Injectable hydrogels for bone regeneration: mechanical reinforcement strategies using nanoparticles and nanofibers
Review paper
DOI:
https://doi.org/10.5599/admet.3037Keywords:
Bone tissue engineering, in situ forming scaffold, nanomaterialsAbstract
Background and Purpose: The growing demand for bone regeneration following severe injuries highlights the importance of scaffolds in bone tissue engineering (BTE). Injectable hydrogels have emerged as promising candidates because their properties closely mimic the native extracellular matrix (ECM). However, their limited mechanical strength and structural instability restrict their practical application. Approach: This review summarizes recent strategies for reinforcing in situ-forming injectable hydrogels to improve their mechanical performance for bone regeneration. Particular emphasis is placed on nanomaterial-based strategies, including the incorporation of nanoparticles and nanofibers, and their ability to enhance the physical properties of polymeric networks. Key Results: Evidence from recent studies demonstrates that reinforcing hydrogels with nano-scaled materials creates interconnected networks that improve load-bearing capacity, stability, and resistance to deformation. These reinforced systems retain the inherent advantages of injectable hydrogels-biocompatibility, biodegradability, permeability to oxygen and nutrients, and drug delivery capability-while addressing their mechanical shortcomings. Conclusion: Nanomaterial-based reinforcement offers a versatile approach to overcoming the limitations of injectable hydrogels in BTE. By providing improved structural integrity alongside biological functionality, these advanced systems broaden the potential of injectable hydrogels for clinical translation. Future work should focus on optimizing reinforcement strategies to balance mechanical enhancement with safety, manufacturability, and regulatory considerations.
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References
[1] P.M. Sivakumar, A.A. Yetisgin, S.B. Sahin, E. Demir, S. Cetinel. Bone tissue engineering: Anionic polysaccharides as promising scaffolds. Carbohydrate Polymers 283 (2022) 119142. https://dx.doi.org/10.1016/j.carbpol.2022.119142 DOI: https://doi.org/10.1016/j.carbpol.2022.119142
[2] L.M. Biga, S. Dawson, A. Harwell, R. Hopkins, J. Kaufmann, M. LeMaster, P. Matern, K. Morrison-Graham, D. Quick, J. Runyeon. Anatomy & Physiology. OpenStax, Houston, USA, 2020. https://open.oregonstate.education/anatomy2e/chapter/bone-structure/ (Accessed: May 8, 2024).
[3] J.L. Brown, C.T. Laurencin. Bone Tissue Engineering, in Biomaterials Science, W.R. Wagner, S.E. Sakiyama-Elbert, G. Zhang, M.J. Yaszemski, Ed(s)., Academic Press, Cambridge, USA, 2020, p. 1373-1388. https://dx.doi.org/10.1016/b978-0-12-816137-1.00085-4 DOI: https://doi.org/10.1016/B978-0-12-816137-1.00085-4
[4] E. Bilgiç, Ö. Boyacıoğlu, M. Gizer, P. Korkusuz, F. Korkusuz. Architecture of bone tissue and its adaptation to pathological conditions, in Comparative Kinesiology of the Human Body, S. Angin, I.E. Şimşek, Ed(s)., Academic Press, Cambridge, USA, 2020, p. 71-90. https://dx.doi.org/10.1016/b978-0-12-812162-7.00006-0 DOI: https://doi.org/10.1016/B978-0-12-812162-7.00006-0
[5] Z. Li, W. Kong. Cellular signaling in Abdominal Aortic Aneurysm. Cellular Signalling 70 (2020) 109575. https://dx.doi.org/10.1016/j.cellsig.2020.109575 DOI: https://doi.org/10.1016/j.cellsig.2020.109575
[6] P. Sharma, R.K. Sharma, K. Gaur. Understanding the impact of diabetes on bone health: A clinical review. Metabolism Open 24 (2024) 100330. https://dx.doi.org/10.1016/j.metop.2024.100330 DOI: https://doi.org/10.1016/j.metop.2024.100330
[7] G.A. Renders, L. Mulder, L.J. van Ruijven, T.M. van Eijden. Porosity of human mandibular condylar bone. Journal of Anatomy 210 (2007) 239-248. https://dx.doi.org/10.1111/j.1469-7580.2007.00693.x DOI: https://doi.org/10.1111/j.1469-7580.2007.00693.x
[8] T. Nakano, Y. Tabata, Y. Umakoshi. Texture and Bone Reinforcement, in Comprehensive Structural Integrity, I. Milne, R.O. Ritchie, B. Karihaloo, Ed(s)., Elsevier, Oxford, UK, 2005, p. 1-8. https://dx.doi.org/10.1016/B0-08-043152-6/02061-1 DOI: https://doi.org/10.1016/B0-08-043152-6/02061-1
[9] E.F. Morgan, G.U. Unnikrisnan, A.I. Hussein. Bone Mechanical Properties in Healthy and Diseased States. Annual Review of Biomedical Engineering 20 (2018) 119-143. https://dx.doi.org/10.1146/annurev-bioeng-062117-121139 DOI: https://doi.org/10.1146/annurev-bioeng-062117-121139
[10] R.C. Singleton, G.M. Pharr, J.S. Nyman. Increased tissue-level storage modulus and hardness with age in male cortical bone and its association with decreased fracture toughness. Bone 148 (2021) 115949. https://dx.doi.org/10.1016/j.bone.2021.115949 DOI: https://doi.org/10.1016/j.bone.2021.115949
[11] D. Lacroix. 3 - Biomechanical aspects of bone repair, in Bone Repair Biomaterials (Second Edition), K.M. Pawelec, J.A. Planell, Ed(s)., Woodhead Publishing, Duxford, UK, 2019, p. 53-64. https://dx.doi.org/10.1016/B978-0-08-102451-5.00003-2 DOI: https://doi.org/10.1016/B978-0-08-102451-5.00003-2
[12] R.B. Ashman, J.Y. Rho. Elastic modulus of trabecular bone material. Journal of Biomechanics 21 (1988) 177-181. https://dx.doi.org/10.1016/0021-9290(88)90167-4 DOI: https://doi.org/10.1016/0021-9290(88)90167-4
[13] J.Y. Rho, R.B. Ashman, C.H. Turner. Young's modulus of trabecular and cortical bone material: ultrasonic and microtensile measurements. Journal of Biomechanics 26 (1993) 111-119. https://dx.doi.org/10.1016/0021-9290(93)90042-d DOI: https://doi.org/10.1016/0021-9290(93)90042-D
[14] D.L. Kopperdahl, T.M. Keaveny. Yield strain behavior of trabecular bone. Journal of Biomechanics 31 (1998) 601-608. https://dx.doi.org/10.1016/s0021-9290(98)00057-8 DOI: https://doi.org/10.1016/S0021-9290(98)00057-8
[15] S. Hu, J. Li, L. Liu, R. Dai, Z. Sheng, X. Wu, X. Feng, X. Yao, E. Liao, E. Keller, Y. Jiang. Micro/Nanostructures and Mechanical Properties of Trabecular Bone in Ovariectomized Rats. International Journal of Endocrinology 2015 (2015) 252503. https://dx.doi.org/10.1155/2015/252503 DOI: https://doi.org/10.1155/2015/252503
[16] M. Toledano, M. Toledano-Osorio, E. Guerado, E. