassi, C. Maccario, M. Vigano’, L. Lanfranchi et al., Intratendinous adipose-derived stromal vascular fraction (SVF) injection provides a safe, efficacious treatment for Achilles tendinopathy: results of a randomized controlled clinical trial at a 6-month follow-up. Knee Surg. Sports Traumatol. Arthrosc. 26, 2000–2010 (2018). https://doi.org/10.1007/s00167-017-4479-9
  104. R.G. Thomas, A.R. Unnithan, M.J. Moon, S.P. Surendran, T. Batgerel et al., Electromagnetic manipulation enabled calcium alginate Janus microsphere for targeted delivery of mesenchymal stem cells. Int. J. Biol. Macromol. 110, 465–471 (2018). https://doi.org/10.1016/j.ijbiomac.2018.01.003
  105. G. Go, A. Yoo, H.W. Song, H.K. Min, S. Zheng et al., Multifunctional biodegradable microrobot with programmable morphology for biomedical applications. ACS Nano 15, 1059–1076 (2021). https://doi.org/10.1021/acsnano.0c07954
  106. G. Go, S.G. Jeong, A. Yoo, J. Han, B. Kang et al., Human adipose-derived mesenchymal stem cell-based medical microrobot system for knee cartilage regeneration in vivo. Sci. Robot. 5, eaay626 (2020). https://doi.org/10.1126/scirobotics.aay6626
  107. C. Xu, S. Wang, H. Wang, K. Liu, S. Zhang et al., Magnesium-based micromotors as hydrogen generators for precise rheumatoid arthritis therapy. Nano Lett. 21, 1982–1991 (2021). https://doi.org/10.1021/acs.nanolett.0c04438
  108. A. Liu, Q. Wang, Z. Zhao, R. Wu, M. Wang et al., Nitric oxide nanomotor driving exosomes-loaded microneedles for Achilles tendinopathy healing. ACS Nano 15, 13339–13350 (2021). https://doi.org/10.1021/acsnano.1c03177
  109. G. Go, J. Han, J. Zhen, S. Zheng, A. Yoo et al., A magnetically actuated microscaffold containing mesenchymal stem cells for articular cartilage repair. Adv. Healthc. Mater. 6, 201601378 (2017). https://doi.org/10.1002/adhm.201601378
  110. W.-C. Lo, C.-H. Fan, Y.-J. Ho, C.-W. Lin, C.-K. Yeh, Tornado-inspired acoustic vortex tweezer for trapping and manipulating microbubbles. Proc. Natl. Acad. Sci. U.S.A. 118, e2023188118 (2021). https://doi.org/10.1073/pnas.2023188118
  111. Q. Wang, Q. Wang, Z. Ning, K.F. Chan, J. Jiang et al., Tracking and navigation of a microswarm under laser speckle contrast imaging for targeted delivery. Sci. Robot. 9, eadh1978 (2024). https://doi.org/10.1126/scirobotics.adh1978
  112. Q. Wang, K.F. Chan, K. Schweizer, X. Du, D. Jin et al., Ultrasound doppler-guided real-time navigation of a magnetic microswarm for active endovascular delivery. Sci. Adv. 7, eabe5914 (2021). https://doi.org/10.1126/sciadv.abe5914
  113. H. Yu, Y. Huang, L. Yang, Research progress in the use of mesenchymal stem cells and their derived exosomes in the treatment of osteoarthritis. Ageing Res. Rev. 80, 101684 (2022). https://doi.org/10.1016/j.arr.2022.101684
  114. B. Chen, Y. Li, X. Zhang, F. Liu, Y. Liu et al., An efficient synthesis of ferumoxytol induced by alternating-current magnetic field. Mater. Lett. 170, 93–96 (2016). https://doi.org/10.1016/j.matlet.2016.02.006
  115. J.P. Bullivant, S. Zhao, B.J. Willenberg, B. Kozissnik, C.D. Batich et al., Materials characterization of Feraheme/ferumoxytol and preliminary evaluation of its potential for magnetic fluid hyperthermia. Int. J. Mol. Sci. 14, 17501–17510 (2013). https://doi.org/10.3390/ijms140917501
