Structurally and Functionally Adaptive Biomimetic Periosteum: Materials, Fabrication, and Construction Strategies

Abstract

The periosteum is crucial in the processes of bone formation, regeneration, and remodelling. Specifically, periosteal progenitor cells contribute a major force to the initiation of bone healing. Biomimetic periosteum (BP), employed for treating bone defects, exhibits superior outcomes in terms of bone integrity, proper vascularization, and minimal heterotopic ossification when compared to conventional direct graft bone void fillers. Therefore, BP has emerged as a contemporary and effective approach for addressing bone defects. As an in vivo graft, BP necessitates excellent biocompatibility and appropriate mechanical properties. Furthermore, it should closely mirror the architecture and functionality of the natural periosteum. This review provides a detailed summary of recent research progress on BP, incorporating inspiring studies that contribute to the future development of this field. Initially, the review examines the structure and function of the periosteum in the context of bone defect repair. Subsequently, it analyzes the current research and design concept for BP construction and provides a comprehensive overview of the materials and techniques employed in constructing BP. Finally, it summarizes the construction strategies of BP used for treating bone defects from various perspectives including structural and functional biomimicry, and discusses the latest advances in current research.

Keywords

biomimetic periosteum / biomimicry / bone defect repair / materials / techniques

References

[1] Y. Yang, J. Rao, H. Liu, et al., “Biomimicking Design of Artificial Periosteum for Promoting Bone Healing,” Journal of Orthopaedic Translation 36 (2022): 18-32.

[2] W. Zhang, N. Wang, M. Yang, et al., “Periosteum and Development of the Tissue-Engineered Periosteum for Guided Bone Regeneration,” Journal of Orthopaedic Translation 33 (2022): 41-54.

[3] Q. Wang, J. Xu, H. Jin, et al., “Artificial Periosteum in Bone Defect Repair—A Review,” Chinese Chemical Letters 28 (2017): 1801-1807.

[4] M. D. Hoffman and D. S. W. Benoit, “Emerging Ideas: Engineering the Periosteum: Revitalizing Allografts by Mimicking Autograft Healing,” Clinical Orthopaedics & Related Research 471 (2013): 721-726.

[5] S. Tariq, S. A. Shah, F. Hameed, et al., “Tissue Engineered Periosteum: Fabrication of a Gelatin Basedtrilayer Composite Scaffold With Biomimetic Properties for Enhanced Bone Healing,” International Journal of Biological Macromolecules 263 (2024): 130371.

[6] N. Li, J. Song, G. Zhu, et al., “Periosteum Tissue Engineering—A Review,” Biomaterials Science 4 (2016): 1554-1561.

[7] Y. Chen, X. Jin, J. Lu, et al., “Enzyme-Photodynamic Adaptive Bionic Periosteum for Bone Revitalization,” Advanced Functional Materials 34 (2024): 2314120.

[8] S. F. Evans, J. B. Parent, C. E. Lasko, et al., “Periosteum, Bone's “Smart” Bounding Membrane, Exhibits Direction-Dependent Permeability,” Journal of Bone and Mineral Research 28 (2013): 608-617.

[9] X. Zhao, Y. Zhuang, Y. Cao, et al., “Electrospun Biomimetic Periosteum Capable of Controlled Release of Multiple Agents for Programmed Promoting Bone Regeneration,” Advanced Healthcare Materials 13 (2024): 2303134.

[10] Z. Assadi, P. Rezvanian, Z. Gounani, F. Ejeian, A. Zarrabi, and E. Masaeli, “Multilayered Nanocomposite Membrane Orchestrating Targeted Dual Release Strategies for Enhanced Guided Bone Regeneration,” Chemical Engineering Journal 484 (2024): 149237.

[11] Y. Zhao, W. Sun, X. Wu, et al., “Janus Membrane with Intrafibrillarly Strontium-Apatite-Mineralized Collagen for Guided Bone Regeneration,” ACS Nano 18, no. 9 (2024): 7204-7222.

[12] S. Wu, S. Luo, Z. Cen, et al., “All-In-One Porous Membrane Enables Full Protection in Guided Bone Regeneration,” Nature Communication 15 (2024): 119.

[13] C. Huang, C. Chi, Y. Zhao, et al., “A Periosteum-Bioinspired Electrospun Janus Membrane With Antibacterial and Osteogenic Dual Function,” Macromolecular Bioscience 24 (2024): 2300501.

[14] J. Long, W. Zhang, Y. Chen, et al., “Multifunctional Magnesium Incorporated Scaffolds by 3D-Printing for Comprehensive Postsurgical Management of Osteosarcoma,” Biomaterials 275 (2021): 120950.

[15] F. Elefteriou, “Impact of the Autonomic Nervous System on the Skeleton,” Physiological Reviews 98 (2018): 1083-1112.

[16] A. Marrella, T. Y. Lee, D. H. Lee, et al., “Engineering Vascularized and Innervated Bone Biomaterials for Improved Skeletal Tissue Regeneration,” Materials Today 21 (2018): 362-376.

[17] Y. Lou, H. Wang, G. Ye, et al., “Periosteal Tissue Engineering: Current Developments and Perspectives,” Advanced Healthcare Materials 10 (2021): 2100215.

[18] G. Augustin, A. Antabak, and S. Davila, “RETRACTED: The Periosteum,” Injury 38 (2007): 1115-1130.

[19] H. Chang and M. L. Knothe Tate, “Concise Review: The Periosteum: Tapping Into a Reservoir of Clinically Useful Progenitor Cells,” Stem Cells Translational Medicine 1 (2012): 480-491.

[20] B. Gao, R. Deng, Y. Chai, et al., “Macrophage-Lineage TRAP+ Cells Recruit Periosteum-Derived Cells for Periosteal Osteogenesis and Regeneration,” Journal of Clinical Investigation 129 (2019): 2578-2594.

[21] G. He, Y. Shi, J. Lim, T. Bellido, J. Ni, and F. Long, “Differential Involvement of Wnt Signaling in Bmp Regulation of Cancellous Versus Periosteal Bone Growth,” Bone Research 5 (2017): 1-11.

[22] C. Wang, J. A. Inzana, A. J. Mirando, et al., “NOTCH Signaling in Skeletal Progenitors Is Critical for Fracture Repair,” Journal of Clinical Investigation 126 (2016): 1471-1481.

[23] Q. Qin, S. Lee, N. Patel, et al., “Pancreatic Regulation of Glucose Homeostasis,” Experimental & Molecular Medicine 54 (2022): 1844-1849.

[24] F. Karl, T. Bischler, N. Egenolf, D. Evdokimov, T. Heckel, and N. Üçeyler, “Fibromyalgia vs Small Fiber Neuropathy: Diverse Keratinocyte Transcriptome Signature,” Pain 162 (2021): 2569-2577.

[25] R. E. Tomlinson, Z. Li, Z. Li, et al., “NGF-TrkA Signaling in Sensory Nerves is Required for Skeletal Adaptation to Mechanical Loads in Mice,” Proceedings of the National Academy of Sciences 114 (2017): E3632-E3641.

[26] U. Lerner and E. Persson, “Osteotropic Effects by the Neuropeptides Calcitonin Gene-Related Peptide, Substance P and Vasoactive Intestinal Peptide,” Journal of Musculoskeletal & Neuronal Interactions 8 (2008): 154-165.

[27] Y. Konttinen, S. Imai, and A. Suda, “Neuropeptides and the Puzzle of Bone Remodeling: State of the Art,” Acta Orthopaedica Scandinavica 67 (1996): 632-639.

[28] S. J. Roberts, N. van Gastel, G. Carmeliet, and F. P. Luyten, “Uncovering the Periosteum for Skeletal Regeneration: The Stem Cell That Lies Beneath,” Bone 70 (2015): 10-18.

[29] X. Wei, M. Hu, Y. Mishina, and F. Liu, “Developmental Regulation of the Growth Plate and Cranial Synchondrosis,” Journal of Dental Research 95 (2016): 1221-1229.

[30] D. Lopes, C. Martins-Cruz, M. B. Oliveira, and J. F. Mano, “Bone Physiology as Inspiration for Tissue Regenerative Therapies,” Biomaterials 185 (2018): 240-275.

[31] J. R. Dwek, “The Periosteum: What is it, Where is it, and What Mimics It in Its Absence?,” Skeletal Radiology 39 (2010): 319-323.

[32] O. Duchamp de Lageneste, A. Julien, R. Abou-Khalil, et al., “Periosteum Contains Skeletal Stem Cells With High Bone Regenerative Potential Controlled by Periostin,” Nature Communications 9 (2018): 733.

[33] Y.-K. Kim, H. Nakata, M. Yamamoto, M. Miyasaka, S. Kasugai, and S. Kuroda, “Osteogenic Potential of Mouse Periosteum-Derived Cells Sorted for CD90 In Vitro and In Vivo,” Stem Cells Translational Medicine 5 (2016): 227-234.

[34] J. E. Aaron, “Periosteal Sharpey's Fibers: A Novel Bone Matrix Regulatory System?,” Frontiers in Endocrinology 3 (2012): 98.

[35] M.-N. Hsu, F.-J. Yu, Y.-H. Chang, et al., “CRISPr Interference-Mediated Noggin Knockdown Promotes BMP2-Induced Osteogenesis and Calvarial Bone Healing,” Biomaterials 252 (2020): 120094.

[36] M. R. Allen, J. M. Hock, and D. B. Burr, “Periosteum: Biology, Regulation, and Response to Osteoporosis Therapies,” Bone 35 (2004): 1003-1012.

[37] T. Nobuto, F. Suwa, T. Kono, et al., “Microvascular Response in the Periosteum Following Mucoperiosteal Flap Surgery in Dogs: Angiogenesis and Bone Resorption and Formation,” Journal of Periodontology 76 (2005): 1346-1353.

[38] F. Qiao, Y. Zou, B. Bie, and Y. Lv, “Dual siRNA-Loaded Cell Membrane Functionalized Matrix Facilitates Bone Regeneration With Angiogenesis and Neurogenesis,” Small 20 (2024): 2307062.

[39] S. Guo and C. He, “Bioprinted Scaffold Remodels the Neuromodulatory Microenvironment for Enhancing Bone Regeneration,” Advanced Functional Materials 33 (2023): 2304172.

[40] Y. Zhang, J. Xu, Y. C. Ruan, et al., “Implant-Derived Magnesium Induces Local Neuronal Production of CGRP to Improve Bone-Fracture Healing in Rats,” Nature Medicine 22 (2016): 1160-1169.

[41] Y. Li, J. Xu, J. Mi, et al., “Biodegradable Magnesium Combined with Distraction Osteogenesis Synergistically Stimulates Bone Tissue Regeneration via CGRP-FAK-VEGF Signaling Axis,” Biomaterials 275 (2021): 120984.

[42] J. Wang, J. Xu, X. Wang, et al., “Magnesium-Pretreated Periosteum for Promoting Bone-Tendon Healing After Anterior Cruciate Ligament Reconstruction,” Biomaterials 268 (2021): 120576.

[43] S. Yang, Z. Chen, P. Zhuang, et al., “Seamlessly Adhesive Bionic Periosteum Patches Via Filling Microcracks for Defective Bone Healing,” Small Methods 7 (2023): 2300370.

[44] M. Zhu, H. Ye, J. Fang, et al., “Engineering High-Resolution Micropatterns Directly Onto Titanium With Optimized Contact Guidance to Promote Osteogenic Differentiation and Bone Regeneration,” ACS Applied Materials & Interfaces 11 (2019): 43888-43901.

[45] Z. Zhou, Y. Liu, W. Li, et al., “A Self-Adaptive Biomimetic Periosteum Employing Nitric Oxide Release for Augmenting Angiogenesis in Bone Defect Regeneration,” Advanced Healthcare Materials 13 (2023): 2302153.

[46] C. H. Turner, M. R. Forwood, and M. W. Otter, “Mechanotransduction in Bone: Do Bone Cells Act as Sensors of Fluid Flow?,” FASEB Journal 8 (1994): 875-878.

[47] J. Klein-Nulend, E. H. Burger, C. M. Semeins, L. G. Raisz, and C. C. Pilbeam, “Pulsating Fluid Flow Stimulates Prostaglandin Release and Inducible Prostaglandin G/H Synthase mRNA Expression in Primary Mouse Bone Cells,” Journal of Bone and Mineral Research 12 (2009): 45-51.

[48] D. A. Weston, “Investigating the Specificity of Periosteal Reactions in Pathology Museum Specimens,” American Journal of Physical Anthropology 137 (2008): 48-59.

[49] B. D. Ragsdale, J. E. Madewell, and D. E. Sweet, “Radiologic and Pathologic Analysis of Solitary Bone Lesions,” Radiologic Clinics of North America 19 (1981): 749-783.

[50] X. Shi, T. Fujie, A. Saito, et al., “Periosteum-Mimetic Structures Made From Freestanding Microgrooved Nanosheets,” Advanced Materials 26 (2014): 3290-3296.

[51] W. Zhang, X. Wang, R. Zhang, et al., “Effects of Integrated Bioceramic and Uniaxial Drawing on Mechanically-Enhanced Fibrogenesis for Bionic Periosteum Engineering,” Colloids and Surfaces B: Biointerfaces 214 (2022): 112459.

[52] F. Zhao, C. Zhang, J. Liu, et al., “Periosteum Structure/Function-Mimicking Bioactive Scaffolds With Piezoelectric/Chem/Nano Signals for Critical-Sized Bone Regeneration,” Chemical Engineering Journal 402 (2020): 126203.

[53] M. Gong, C. Huang, Y. Huang, et al., “Core-Sheath Micro/Nano Fiber Membrane With Antibacterial and Osteogenic Dual Functions as Biomimetic Artificial Periosteum for Bone Regeneration Applications,” Nanomedicine: Nanotechnology, Biology and Medicine 17 (2019): 124-136.

[54] C. W. Cheng, L. D. Solorio, and E. Alsberg, “Decellularized Tissue and Cell-Derived Extracellular Matrices as Scaffolds for Orthopaedic Tissue Engineering,” Biotechnology Advances 32 (2014): 462-484.

[55] K. Chen, X. Lin, Q. Zhang, et al., “Decellularized Periosteum as a Potential Biologic Scaffold for Bone Tissue Engineering,” Acta Biomaterialia 19 (2015): 46-55.

[56] X. Lin, C. Zhao, P. Zhu, et al., “Periosteum Extracellular-Matrix-Mediated Acellular Mineralization During Bone Formation,” Advanced Healthcare Materials 7 (2018): 1700660.

[57] S. Li, R. Deng, T. Forouzanfar, G. Wu, D. Quan, and M. Zhou, “Decellularized Periosteum-Derived Hydrogels Promote the Proliferation, Migration and Osteogenic Differentiation of Human Umbilical Cord Mesenchymal Stem Cells,” Gels 8 (2022): 294.

[58] G. Cheng, S. Guo, M. Li, S. Xiao, B. Jiang, and Y. Ding, “Hydroxyapatite-Coated Small Intestinal Submucosa Membranes Enhanced Periodontal Tissue Regeneration Through Immunomodulation and Osteogenesis via BMP-2/Smad Signaling Pathway,” Advanced Healthcare Materials 13 (2023): 2301479.

[59] D. S. M. Dziedzic, J. C. Francisco, B. F. Mogharbel, et al., “Combined Biomaterials: Amniotic Membrane and Adipose Tissue to Restore Injured Bone as Promoter of Calcification in Bone Regeneration: Preclinical Model,” Calcified Tissue International 108 (2021): 667-679.