  116. G. Unsoy, S. Yalcin, R. Khodadust, G. Gunduz, U. Gunduz, Synthesis optimization and characterization of chitosan-coated iron oxide nanops produced for biomedical applications. J. Nanopart. Res. 14, 964 (2012). https://doi.org/10.1007/s11051-012-0964-8
  117. C. Guo, R.A. Gemeinhart, Understanding the adsorption mechanism of chitosan onto poly(lactide-co-glycolide) ps. Eur. J. Pharm. Biopharm. 70, 597–604 (2008). https://doi.org/10.1016/j.ejpb.2008.06.008
  118. E. Vey, C. Rodger, J. Booth, M. Claybourn, A.F. Miller et al., Degradation kinetics of poly(lactic-co-glycolic) acid block copolymer cast films in phosphate buffer solution as revealed by infrared and Raman spectroscopies. Polym. Degrad. Stab. 96, 1882–1889 (2011). https://doi.org/10.1016/j.polymdegradstab.2011.07.011
  119. U. Akgun, B. Kocaoglu, S. Ergun, M. Karahan, M. Turkmen, The effect of environmental pH change on bovine articular cartilage metabolism: implications for the use of buffered solution during arthroscopy? Knee Surg. Phys. Traumatol. Arthrosc. 22, 2843–2848 (2014). https://doi.org/10.1007/s00167-013-2441-z
  120. K. Lee, G. Go, A. Yoo, B. Kang, E. Choi et al., Wearable fixation device for a magnetically controllable therapeutic agent carrier: application to cartilage repair. Pharmaceutics 12, 593 (2020). https://doi.org/10.3390/pharmaceutics12060593
  121. L.C. Barnsley, D. Carugo, J. Owen, E. Stride, Halbach arrays consisting of cubic elements optimised for high field gradients in magnetic drug targeting applications. Phys. Med. Biol. 60, 8303–8327 (2015). https://doi.org/10.1088/0031-9155/60/21/8303
  122. G. Go, A. Yoo, S. Kim, J.K. Seon, C.S. Kim et al., Magnetization-switchable implant system to target delivery of stem cell-loaded bioactive polymeric microcarriers. Adv. Healthc. Mater. 10, e2100068 (2021). https://doi.org/10.1002/adhm.202100068
  123. J. Lee, S. Lee, S.J. Huh, B.J. Kang, H. Shin, Directed regeneration of osteochondral tissue by hierarchical assembly of spatially organized composite spheroids. Adv. Sci. 9, e2103525 (2022). https://doi.org/10.1002/advs.202103525
  124. L. Zhou, V.O. Gjvm, J. Malda, M.J. Stoddart, Y. Lai et al., Innovative tissue-engineered strategies for osteochondral defect repair and regeneration: current progress and challenges. Adv. Healthc. Mater. 9, e2001008 (2020). https://doi.org/10.1002/adhm.202001008
  125. J. Lee, H.W. Song, K.T. Nguyen, S. Kim, M. Nan et al., Magnetically actuated microscaffold with controllable magnetization and morphology for regeneration of osteochondral tissue. Micromachines 14, 434 (2023). https://doi.org/10.3390/mi14020434
  126. B.D. Smith, D.A. Grande, The Current state of scaffolds for musculoskeletal regenerative applications. Nat. Rev. Rheumatol. 11, 213–222 (2015). https://doi.org/10.1038/nrrheum.2015.27
  127. P. Duan, Z. Pan, L. Cao, Y. He, H. Wang et al., The effects of pore size in bilayered poly(lactide-co-glycolide) scaffolds on restoring osteochondral defects in rabbits. J. Biomed. Mater. Res. A 102, 180–192 (2014). https://doi.org/10.1002/jbm.a.34683
  128. X.P. Wang, X.H. Qin, C.Z. Hu, A. Terzopoulou, X.Z. Chen et al., 3D printed enzymatically biodegradable soft helical microswimmers. Adv. Funct. Mater. 28, 1804107 (2018). https://doi.org/10.1002/adfm.201804107
  129. U. Bozuyuk, O. Yasa, I.C. Yasa, H. Ceylan, S. Kizilel et al., Light-triggered drug release from 3D-printed magnetic chitosan microswimmers. ACS Nano 12, 9617–9625 (2018). https://doi.org/10.1021/acsnano.8b05997
  130. R. Pankov, K.M. Yamada, Fibronectin at a glance. J. Cell Sci. 115, 3861–3863 (2002). https://doi.org/10.1242/jcs.00059
  131. M. Ma, F. Zou, B. Abudureheman, F. Han, G. Xu et al., Magnetic microcarriers with accurate localization and proliferation of mesenchymal stem cell for cartilage defects repairing. ACS Nano 17, 6373–6386 (2023). https://doi.org/10.1021/acsnano.2c10995
  132. R. Calafiore, Alginate microcapsules for pancreatic islet cell graft immunoprotection: struggle and progress towards the final cure for type 1 diabetes mellitus. Expert Opin. Biol. Ther. 3, 201–205 (2003). https://doi.org/10.1517/14712598.3.2.201
  133. J. Zhang, B.A. Grzybowski, S. Granick, Janus p synthesis, assembly, and application. Langmuir 33, 6964–6977 (2017). https://doi.org/10.1021/acs.langmuir.7b01123
  134. Z. Chen, X.X. Song, X.L. Mu, J.K. Zhang, U.K. Cheang, 2D magnetic microswimmers for targeted cell transport and 3D cell culture structure construction. ACS Appl. Mater. Interfaces 15, 8840–8853 (2023). https://doi.org/10.1021/acsami.2c18955
  135. K. Morozov, Y. Mirzae, O. Kenneth, A. Leshansky, Dynamics of arbitrary shaped propellers driven by a rotating magnetic field. Phys. Rev. Fluids 2, 29 (2017). https://doi.org/10.1103/PhysRevFluids.2.044202
  136. S.-W. Choi, Y. Zhang, Y.-C. Yeh, A. Lake Wooten, Y. Xia, Biodegradable porous beads and their potential applications in regenerative medicine. J. Mater. Chem. 22, 11442 (2012). https://doi.org/10.1039/c2jm16019f
  137. Y. Mirzae, O. Dubrovski, O. Kenneth, K.I. Morozov, A.M. Leshansky, Geometric constraints and optimization in externally driven propulsion. Sci. Robot. 3, eaas8713 (2018). https://doi.org/10.1126/scirobotics.aas8713
  138. T. Wei, J. Liu, D. Li, S. Chen, Y. Zhang et al., Development of magnet-driven and image-guided degradable microrobots for the precise delivery of engineered stem cells for cancer therapy. Small 16, e1906908 (2020). https://doi.org/10.1002/smll.201906908
  139. G.S. Firestein, I.B. McInnes, Immunopathogenesis of rheumatoid arthritis. Immunity 46, 183–196 (2017). https://doi.org/10.1016/j.immuni.2017.02.006
  140. J.S. Smolen, D. Aletaha, I.B. McInnes, Rheumatoid arthritis. Lancet 388, 2023–2038 (2016). https://doi.org/10.1016/s0140-6736(16)30173-8
  141. L.J.S. da Fonseca, V. Nunes-Souza, M.O.F. Goulart, L.A. Rabelo, Oxidative stress in rheumatoid arthritis: what the future might hold regarding novel biomarkers and add-on therapies. Oxid. Med. Cell. Longev. 2019, 7536805 (2019). https://doi.org/10.1155/2019/7536805
  142. C.M. Weyand, Y. Shen, J.J. Goronzy, Redox-sensitive signaling in inflammatory T cells and in autoimmune disease. Free Radic. Biol. Med. 125, 36–43 (2018). https://doi.org/10.1016/j.freeradbiomed.2018.03.004
  143. I. Ohsawa, M. Ishikawa, K. Takahashi, M. Watanabe, K. Nishimaki et al., Hydrogen acts as a therapeutic antioxidant by selectively reducing cytotoxic oxygen radicals. Nat. Med. 13, 688–694 (2007). https://doi.org/10.1038/nm1577