[60] S. Ghanmi, M. Trigui, W. Baya, et al., “The Periosteum-Like Effect of Fresh Human Amniotic Membrane on Bone Regeneration in a Rabbit Critical-Sized Defect Model,” Bone 110 (2018): 392-404.

[61] B. Schonmeyr, N. Clavin, T. Avraham, V. Longo, and B. J. Mehrara, “Synthesis of a Tissue-Engineered Periosteum With Acellular Dermal Matrix and Cultured Mesenchymal Stem Cells,” Tissue Engineering Part A 15 (2009): 1833-1841.

[62] H. Lu, T. Hoshiba, N. Kawazoe, I. Koda, M. Song, and G. Chen, “Cultured Cell-Derived Extracellular Matrix Scaffolds for Tissue Engineering,” Biomaterials 32 (2011): 9658-9666.

[63] W. Zhang, Y. Zhu, J. Li, et al., “Cell-Derived Extracellular Matrix: Basic Characteristics and Current Applications in Orthopedic Tissue Engineering,” Tissue Engineering Part B: Reviews 22 (2016): 193-207.

[64] K. Dzobo, T. Turnley, A. Wishart, et al., “Fibroblast-Derived Extracellular Matrix Induces Chondrogenic Differentiation in Human Adipose-Derived Mesenchymal Stromal/Stem Cells In Vitro,” International Journal of Molecular Sciences 17 (2016): 1259.

[65] Y. Yu, Y. Wang, W. Zhang, et al., “Biomimetic Periosteum-Bone Substitute Composed of Preosteoblast-Derived Matrix and Hydrogel for Large Segmental Bone Defect Repair,” Acta Biomaterialia 113 (2020): 317-327.

[66] J. Zhang, Y. Huang, Y. Wang, J. Xu, T. Huang, and X. Luo, “Construction of Biomimetic Cell-Sheet-Engineered Periosteum With a Double Cell Sheet to Repair Calvarial Defects of Rats,” Journal of Orthopaedic Translation 38 (2023): 1-11.

[67] T. Long, Z. Zhu, H. A. Awad, E. M. Schwarz, M. J. Hilton, and Y. Dong, “The Effect of Mesenchymal Stem Cell Sheets on Structural Allograft Healing of Critical Sized Femoral Defects in Mice,” Biomaterials 35 (2014): 2752-2759.

[68] Y. Kang, L. Ren, and Y. Yang “Engineering Vascularized Bone Grafts by Integrating a Biomimetic Periosteum and β-TCP Scaffold,” ACS Applied Materials & Interfaces 6 (2014): 9622-9633.

[69] I. Inci, A. Norouz Dizaji, C. Ozel, U. Morali, F. Dogan Guzel, and H. Avci, “Decellularized Inner Body Membranes for Tissue Engineering: A Review,” Journal of Biomaterials Science, Polymer Edition 31 (2020): 1287-1368.

[70] S. F. Evans, H. Chang, and M. L. Knothe Tate, “Elucidating Multiscale Periosteal Mechanobiology: A Key to Unlocking the Smart Properties and Regenerative Capacity of the Periosteum?,” Tissue Engineering Part B: Reviews 19 (2013): 147-159.

[71] X. Shi, S. Chen, Y. Zhao, C. Lai, and H. Wu, “Enhanced Osteogenesis by a Biomimic Pseudo-Periosteum-Involved Tissue Engineering Strategy,” Advanced Healthcare Materials 2, no. 2 (2013): 1229-1235.

[72] P. H. Warnke, T. Douglas, S. Sivananthan, J. Wiltfang, I. Springer, and S. T. Becker, “Tissue Engineering of Periosteal Cell Membranes In Vitro,” Clinical Oral Implants Research 20 (2009): 761-766.

[73] R. Dimitriou, G. I. Mataliotakis, G. M. Calori, and P. V. Giannoudis, “The Role of Barrier Membranes for Guided Bone Regeneration and Restoration of Large Bone Defects: Current Experimental and Clinical Evidence,” BMC Medicine 10 (2012): 1-24.

[74] X. Li, J. Wang, G. Su, et al., “Spatiotemporal Control Over Growth Factor Delivery From Collagen-Based Membrane,” Journal of Biomedical Materials Research Part A 100A (2011): 396-405.

[75] Z. Xu, L. Wu, Y. Tang, et al., “Spatiotemporal Regulation of the Bone Immune Microenvironment via Dam-Like Biphasic Bionic Periosteum for Bone Regeneration,” Advanced Healthcare Materials 12 (2023): 2201661.

[76] K. Yue, G. Trujillo-de Santiago, M. M. Alvarez, A. Tamayol, N. Annabi, and A. Khademhosseini, “Synthesis, Properties, and Biomedical Applications of Gelatin Methacryloyl (GelMA) Hydrogels,” Biomaterials 73 (2015): 254-271.

[77] Q. Xing, K. Yates, C. Vogt, Z. Qian, M. C. Frost, and F. Zhao, “Increasing Mechanical Strength of Gelatin Hydrogels by Divalent Metal Ion Removal,” Scientific Reports 4 (2014): 4706.

[78] Z. Yang, Z. Yang, L. Ding, et al., “Self-Adhesive Hydrogel Biomimetic Periosteum to Promote Critical-Size Bone Defect Repair via Synergistic Osteogenesis and Angiogenesis,” ACS Applied Materials & Interfaces 14 (2022): 36395-36410.

[79] L. Zhang, J. Tang, M. Han, et al., “Effect and Mechanism of a Concentration-Dependent Inorganic Ion Biomimetic Periosteum in a Repairing Bone Defect,” Chemical Engineering Journal 475 (2023): 146046.

[80] W. Liu, W. Bi, Y. Sun, et al., “Biomimetic Organic-Inorganic Hybrid Hydrogel Electrospinning Periosteum for Accelerating Bone Regeneration,” Materials Science and Engineering: C 110 (2020): 110670.

[81] C. Li, W. Zhang, R. Wang, et al., “Nanocomposite Multifunctional Hydrogel for Suppressing Osteosarcoma Recurrence and Enhancing Bone Regeneration,” Chemical Engineering Journal 435 (2022): 134896.

[82] S.-J. Jiang, M.-H. Wang, Z.-Y. Wang, et al., “Radially Porous Nanocomposite Scaffolds With Enhanced Capability for Guiding Bone Regeneration In Vivo,” Advanced Functional Materials 32 (2022): 2110931.

[83] S. H. Teng, E. J. Lee, B. H. Yoon, D. S. Shin, H. E. Kim, and J. S. Oh, “Chitosan/Nanohydroxyapatite Composite Membranes via Dynamic Filtration for Guided Bone Regeneration,” Journal of Biomedical Materials Research Part A 88A (2008): 569-580.

[84] X. Xue, Y. Hu, Y. Deng, and J. Su, “Recent Advances in Design of Functional Biocompatible Hydrogels for Bone Tissue Engineering,” Advanced Functional Materials 31 (2021): 2009432.

[85] S. Bhushan, S. Singh, T. K. Maiti, et al., “Cerium Oxide Nanoparticles Disseminated Chitosan Gelatin Scaffold for Bone Tissue Engineering Applications,” International Journal of Biological Macromolecules 236 (2023): 123813.

[86] R. F. Bombaldi de Souza, F. C. Bombaldi de Souza, A. Thorpe, D. Mantovani, K. C. Popat, and Â. M. Moraes, “Phosphorylation of Chitosan to Improve Osteoinduction of Chitosan/Xanthan-Based Scaffolds for Periosteal Tissue Engineering,” International Journal of Biological Macromolecules 143 (2020): 619-632.

[87] H. Guo, X. Li, X. Yuan, and X. Ma, “Reconstruction of Radial Bone Defects Using the Reinforced Tissue-Engineered Periosteum,” Journal of Trauma and Acute Care Surgery 72 (2012): E94-E100.