  144. Y. Wu, M. Yuan, J. Song, X. Chen, H. Yang, Hydrogen gas from inflammation treatment to cancer therapy. ACS Nano 13, 8505–8511 (2019). https://doi.org/10.1021/acsnano.9b05124
  145. X. Xu, X. He, J. Liu, J. Qin, J. Ye et al., Protective effects of hydrogen-rich saline against renal ischemia-reperfusion injury by increased expression of heme oxygenase-1 in aged rats. Int. J. Clin. Exp. Pathol. 12, 1488–1496 (2019), PMID: 31933966; PMCID: PMC6947057
  146. K. Liu, J. Ou, S. Wang, J. Gao, L. Liu et al., Magnesium-based micromotors for enhanced active and synergistic hydrogen chemotherapy. Appl. Mater. Today 20, 100694 (2020). https://doi.org/10.1016/j.apmt.2020.100694
  147. J. Meng, P. Yu, H. Jiang, T. Yuan, N. Liu et al., Molecular hydrogen decelerates rheumatoid arthritis progression through inhibition of oxidative stress. Am. J. Transl. Res. 8, 4472–4477 (2016), PMID: 27830032; PMCID: PMC5095341
  148. H. Sies, V.V. Belousov, N.S. Chandel, M.J. Davies, D.P. Jones et al., Defining roles of specific reactive oxygen species (ROS) in cell biology and physiology. Nat. Rev. Mol. Cell Biol. 23, 499–515 (2022). https://doi.org/10.1038/s41580-022-00456-z
  149. T. Wu, Y. Liu, Y. Cao, Z. Liu, Engineering macrophage exosome disguised biodegradable nanoplatform for enhanced sonodynamic therapy of glioblastoma. Adv. Mater. 34, e2110364 (2022). https://doi.org/10.1002/adma.202110364
  150. L. Zhang, Q.-C. Yang, S. Wang, Y. Xiao, S.-C. Wan et al., Engineering multienzyme-mimicking covalent organic frameworks as pyroptosis inducers for boosting antitumor immunity. Adv. Mater. 34, e2108174 (2022). https://doi.org/10.1002/adma.202108174
  151. D. Tang, R.S. Tare, L.-Y. Yang, D.F. Williams, K.-L. Ou et al., Biofabrication of bone tissue: approaches, challenges and translation for bone regeneration. Biomaterials 83, 363–382 (2016). https://doi.org/10.1016/j.biomaterials.2016.01.024
  152. Y.-W. Zhang, M.-M. Cao, Y.-J. Li, P.-P. Lu, G.-C. Dai et al., Fecal microbiota transplantation ameliorates bone loss in mice with ovariectomy-induced osteoporosis via modulating gut microbiota and metabolic function. J. Orthop. Translat. 37, 46–60 (2022). https://doi.org/10.1016/j.jot.2022.08.003
  153. Y.-W. Zhang, M.-M. Cao, Y.-J. Li, G.-C. Dai, P.-P. Lu et al., The regulative effect and repercussion of probiotics and prebiotics on osteoporosis: involvement of brain-gut-bone axis. Crit. Rev. Food Sci. Nutr. 63, 7510–7528 (2023). https://doi.org/10.1080/10408398.2022.2047005
  154. D. Cao, J.G. Martinez, E.S. Hara, E.W.H. Jager, Biohybrid variable-stiffness soft actuators that self-create bone. Adv. Mater. 34, e2107345 (2022). https://doi.org/10.1002/adma.202107345
  155. A.V. Singh, M.H. Dad Ansari, C.B. Dayan, J. Giltinan, S. Wang et al., Multifunctional magnetic hairbot for untethered osteogenesis, ultrasound contrast imaging and drug delivery. Biomaterials 219, 119394 (2019). https://doi.org/10.1016/j.biomaterials.2019.119394
  156. A. Yamauchi, K. Yamauchi, New aspects of the structure of human scalp hair-II: Tubular structure and material flow property of the medulla. J. Cosmetic Sci. 69(1), 19–33 (2018), PMID: 29658875.
  157. C.E. Hoyle, A.B. Lowe, C.N. Bowman, Thiol-click chemistry: a multifaceted toolbox for small molecule and polymer synthesis. Chem. Soc. Rev. 39, 1355–1387 (2010). https://doi.org/10.1039/B901979K
  158. Y. Deng, X. Liu, A. Xu, L. Wang, Z. Luo et al., Effect of surface roughness on osteogenesis in vitro and osseointegration in vivo of carbon fiber-reinforced polyetheretherketone-nanohydroxyapatite composite. Int. J. Nanomedicine 10, 1425–1447 (2015). https://doi.org/10.2147/IJN.S75557
  159. L.A. Goldsmith, H.P. Baden, The mechanical properties of hair I. the dynamic sonic modulus. J. Investig. Dermatol. 55(4), 256–259 (1970). https://doi.org/10.1111/1523-1747.ep12259955
  160. A.J. Engler, S. Sen, H.L. Sweeney, D.E. Discher, Matrix elasticity directs stem cell lineage specification. Cell 126, 677–689 (2006). https://doi.org/10.1016/j.cell.2006.06.044
  161. I.C. Yasa, A.F. Tabak, O. Yasa, H. Ceylan, M. Sitti, 3D-printed microrobotic transporters with recapitulated stem cell niche for programmable and active cell delivery. Adv. Funct. Mater. 29, 1808992 (2019). https://doi.org/10.1002/adfm.201808992
  162. A. Marino, C. Filippeschi, G.G. Genchi, V. Mattoli, B. Mazzolai et al., The Osteoprint: a bioinspired two-photon polymerized 3-D structure for the enhancement of bone-like cell differentiation. Acta Biomater. 10, 4304–4313 (2014). https://doi.org/10.1016/j.actbio.2014.05.032
  163. J. Li, X. Li, T. Luo, R. Wang, C. Liu et al., Development of a magnetic microrobot for carrying and delivering targeted cells. Sci. Robot. 3, eaat8829 (2018). https://doi.org/10.1126/scirobotics.aat8829
  164. J. Li, L. Fan, Y. Li, T. Wei, C. Wang et al., Development of cell-carrying magnetic microrobots with bioactive nanostructured titanate surface for enhanced cell adhesion. Micromachines 12, 1572 (2021). https://doi.org/10.3390/mi12121572
  165. S. Liu, Y. Zhu, H. Gao, P. Ge, K. Ren et al., One-step fabrication of functionalized poly(etheretherketone) surfaces with enhanced biocompatibility and osteogenic activity. Mater. Sci. Eng. C Mater. Biol. Appl. 88, 70–78 (2018). https://doi.org/10.1016/j.msec.2018.03.003
  166. Y. Hu, J. Ran, Z. Zheng, Z. Jin, X. Chen et al., Exogenous stromal derived factor-1 releasing silk scaffold combined with intra-articular injection of progenitor cells promotes bone-ligament-bone regeneration. Acta Biomater. 71, 168–183 (2018). https://doi.org/10.1016/j.actbio.2018.02.019
  167. M.-J. Shen, C.-Y. Wang, D.-X. Hao, J.-X. Hao, Y.-F. Zhu et al., Multifunctional nanomachinery for enhancement of bone healing. Adv. Mater. 34, e2107924 (2022). https://doi.org/10.1002/adma.202107924
  168. W. Chaikittisilp, Y. Yamauchi, K. Ariga, Material evolution with nanotechnology, nanoarchitectonics, and materials informatics: what will be the next paradigm shift in nanoporous materials? Adv. Mater. 34, e2107212 (2022). https://doi.org/10.1002/adma.202107212
  169. B. Wang, K. Kostarelos, B.J. Nelson, L. Zhang, Trends in micro-/ nanorobotics: materials development, actuation, localization, and system integration for biomedical applications. Adv. Mater. 33, e2002047 (2021). https://doi.org/10.1002/adma.202002047