[88] R. Romero, J. K. Travers, E. Asbury, et al., “Combined Delivery of FGF-2, TGF-β1, and Adipose-Derived Stem Cells From an Engineered Periosteum to a Critical-Sized Mouse Femur Defect,” Journal of Biomedical Materials Research Part A 105 (2016): 900-911.

[89] C. Li, W. Zhang, Y. Nie, et al., “Integrated and Bifunctional Bilayer 3D Printing Scaffold for Osteochondral Defect Repair,” Advanced Functional Materials 33 (2023): 2214158.

[90] J. Long, Z. Yao, W. Zhang, et al., “Regulation of Osteoimmune Microenvironment and Osteogenesis by 3D-Printed PLAG/Black Phosphorus Scaffolds for Bone Regeneration,” Advanced Science 10 (2023): 2302539.

[91] J. Xue, M. He, Y. Liang, et al., “Fabrication and Evaluation Of Electrospun PCL-Gelatin Micro-/Nanofiber Membranes for Anti-Infective GTR Implants,” Journal of Materials Chemistry B 2 (2014): 6867-6877.

[92] L. Wu, Y. Gu, L. Liu, et al., “Hierarchical Micro/Nanofibrous Membranes of Sustained Releasing VEGF for Periosteal Regeneration,” Biomaterials 227 (2020): 119555.

[93] M. Kharaziha, M. H. Fathi, and H. Edris, “Development of Novel Aligned Nanofibrous Composite Membranes for Guided Bone Regeneration,” Journal of the Mechanical Behavior of Biomedical Materials 24 (2013): 9-20.

[94] Q. Zhang, K. Huang, J. Tan, et al., “Metal-Phenolic Networks Modified Polyurethane as Periosteum for Bone Regeneration,” Chinese Chemical Letters 33 (2022): 1623-1626.

[95] F. Sun, J. Chen, S. Jin, et al., “Development of Biomimetic Trilayer Fibrous Membranes for Guided Bone Regeneration,” Journal of Materials Chemistry B 7 (2019): 665-675.

[96] Y. Li, M. D. Hoffman, and D. S. W. Benoit, “Matrix Metalloproteinase (MMP)-Degradable Tissue Engineered Periosteum Coordinates Allograft Healing via Early Stage Recruitment and Support of Host Neurovasculature,” Biomaterials 268 (2021): 120535.

[97] Y. Bian, T. Hu, Z. Lv, et al., “Bone Tissue Engineering for Treating Osteonecrosis of the Femoral Head,” Exploration 3 (2023): 20210105.

[98] N. Ardjomandi, A. Henrich, J. Huth, et al., “Coating of ß-Tricalcium Phosphate Scaffolds—A Comparison Between Graphene Oxide and Poly-Lactic-co-Glycolic Acid,” Biomedical Materials 10 (2015): 045018.

[99] X. He, W. Liu, Y. Liu, et al., “Nano Artificial Periosteum PLGA/MgO/Quercetin Accelerates Repair of Bone Defects Through Promoting Osteogenic − Angiogenic Coupling Effect via Wnt/ β-Catenin Pathway,” Materials Today Bio 16 (2022): 100348.

[100] T. Wang, Y. Zhai, M. Nuzzo, X. Yang, Y. Yang, and X. Zhang, “Layer-By-Layer Nanofiber-Enabled Engineering of Biomimetic Periosteum for Bone Repair and Reconstruction,” Biomaterials 182 (2018): 279-288.

[101] S. Türkkan, A. E. Pazarçeviren, D. Keskin, N. E. Machin, Ö. Duygulu, and A. Tezcaner, “Nanosized CaP-Silk Fibroin-PCL-PEG-PCL/PCL Based Bilayer Membranes for Guided Bone Regeneration,” Materials Science and Engineering: C 80 (2017): 484-493.

[102] Y. M. Yousry, V. K. Wong, R. Ji, et al., “Shear Mode Ultrasonic Transducers From Flexible Piezoelectric PLLA Fibers for Structural Health Monitoring,” Advanced Functional Materials 33 (2023): 2213582.

[103] C. Shuai, W. Yang, P. Feng, S. Peng, and H. Pan, “Accelerated Degradation of HAP/PLLA Bone Scaffold by PGA Blending Facilitates Bioactivity and Osteoconductivity,” Bioactive Materials 6 (2021): 490-502.

[104] P. Feng, P. Wu, C. Gao, et al., “A Multimaterial Scaffold With Tunable Properties: Toward Bone Tissue Repair,” Advanced Science 5 (2018): 1700817.

[105] K. Liu, L. Li, J. Chen, et al., “Bone ECM-Like 3D Printing Scaffold With Liquid Crystalline and Viscoelastic Microenvironment for Bone Regeneration,” ACS Nano 16 (2022): 21020-21035.

[106] X. Hua, M. Hou, L. Deng, et al., “Irisin-Loaded Electrospun Core-Shell Nanofibers as Calvarial Periosteum Accelerate Vascularized Bone Regeneration by Activating the Mitochondrial SIRT3 Pathway,” Regenerative Biomaterials 11 (2023): rbad096.

[107] M. Vukomanović, L. Gazvoda, M. Kurtjak, et al., “Filler-Enhanced Piezoelectricity of Poly-L-Lactide and Its Use as a Functional Ultrasound-Activated Biomaterial,” Small 19 (2023): 2301981.

[108] H. H. Jiang, X. J. Song, H. P. Lv, X. G. Chen, R. G. Xiong, and H. Y. Zhang, “Observation of Ferroelectric Lithography on Biodegradable PLA Films,” Advanced Materials 36 (2023): 2307936.

[109] Y. Liu, G. Dzidotor, T. T. Le, et al., “Exercise-Induced Piezoelectric Stimulation for Cartilage Regeneration in Rabbits,” Science Translational Medicine 14 (2022): eabi7282.

[110] T. Zheng, H. Zhao, Y. Huang, et al., “Piezoelectric Calcium/Manganese-Doped Barium Titanate Nanofibers With Improved Osteogenic Activity,” Ceramics International 47 (2021): 28778-28789.

[111] Y. Lai, Y. Li, H. Cao, et al., “Osteogenic Magnesium Incorporated Into PLGA/TCP Porous Scaffold by 3D Printing for Repairing Challenging Bone Defect,” Biomaterials 197 (2019): 207-219.

[112] C. Li, W. Zhang, Y. Nie, et al., “Time-Sequential and Multi-Functional 3D Printed MgO₂/PLGA Scaffold Developed as a Novel Biodegradable and Bioactive Bone Substitute for Challenging Postsurgical Osteosarcoma Treatment,” Advanced Materials 36 (2023): 2308875. https://doi.org/10.1002/adma.202308875.

[113] R. Zhang, S. Han, L. Liang, et al., “Ultrasonic-Driven Electrical Signal-Iron Ion Synergistic Stimulation Based on Piezotronics Induced Neural Differentiation of Mesenchymal Stem Cells on FeOOH/PVDF Nanofibrous Hybrid Membrane,” Nano Energy 87 (2021): 106192.

[114] X. Ma, S. Li, S. Dong, et al., “Regulating the Output Performance of Triboelectric Nanogenerator by Using P(VDF-TrFE) Langmuir Monolayers,” Nano Energy 66 (2019): 104090.

[115] C. Liu, Y. Lou, Z. Sun, et al., “4D Printing of Personalized-Tunable Biomimetic Periosteum With Anisotropic Microstructure for Accelerated Vascularization and Bone Healing,” Advanced Healthcare Materials 12 (2023): 2202868.

[116] X. Zhang, X. Cui, D. Wang, et al., “Piezoelectric Nanotopography Induced Neuron-Like Differentiation of Stem Cells,” Advanced Functional Materials 29 (2019): 1900372.

[117] G. S. Hussey, J. L. Dziki, and S. F. Badylak, “Extracellular Matrix-Based Materials for Regenerative Medicine,” Nature Reviews Materials 3 (2018): 159-173.

[118] D. Beniker, D. McQuillan, S. Livesey, et al., “The Use of Acellular Dermal Matrix as a Scaffold for Periosteum Replacement,” Orthopedics 26 (2003): S591-S596.

[119] F. Guilak, L. G. Alexopoulos, M. A. Haider, H. P. Ting-Beall, and L. A. Setton, “Zonal Uniformity in Mechanical Properties of the Chondrocyte Pericellular Matrix: Micropipette Aspiration of Canine Chondrons Isolated by Cartilage Homogenization,” Annals of Biomedical Engineering 33 (2005): 1312-1318.

[120] D. Zhang, P. Gao, Q. Li, et al., “Engineering Biomimetic Periosteum with β-TCP Scaffolds to Promote Bone Formation in Calvarial Defects of Rats,” Stem Cell Research & Therapy 8 (2017): 1-11.

[121] R. Romero, L. Chubb, J. K. Travers, T. R. Gonzales, N. P. Ehrhart, and M. J. Kipper, “Coating Cortical Bone Allografts With Periosteum-Mimetic Scaffolds Made of Chitosan, Trimethyl Chitosan, and Heparin,” Carbohydrate Polymers 122 (2015): 144-151.

[122] S. G. Caridade, C. Monge, J. Almodóvar, et al., “Myoconductive and Osteoinductive Free-Standing Polysaccharide Membranes,” Acta Biomaterialia 15 (2015): 139-149.

[123] N. L. D'Elía, R. Rial Silva, J. Sartuqui, et al., “Development and Characterisation of Bilayered Periosteum-Inspired Composite Membranes Based on Sodium Alginate-Hydroxyapatite Nanoparticles,” Journal of Colloid and Interface Science 572 (2020): 408-420.

[124] M. M. Stevens, H. F. Qanadilo, R. Langer, and V. P. Shastri, “A Rapid-Curing Alginate Gel System: Utility in Periosteum-Derived Cartilage Tissue Engineering,” Biomaterials 25 (2004): 887-894.

[125] J. Kim, W.-G. Bae, H.-W. Choung, et al., “Multiscale Patterned Transplantable Stem Cell Patches for Bone Tissue Regeneration,” Biomaterials 35 (2014): 9058-9067.

[126] Z. Tu, F. Han, Z. Zhu, et al., “Sustained Release of Basic Fibroblast Growth Factor in Micro/Nanofibrous Scaffolds Promotes Annulus Fibrosus Regeneration,” Acta Biomaterialia 166 (2023): 241-253.

[127] M. Gong, C. Chi, J. Ye, et al., “Icariin-Loaded Electrospun PCL/Gelatin Nanofiber Membrane as Potential Artificial Periosteum,” Colloids and Surfaces B: Biointerfaces 170 (2018): 201-209.

[128] M. D. Hoffman, C. Xie, X. Zhang, and D. S. W. Benoit, “The Effect of Mesenchymal Stem Cells Delivered via Hydrogel-Based Tissue Engineered Periosteum on Bone Allograft Healing,” Biomaterials 34 (2013): 8887-8898.

[129] M. D. Hoffman and D. S. W. Benoit, “Emulating Native Periosteum Cell Population and Subsequent Paracrine Factor Production to Promote Tissue Engineered Periosteum-Mediated Allograft Healing,” Biomaterials 52 (2015): 426-440.

[130] Y. Sun, Z. Gao, X. Zhang, et al., “3D-Printed, Bi-Layer, Biomimetic Artificial Periosteum for Boosting Bone Regeneration,” Bio-Design and Manufacturing 5 (2022): 540-555.

[131] D. You, G. Chen, C. Liu, et al., “4D Printing of Multi-Responsive Membrane for Accelerated In Vivo Bone Healing Via Remote Regulation of Stem Cell Fate,” Advanced Functional Materials 31 (2021): 2103920.

[132] Y. Du, L. Xing, P. Hou, et al., “Dual Stimulus Response Mechanical Properties Tunable Biodegradable and Biocompatible PLCL/PPDO Based Shape Memory Composites,” Colloids and Surfaces A: Physicochemical and Engineering Aspects 648 (2022): 129244.

[133] H. Zhang, H. Huang, G. Hao, et al., “3D Printing Hydrogel Scaffolds With Nanohydroxyapatite Gradient to Effectively Repair Osteochondral Defects in Rats,” Advanced Functional Materials 31 (2021): 2006697.

[134] I. Ullah, Z. Hussain, Y. Zhang, et al., “Inorganic Nanomaterial-Reinforced Hydrogel Membrane as an Artificial Periosteum,” Applied Materials Today 28 (2022): 101532.

[135] J. Chen, J. Chen, Z. Zhu, et al., “Drug-Loaded and Anisotropic Wood-Derived Hydrogel Periosteum with Super Antibacterial, Anti-Inflammatory, and Osteogenic Activities,” ACS Applied Materials & Interfaces 14 (2022): 50485-50498.

[136] Y. Zhang, C. Li, A. Guo, et al., “Black Phosphorus Boosts Wet-Tissue Adhesion of Composite Patches by Enhancing Water Absorption and Mechanical Properties,” Nature Communication 15 (2024): 1618.

[137] X. Gao, Q. Wang, L. Ren, et al., “Metal-Phenolic Networks as a Novel Filler to Advance Multi-Functional Immunomodulatory Biocomposites,” Chemical Engineering Journal 426 (2021): 131825.

[138] F. Wang, D. Xia, S. Wang, et al., “Photocrosslinkable Col/PCL/Mg Composite Membrane Providing Spatiotemporal Maintenance and Positive Osteogenetic Effects During Guided Bone Regeneration,” Bioactive Materials 13 (2022): 53-63.

[139] A. Sydney Gladman, E. A. Matsumoto, R. G. Nuzzo, L. Mahadevan, and J. A. Lewis, “Biomimetic 4D Printing,” Nature Materials 15 (2016): 413-418.

[140] H. Sun, Y. Shang, J. Guo, et al., “Artificial Periosteum with Oriented Surface Nanotopography and High Tissue Adherent Property,” ACS Applied Materials & Interfaces 15 (2023): 45549-45560.

[141] Z. Lu, W. Wang, J. Zhang, P. Bártolo, H. Gong, and J. Li, “Electrospun Highly Porous Poly(L-Lactic Acid)-Dopamine-SiO₂ Fibrous Membrane for Bone Regeneration,” Materials Science and Engineering: C 117 (2020): 111359.

[142] F. Zhao, S. Hu, F. Wang, and L. Wang, “A Sulfonated PEEK/PCL Composite Nanofibrous Membrane for Periosteum Tissue Engineering Application,” Journal of Materials Science 54 (2019): 12012-12023.

[143] Z. He, C. Sun, Y. Ma, et al., “Rejuvenating Aged Bone Repair Through Multihierarchy Reactive Oxygen Species-Regulated Hydrogel,” Advanced Materials 36 (2024): 2306552.

[144] G. Zhu, T. Zhang, M. Chen, et al., “Bone Physiological Microenvironment and Healing Mechanism: Basis for Future Bone-Tissue Engineering Scaffolds,” Bioactive Materials 6 (2021): 4110-4140.

[145] B. W. M. de Wildt, R. van der Meijden, P. A. A. Bartels, et al., “Bioinspired Silk Fibroin Mineralization for Advanced In Vitro Bone Remodeling Models,” Advanced Functional Materials 32 (2022): 2206992.

[146] Y. Shuai, H. Lu, R. Lv, et al., “Biomineralization Directed by Prenucleated Calcium and Phosphorus Nanoclusters Improving Mechanical Properties and Osteogenic Potential of Antheraea Pernyi Silk Fibroin-Based Artificial Periosteum,” Advanced Healthcare Materials 10 (2021): 2001695.