  170. J. Li, W. Liu, T. Li, I. Rozen, J. Zhao et al., Swimming microrobot optical nanoscopy. Nano Lett. 16, 6604–6609 (2016). https://doi.org/10.1021/acs.nanolett.6b03303
  171. H. Hoppeler, M. Flück, Normal mammalian skeletal muscle and its phenotypic plasticity. J. Exp. Biol. 205, 2143–2152 (2002). https://doi.org/10.1242/jeb.205.15.2143
  172. M.M. Smoak, A.G. Mikos, Advances in biomaterials for skeletal muscle engineering and obstacles still to overcome. Mater. Today Bio 7, 100069 (2020). https://doi.org/10.1016/j.mtbio.2020.100069
  173. Y. Jin, D. Shahriari, E.J. Jeon, S. Park, Y.S. Choi et al., Functional skeletal muscle regeneration with thermally drawn porous fibers and reprogrammed muscle progenitors for volumetric muscle injury. Adv. Mater. 33, e2007946 (2021). https://doi.org/10.1002/adma.202007946
  174. I. Eugenis, D. Wu, T.A. Rando, Cells, scaffolds, and bioactive factors: engineering strategies for improving regeneration following volumetric muscle loss. Biomaterials 278, 121173 (2021). https://doi.org/10.1016/j.biomaterials.2021.121173
  175. S. Han, S.H. Cruz, S. Park, S.R. Shin, Nano-biomaterials and advanced fabrication techniques for engineering skeletal muscle tissue constructs in regenerative medicine. Nano Converg. 10, 48 (2023). https://doi.org/10.1186/s40580-023-00398-y
  176. W. Zhuge, X. Ding, W. Zhang, D. Zhang, H. Wang et al., Microfluidic generation of helical micromotors for muscle tissue engineering. Chem. Eng. J. 447, 137455 (2022). https://doi.org/10.1016/j.cej.2022.137455
  177. Y. Yu, J. Guo, Y. Wang, C. Shao, Y. Wang et al., Bioinspired helical micromotors as dynamic cell microcarriers. ACS Appl. Mater. Interfaces 12, 16097–16103 (2020). https://doi.org/10.1021/acsami.0c01264
  178. L.T. Denes, L.A. Riley, J.R. Mijares, J.D. Arboleda, K. McKee et al., Culturing C2C12 myotubes on micromolded gelatin hydrogels accelerates myotube maturation. Skelet. Muscle 9, 17 (2019). https://doi.org/10.1186/s13395-019-0203-4
  179. T. Asano, T. Ishizuka, K. Morishima, H. Yawo, Optogenetic induction of contractile ability in immature C2C12 myotubes. Sci. Rep. 5, 8317 (2015). https://doi.org/10.1038/srep08317
  180. T. Asano, H. Igarashi, T. Ishizuka, H. Yawo, Organelle optogenetics: direct manipulation of intracellular Ca2+ dynamics by light. Front. Neurosci. 12, 561 (2018). https://doi.org/10.3389/fnins.2018.00561
  181. L. Liu, J. Wu, B. Chen, J. Gao, T. Li et al., Magnetically actuated biohybrid microswimmers for precise photothermal muscle contraction. ACS Nano 16, 6515–6526 (2022). https://doi.org/10.1021/acsnano.2c00833
  182. T. Bito, M. Bito, Y. Asai, S. Takenaka, Y. Yabuta et al., Characterization and quantitation of vitamin B12 compounds in various Chlorella supplements. J. Agric. Food Chem. 64, 8516–8524 (2016). https://doi.org/10.1021/acs.jafc.6b03550
  183. D. Chen, Q. Tang, X. Li, X. Zhou, J. Zang et al., Biocompatibility of magnetic Fe3O4 nanops and their cytotoxic effect on MCF-7 cells. Int. J. Nanomedicine 7, 4973–4982 (2012). https://doi.org/10.2147/IJN.S35140
  184. J. Sun, S. Zhou, P. Hou, Y. Yang, J. Weng et al., Synthesis and characterization of biocompatible Fe3O4 nanops. J. Biomed. Mater. Res. A 80, 333–341 (2007). https://doi.org/10.1002/jbm.a.30909