[147] D. Qin, X. You, H. Wang, et al., “Natural Micropatterned Fish Scales Combing Direct Osteogenesis and Osteoimmunomodulatory Functions for Enhancing Bone Regeneration,” Composites Part B: Engineering 255 (2023): 110620.

[148] Y. Wei, M. Ju, F. Zheng, et al., “Cuttlebone-Derived Organic Matrix: A Facile Periosteum Substitute for Bone Regeneration,” Advanced Functional Materials 33 (2023): 2214095.

[149] C. S. Kim, J. H. Kim, B. Kim, et al., “A Specific Groove Pattern Can Effectively Induce Osteoblast Differentiation,” Advanced Functional Materials 27 (2017): 1703569.

[150] Y. Yang, T. Xu, H. P. Bei, Y. Zhao, and X. Zhao, “Sculpting Bio-Inspired Surface Textures: An Adhesive Janus Periosteum,” Advanced Functional Materials 31 (2021): 2104636.

[151] G. Yang, H. Liu, Y. Cui, et al., “Bioinspired Membrane Provides Periosteum-Mimetic Microenvironment for Accelerating Vascularized Bone Regeneration,” Biomaterials 268 (2021): 120561.

[152] S. Lv, X. Yuan, J. Xiao, and X. Jiang, “Hemostasis-Osteogenesis Integrated Janus Carboxymethyl Chitin/Hydroxyapatite Porous Membrane for Bone Defect Repair,” Carbohydrate Polymers 313 (2023): 120888.

[153] X. Li, S. Yang, S. Wang, et al., “A Hierarchical Biomimetic Periosteum Combined Immunomodulatory and Osteogenic Functions for Bone Regeneration,” Composites Part B: Engineering 243 (2022): 110099.

[154] K.-R. Zhang, H.-L. Gao, X.-F. Pan, et al., “Multifunctional Bilayer Nanocomposite Guided Bone Regeneration Membrane,” Matter 1 (2019): 770-781.

[155] Q. Wang, Y. Feng, M. He, W. Zhao, L. Qiu, and C. Zhao, “A Hierarchical Janus Nanofibrous Membrane Combining Direct Osteogenesis and Osteoimmunomodulatory Functions for Advanced Bone Regeneration,” Advanced Functional Materials 31 (2021): 2008906.

[156] G. Cheng, J. Chen, Q. Wang, et al., “Promoting Osteogenic Differentiation in Pre-Osteoblasts and Reducing Tibial Fracture Healing Time Using Functional Nanofibers,” Nano Research 11 (2018): 3658-3677.

[157] L. Laijun, Z. Yu, L. Chaojing, M. Jifu, W. Fujun, and W. Lu, “An Enhanced Periosteum Structure/Function Dual Mimicking Membrane for In-Situ Restorations of Periosteum and Bone,” Biofabrication 13 (2021): 035041.

[158] F. Tao, Y. Cheng, H. Tao, et al., “Carboxymethyl Chitosan/Sodium Alginate-Based Micron-Fibers Fabricated by Emulsion Electrospinning for Periosteal Tissue Engineering,” Materials & Design 194 (2020): 108849.

[159] A. Haumer, P. E. Bourgine, P. Occhetta, G. Born, R. Tasso, and I. Martin, “Delivery of Cellular Factors to Regulate Bone Healing,” Advanced Drug Delivery Reviews 129 (2018): 285-294.

[160] H. Liu, Y. Shi, Y. Zhu, et al., “Bioinspired Piezoelectric Periosteum to Augment Bone Regeneration via Synergistic Immunomodulation and Osteogenesis,” ACS Applied Materials and Interfaces 15 (2023): 12273-12293.

[161] K. Dai, S. Deng, Y. Yu, F. Zhu, J. Wang, and C. Liu, “Construction of Developmentally Inspired Periosteum-Like Tissue for Bone Regeneration,” Bone Research 10 (2022): 1.

[162] H. Sun, J. Dong, Y. Wang, et al., “Polydopamine-Coated Poly(L-Lactide) Nanofibers with Controlled Release of VEGF and BMP-2 as a Regenerative Periosteum,” ACS Biomaterials Science & Engineering 7 (2021): 4883-4897.

[163] Y. Zhu, J. Zhou, B. Dai, et al., “A Bilayer Membrane Doped With Struvite Nanowires for Guided Bone Regeneration,” Advanced Healthcare Materials 11 (2022): 2201679.

[164] Q.-Q. Wan, K. Jiao, Y.-X. Ma, et al., “Smart, Biomimetic Periosteum Created From the Cerium(III, IV) Oxide-Mineralized Eggshell Membrane,” ACS Applied Materials & Interfaces 14 (2022): 14103-14119.

[165] H. Wu, S. Shi, H. Zhou, et al., “Stem Cell Self-Triggered Regulation and Differentiation on Polyvinylidene Fluoride Electrospun Nanofibers,” Advanced Functional Materials 34 (2023): 2309270.

[166] C. Yu, X. Ying, M.-A. Shahbazi, et al., “A Nano-Conductive Osteogenic Hydrogel to Locally Promote Calcium Influx for Electro-Inspired Bone Defect Regeneration,” Biomaterials 301 (2023): 122266.

[167] Q. Li, W. Liu, W. Hou, et al., “Micropatterned Photothermal Double-Layer Periosteum With Angiogenesis-Neurogenesis Coupling Effect for Bone Regeneration,” Materials Today Bio 18 (2023): 100536.

[168] K. A. Alexander, L.-J. Raggatt, S. Millard, et al., “Resting and Injury-Induced Inflamed Periosteum Contain Multiple Macrophage Subsets that are Located at Sites of Bone Growth and Regeneration,” Immunology and Cell Biology 95 (2017): 7-16.

[169] F. Loi, L. A. Córdova, J. Pajarinen, T.-h. Lin, Z. Yao, and S. B. Goodman, “Inflammation, Fracture and Bone Repair,” Bone 86 (2016): 119-130.

[170] Y.-H. Kim, R. O. C. Oreffo, and J. I. Dawson, “From Hurdle to Springboard: The Macrophage as Target in Biomaterial-Based Bone Regeneration Strategies,” Bone 159 (2022): 116389.

[171] K. L. Spiller, R. R. Anfang, K. J. Spiller, et al., “The Role of Macrophage Phenotype in Vascularization of Tissue Engineering Scaffolds,” Biomaterials 35 (2014): 4477-4488.

[172] Y. Zhang, T. Böse, R. E. Unger, J. A. Jansen, C. J. Kirkpatrick, and J. J. J. P. van den Beucken, “Macrophage Type Modulates Osteogenic Differentiation of Adipose Tissue MSCs,” Cell and Tissue Research 369 (2017): 273-286.

[173] J. Lee, H. Byun, S. K. Madhurakkat Perikamana, S. Lee, and H. Shin, “Current Advances in Immunomodulatory Biomaterials for Bone Regeneration,” Advanced Healthcare Materials 8 (2018): 1801106.

[174] Y. Qiao, L. Yu, P. Yang, et al., “Spatiotemporal Immunomodulation and Biphasic Osteo-Vascular Aligned Electrospun Membrane for Diabetic Periosteum Regeneration,” Advanced Science 10 (2023): 2302874.

[175] M. F. Pittenger, A. M. Mackay, S. C. Beck, et al., “Multilineage Potential of Adult Human Mesenchymal Stem Cells,” Science 284 (1999): 143-147.

[176] W.-T. Su, W.-L. Chiou, H.-H. Yu, and T.-Y. Huang, “Differentiation Potential of SHEDs Using Biomimetic Periosteum Containing Dexamethasone,” Materials Science and Engineering: C 58 (2016): 1036-1045.

[177] J. A. Burdick and K. S. Anseth, “Photoencapsulation of Osteoblasts in Injectable RGD-Modified PEG Hydrogels for Bone Tissue Engineering,” Biomaterials 23 (2002): 4315-4323.

[178] C. Chu, J. Deng, Y. Hou, et al., “Application of PEG and EGCG Modified Collagen-Base Membrane to Promote Osteoblasts Proliferation,” Materials Science and Engineering: C 76 (2017): 31-36.

[179] Y.-C. Chou, Y.-S. Cheng, Y.-H. Hsu, Y.-H. Yu, and S.-J. Liu, “A Bio-Artificial Poly([D,L]-Lactide-co-Glycolide) Drug-Eluting Nanofibrous Periosteum for Segmental Long Bone Open Fractures With Significant Periosteal Stripping Injuries,” International Journal of Nanomedicine 11 (2016): 941-953.

[180] K. D. Hankenson, K. Gagne, and M. Shaughnessy, “Extracellular Signaling Molecules to Promote Fracture Healing and Bone Regeneration,” Advanced Drug Delivery Reviews 94 (2015): 3-12.

[181] K. N. Malizos and L. K. Papatheodorou, “The Healing Potential of the Periosteum,” Injury 36 (2005): S13-S19.

[182] D. W. Hutmacher and M. Sittinger, “Periosteal Cells in Bone Tissue Engineering,” Tissue Engineering 9 (2003): 45-64.

[183] M. Gnecchi, Z. Zhang, A. Ni, and V. J. Dzau, “Paracrine Mechanisms in Adult Stem Cell Signaling and Therapy,” Circulation Research 103 (2008): 1204-1219.

[184] L. Chen, E. E. Tredget, P. Y. G. Wu, and Y. Wu, “Paracrine Factors of Mesenchymal Stem Cells Recruit Macrophages and Endothelial Lineage Cells and Enhance Wound Healing,”PLoS ONE 3 (2008): e1886.

[185] K. Hu and B. R. Olsen, “The Roles of Vascular Endothelial Growth Factor in Bone Repair and Regeneration,” Bone 91 (2016): 30-38.

[186] R. Bielby, E. Jones, and D. McGonagle, “The Role of Mesenchymal Stem Cells in Maintenance and Repair of Bone,” Injury 38 (2007): S26-S32.

[187] V. Chappuis, L. Gamer, K. Cox, J. W. Lowery, D. D. Bosshardt, and V. Rosen, “Periosteal BMP2 Activity Drives Bone Graft Healing,” Bone 51 (2012): 800-809.

[188] P. Kraj, “Bone Morphogenic Protein Signaling and Melanoma,” Current Treatment Options in Oncology 22 (2021): 48.

[189] T. Mattar, P. F. Friedrich, and A. T. Bishop, “Effect of rhBMP-2 and VEGF in a Vascularized Bone Allotransplant Experimental Model Based on Surgical Neoangiogenesis,” Journal of Orthopaedic Research 31 (2012): 561-566.

[190] M. M. L. Deckers, R. L. van Bezooijen, G. van der Horst, et al., “Bone Morphogenetic Proteins Stimulate Angiogenesis Through Osteoblast-Derived Vascular Endothelial Growth Factor A,” Endocrinology 143 (2002): 1545-1553.

[191] D. H. R. Kempen, L. B. Creemers, J. Alblas, et al., “Growth Factor Interactions in Bone Regeneration,” Tissue Engineering Part B: Reviews 16 (2010): 551-566.

[192] M. P. G. Bostrom, J. M. Lane, W. S. Berberian, et al., “Immunolocalization and Expression of Bone Morphogenetic Proteins 2 and 4 in Fracture Healing,” Journal of Orthopaedic Research 13 (2005): 357-367.

[193] K. Hanada, L. A. Solchaga, A. I. Caplan, et al., “BMP-2 Induction and TGF-beta 1 Modulation of Rat Periosteal Cell Chondrogenesis,” Journal of Cellular Biochemistry 81 (2001): 284-294.

[194] J. Fiedler, F. Leucht, J. Waltenberger, C. Dehio, and R. E. Brenner, “VEGF-A and PlGF-1 Stimulate Chemotactic Migration of Human Mesenchymal Progenitor Cells,” Biochemical and Biophysical Research Communications 334 (2005): 561-568.

[195] F. Granero-Moltó, J. A. Weis, M. I. Miga, et al., “Regenerative Effects of Transplanted Mesenchymal Stem Cells in Fracture Healing,” Stem Cells 27 (2009): 1887-1898.

[196] C. Wang, W. Huang, Y. Zhou, et al., “3D Printing of Bone Tissue Engineering Scaffolds,” Bioactive Materials 5 (2020): 82-91.

[197] C. Chen, F. Liu, Y. Tang, et al., “Cell-Loading Capability and Chondrogenic Inducibility for Tissue-Engineered Fibrocartilage and Bone-Tendon Healing,” ACS Applied Materials & Interfaces 11 (2019): 2891-2907.

[198] H. Li, H. Wang, J. Pan, et al. ACS Applied Materials & Interfaces, “Nanoscaled Bionic Periosteum Orchestrating the Osteogenic Microenvironment for Sequential Bone Regeneration,”12 (2020): 36823-36836.

[199] Y. Zhang, C. Li, W. Zhang, et al., “3D-Printed NIR-Responsive Shape Memory Polyurethane/Magnesium Scaffolds With Tight-Contact for Robust Bone Regeneration,” Bioactive Materials 16 (2022): 218-231.

[200] J. Li, A. Kreicbergs, J. Bergström, A. Stark, and M. Ahmed, “Site-Specific CGRP Innervation Coincides With Bone Formation During Fracture Healing and Modeling: A Study in Rat Angulated Tibia,” Journal of Orthopaedic Research 25 (2007): 1204-1212.

[201] L. Wang, Y. Pang, Y. Tang, et al., “A Biomimetic Piezoelectric Scaffold With Sustained Mg2+ Release Promotes Neurogenic and Angiogenic Differentiation for Enhanced Bone Regeneration,” Bioactive Materials 25 (2023): 399-414.

[202] H. D. Kim, H. L. Jang, H.-Y. Ahn, et al., “Biomimetic Whitlockite Inorganic Nanoparticles-Mediated In Situ Remodeling and Rapid Bone Regeneration,” Biomaterials 112 (2017): 31-43.

[203] H. L. Jang, K. Jin, J. Lee, et al., “Revisiting Whitlockite, the Second Most Abundant Biomineral in Bone: Nanocrystal Synthesis in Physiologically Relevant Conditions and Biocompatibility Evaluation,” ACS Nano 8 (2014): 634-641.

[204] J. Mi, J. Xu, H. Yao, et al., “Calcitonin Gene-Related Peptide Enhances Distraction Osteogenesis by Increasing Angiogenesis,” Tissue Engineering Part A 27 (2021): 87-102.

[205] L. Sun, M. Wang, S. Chen, et al., “Molecularly Engineered Metal-Based Bioactive Soft Materials—Neuroactive Magnesium Ion/Polymer Hybrids,” Acta Biomaterialia 85 (2019): 310-319.

[206] X. Li, B. Dai, J. Guo, et al., “Biosynthesized Bandages Carrying Magnesium Oxide Nanoparticles Induce Cortical Bone Formation by Modulating Endogenous Periosteal Cells,” ACS Nano 16 (2022): 18071-18089.

[207] J.-W. Park, K.-B. Park, and J.-Y. Suh, “Effects of Calcium Ion Incorporation on Bone Healing of Ti6Al4V Alloy Implants in Rabbit Tibiae,” Biomaterials 28 (2007): 3306-3313.

[208] A. Aguirre, A. González, J. A. Planell, and E. Engel, “Extracellular Calcium Modulates In Vitro Bone Marrow-Derived Flk-1+ CD34+ Progenitor Cell Chemotaxis and Differentiation Through a Calcium-Sensing Receptor,” Biochemical and Biophysical Research Communications 393 (2010): 156-161.