  185. M. Abboud, S. Youssef, J. Podlecki, R. Habchi, G. Germanos et al., Superparamagnetic Fe3O4 nanops, synthesis and surface modification. Mater. Sci. Semicond. Process. 39, 641–648 (2015). https://doi.org/10.1016/j.mssp.2015.05.035
  186. K.G. Silbernagel, R. Thomeé, B.I. Eriksson, J. Karlsson, Continued sports activity, using a pain-monitoring model, during rehabilitation in patients with Achilles tendinopathy. Am. J. Phys. Med. 35, 897–906 (2007). https://doi.org/10.1177/0363546506298279
  187. S. de Jonge, C. van den Berg, R.J. de Vos, H.J. van der Heide, A. Weir et al., Incidence of midportion Achilles tendinopathy in the general population. Br. J. Sports Med. 45, 1026–1028 (2011). https://doi.org/10.1136/bjsports-2011-090342
  188. K. Lee, Y. Xue, J. Lee, H.-J. Kim, Y. Liu et al., A patch of detachable hybrid microneedle depot for localized delivery of mesenchymal stem cells in regeneration therapy. Adv. Funct. Mater. 30, 2000086 (2020). https://doi.org/10.1002/adfm.202000086
  189. N.L. Millar, G.A.C. Murrell, I.B. McInnes, Inflammatory mechanisms in tendinopathy–towards translation. Nat. Rev. Rheumatol. 13, 110–122 (2017). https://doi.org/10.1038/nrrheum.2016.213
  190. C.J. Pearce, M. Ismail, J.D. Calder, Is apoptosis the cause of noninsertional Achilles tendinopathy? Am. J. Sports Med. 37, 2440–2444 (2009). https://doi.org/10.1177/0363546509340264
  191. A.A. Solovev, Y. Mei, E. Bermúdez Ureña, G. Huang, O.G. Schmidt, Catalytic microtubular jet engines self-propelled by accumulated gas bubbles. Small 5, 1688–1692 (2009). https://doi.org/10.1002/smll.200900021
  192. M.E. Ibele, P.E. Lammert, V.H. Crespi, A. Sen, Emergent, collective oscillations of self-mobile ps and patterned surfaces under redox conditions. ACS Nano 4, 4845–4851 (2010). https://doi.org/10.1021/nn101289p
  193. W.F. Paxton, P.T. Baker, T.R. Kline, Y. Wang, T.E. Mallouk et al., Catalytically induced electrokinetics for motors and micropumps. J. Am. Chem. Soc. 128, 14881–14888 (2006). https://doi.org/10.1021/ja0643164
  194. H. Zhang, W. Duan, L. Liu, A. Sen, Depolymerization-powered autonomous motors using biocompatible fuel. J. Am. Chem. Soc. 135, 15734–15737 (2013). https://doi.org/10.1021/ja4089549
  195. J. Ou, H. Tian, J. Wu, J. Gao, J. Jiang et al., MnO2-based nanomotors with active Fenton-like Mn2+ delivery for enhanced chemodynamic therapy. ACS Appl. Mater. Interfaces 13, 38050–38060 (2021). https://doi.org/10.1021/acsami.1c08926
  196. J.R. Howse, R.A.L. Jones, A.J. Ryan, T. Gough, R. Vafabakhsh et al., Self-motile colloidal ps: from directed propulsion to random walk. Phys. Rev. Lett. 99, 048102 (2007). https://doi.org/10.1103/PhysRevLett.99.048102
  197. A. Ghosh, P. Fischer, Controlled propulsion of artificial magnetic nanostructured propellers. Nano Lett. 9, 2243–2245 (2009). https://doi.org/10.1021/nl900186w
  198. L. Zhang, J.J. Abbott, L. Dong, B.E. Kratochvil, D. Bell et al., Artificial bacterial flagella: fabrication and magnetic control. Appl. Phys. Lett. 94, 3 (2009). https://doi.org/10.1063/1.3079655
  199. S. Jeon, S. Kim, S. Ha, S. Lee, E. Kim et al., Magnetically actuated microrobots as a platform for stem cell transplantation. Sci. Robot. 4, eaav4317 (2019). https://doi.org/10.1126/scirobotics.aav4317