[209] W. Nie, C. Peng, X. Zhou, et al., “Three-Dimensional Porous Scaffold by Self-Assembly of Reduced Graphene Oxide and Nano-Hydroxyapatite Composites for Bone Tissue Engineering,” Carbon 116 (2017): 325-337.

[210] X. Han, M. Sun, B. Chen, et al., “Lotus Seedpod-Inspired Internal Vascularized 3D Printed Scaffold for Bone Tissue Repair,” Bioactive Materials 6 (2021): 1639-1652.

[211] H. Liu, W. Wen, S. Chen, C. Zhou, and B. Luo, “Preparation of Icariin and Deferoxamine Functionalized Poly(L-lactide)/Chitosan Micro/Nanofibrous Membranes With Synergistic Enhanced Osteogenesis and Angiogenesis,” ACS Applied Bio Materials 1 (2018): 389-402.

[212] Q. Ran, Y. Yu, W. Chen, et al., “Deferoxamine Loaded Titania Nanotubes Substrates Regulate Osteogenic and Angiogenic Differentiation of MSCs via Activation of HIF-1α Signaling,” Materials Science and Engineering: C 91 (2018): 44-54.

[213] X. He, W. Li, K. Liu, et al., “Anisotropic and Robust Hydrogels Combined Osteogenic and Angiogenic Activity as Artificial Periosteum,” Composites Part B: Engineering 233 (2022): 109627.

[214] Y. Liu, X. Zhang, C. Cao, et al., “Built-In Electric Fields Dramatically Induce Enhancement of Osseointegration,” Advanced Functional Materials 27 (2017): 1703771.

[215] H. Wu, H. Dong, Z. Tang, et al., “Electrical Stimulation of Piezoelectric BaTiO₃ Coated Ti6Al4V Scaffolds Promotes Anti-Inflammatory Polarization of Macrophages and Bone Repair via MAPK/JNK Inhibition and OXPHOS Activation,” Biomaterials 293 (2023): 121990.

[216] Y. Xiong, B.-B. Mi, Z. Lin, et al., “The Role of the Immune Microenvironment in Bone, Cartilage, and Soft Tissue Regeneration: From Mechanism to Therapeutic Opportunity,” Military Medical Research 9 (2022): 65.

[217] Y. Kong, F. Liu, B. Ma, et al., “Wireless Localized Electrical Stimulation Generated by an Ultrasound-Driven Piezoelectric Discharge Regulates Proinflammatory Macrophage Polarization,” Advanced Science 8 (2021): 2100962.

[218] Y. Du, J. L. Guo, J. Wang, A. G. Mikos, and S. Zhang, “Hierarchically Designed Bone Scaffolds: From Internal Cues to External Stimuli,” Biomaterials 218 (2019): 119334.

[219] B. Tandon, J. J. Blaker, and S. H. Cartmell, “Piezoelectric Materials as Stimulatory Biomedical Materials and Scaffolds for Bone Repair,” Acta Biomaterialia 73 (2018): 1-20.

[220] Z. Wei, F. Jin, T. Li, et al., “Physical Cue-Based Strategies on Peripheral Nerve Regeneration,” Advanced Functional Materials 33 (2023): 2209658.

[221] C. Goldstein, S. Sprague, and B. A. Petrisor, “Electrical Stimulation for Fracture Healing: Current Evidence,” Journal of Orthopaedic Trauma 24 (2010): S62-S65.

[222] X. Dai, B. C. Heng, Y. Bai, et al., “Restoration of Electrical Microenvironment Enhances Bone Regeneration Under Diabetic Conditions by Modulating Macrophage Polarization,” Bioactive Materials 6 (2021): 2029-2038.

[223] A. H. Rajabi, M. Jaffe, and T. L. Arinzeh, “Piezoelectric Materials for Tissue Regeneration: A Review,” Acta Biomaterialia 24 (2015): 12-23.

[224] T. Wang, W. Li, Y. Zhang, et al., “Bioprinted Constructs That Simulate Nerve-Bone Crosstalk to Improve Microenvironment for Bone Repair,” Bioactive Materials 27 (2023): 377-393.

[225] Y. Su, L. Zeng, R. Deng, et al., “Endogenous Electric Field-Coupled PD@BP Biomimetic Periosteum Promotes Bone Regeneration Through Sensory Nerve via Fanconi Anemia Signaling Pathway,” Advanced Healthcare Materials 12 (2023): 2203027.

[226] G. Li, T. Zheng, L. Wu, et al., “Bionic Microenvironment-Inspired Synergistic Effect of Anisotropic Micro-Nanocomposite Topology and Biology Cues on Peripheral Nerve Regeneration,” Science Advances 7: eabi5812.

[227] Z. Hao, L. Ren, Z. Zhang, et al., “A Multifunctional Neuromodulation Platform Utilizing Schwann Cell-Derived Exosomes Orchestrates Bone Microenvironment via Immunomodulation, Angiogenesis and Osteogenesis,” Bioactive Materials 23 (2023): 206-222.

[228] I. Rajpar and R. E. Tomlinson, “Function of Peripheral Nerves in the Development and Healing of Tendon and Bone,” Seminars in Cell and Developmental Biology 123 (2022): 48-56.

[229] Q. Q. Wan, W. P. Qin, M. J. Shen, et al., “Simultaneous Regeneration of Bone and Nerves Through Materials and Architectural Design: Are We There Yet?,” Advanced Functional Materials 30 (2020): 2003542.

[230] Q. Q. Wan, W. P. Qin, Y. X. Ma, et al., “Crosstalk Between Bone and Nerves Within Bone,” Advanced Science 8 (2021): 2003390.

[231] Y. Su, Q. Gao, R. Deng, et al., “Aptamer Engineering Exosomes Loaded on Biomimetic Periosteum to Promote Angiogenesis and Bone Regeneration by Targeting Injured Nerves via JNK3 MAPK Pathway,” Materials Today Bio 16 (2022): 100434.

[232] G. Li, S. Li, L. Zhang, et al. “Construction of Biofunctionalized Anisotropic Hydrogel Micropatterns and Their Effect on Schwann Cell Behavior in Peripheral Nerve Regeneration,” ACS Applied Materials & Interfaces 11 (2019): 37397-37410.

[233] G. Li, X. Zhao, W. Zhao, et al., “Porous Chitosan Scaffolds With Surface Micropatterning and Inner Porosity and Their Effects on Schwann Cells,” Biomaterials 35 (2014): 8503-8513.

[234] S. Sun, N. H. Diggins, Z. J. Gunderson, J. C. Fehrenbacher, F. A. White, and M. A. Kacena, “No Pain, No Gain? The Effects of Pain-Promoting Neuropeptides and Neurotrophins on Fracture Healing,” Bone 131 (2020): 115109.

[235] H. Zhang, M. Zhang, D. Zhai, et al., “Polyhedron-Like Biomaterials for Innervated and Vascularized Bone Regeneration,” Advanced Materials 35 (2023): 2302716.

[236] H. Zhang, C. Qin, M. Zhang, et al., “Calcium Silicate Nanowires-Containing Multicellular Bioinks for 3D Bioprinting of Neural-Bone Constructs,” Nano Today 46 (2022): 101584.

[237] S. Lee, C. Hwang, S. Marini, et al., “NGF-TrkA Signaling Dictates Neural Ingrowth and Aberrant Osteochondral Differentiation After Soft Tissue Trauma,” Nature Communications 12 (2021): 4939.

[238] Z. Zhang, F. Wang, X. Huang, et al., “Engineered Sensory Nerve Guides Self-Adaptive Bone Healing via NGF-TrkA Signaling Pathway,” Advanced Science 10 (2023): 2206155.

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