  200. X.-Z. Chen, J.-H. Liu, M. Dong, L. Müller, G. Chatzipirpiridis et al., Magnetically driven piezoelectric soft microswimmers for neuron-like cell delivery and neuronal differentiation. Mater. Horiz. 6, 1512–1516 (2019). https://doi.org/10.1039/C9MH00279K
  201. C.E. Touw, B. Nemeth, A.M.R. Rondon, R.A. van Adrichem, T. Lisman et al., Lower-leg injury and knee arthroscopy have distinct effects on coagulation. Blood Adv. 6, 5232–5243 (2022). https://doi.org/10.1182/bloodadvances.2022007828
  202. J. Ramos, C. Perrotta, G. Badariotti, G. Berenstein, Interventions for preventing venous thromboembolism in adults undergoing knee arthroscopy. Cochrane Database Syst. Rev. (2007). https://doi.org/10.1002/14651858.CD005259.pub2
  203. Y. Mohammed, C.E. Touw, B. Nemeth, R.A. van Adrichem, C.H. Borchers et al., Targeted proteomics for evaluating risk of venous thrombosis following traumatic lower-leg injury or knee arthroscopy. J. Thromb. Haemost. 20, 684–699 (2022). https://doi.org/10.1111/jth.15623
  204. C.E. Touw, B. Nemeth, R.A. van Adrichem, I.B. Schipper, R.G.H.H. Nelissen et al., The influence of lower-leg injury and knee arthroscopy on natural anticoagulants and fibrinolysis. J. Thromb. Haemost. 21, 227–236 (2023). https://doi.org/10.1016/j.jtha.2022.11.006
  205. Q. Wang, X. Du, D. Jin, L. Zhang, Real-time ultrasound Doppler tracking and autonomous navigation of a miniature helical robot for accelerating thrombolysis in dynamic blood flow. ACS Nano 16, 604–616 (2022). https://doi.org/10.1021/acsnano.1c07830
  206. N.A. Haq-Siddiqi, D. Britton, J. Kim, Montclare Protein-engineered biomaterials for cartilage therapeutics and repair. Adv. Drug Deliv. Rev. 192, 114647 (2023). https://doi.org/10.1016/j.addr.2022.114647
  207. S. Che, J. Zhang, F. Mou, X. Guo, J.E. Kauffman et al., Light-programmable assemblies of isotropic micromotors. Research 2022, 9816562 (2022). https://doi.org/10.34133/2022/9816562
  208. J. Liu, L. Li, C. Cao, Z. Feng, Y. Liu et al., Swarming multifunctional heater-thermometer nanorobots for precise feedback hyperthermia delivery. ACS Nano 17, 16731–16742 (2023). https://doi.org/10.1021/acsnano.3c03131
  209. L. Li, Z. Yu, J. Liu, M. Yang, G. Shi et al., Swarming responsive photonic nanorobots for motile-targeting microenvironmental mapping and mapping-guided photothermal treatment. Nano-Micro Lett. 15, 141 (2023). https://doi.org/10.1007/s40820-023-01095-5
  210. M. Yang, X. Guo, F. Mou, J. Guan, Lighting up micro-/nanorobots with fluorescence. Chem. Rev. 123, 3944–3975 (2023). https://doi.org/10.1021/acs.chemrev.2c00062
  211. M. Yang, Y. Zhang, F. Mou, C. Cao, L. Yu et al., Swarming magnetic nanorobots bio-interfaced by heparinoid-polymer brushes for in vivo safe synergistic thrombolysis. Sci. Adv. 9, eadk7251 (2023). https://doi.org/10.1126/sciadv.adk7251
  212. R.C. Nordberg, G.A. Otarola, D. Wang, J.C. Hu, K.A. Athanasiou, Navigating regulatory pathways for translation of biologic cartilage repair products. Sci. Transl. Med. 14, eabp8163 (2022). https://doi.org/10.1126/scitranslmed.abp8163
Read More
Author biographies are not available.
Download this PDF file
PDF
Statistic
Read Counter : 3245 Download : 2440

Most read articles by the same author(s)

1 2 3 > >>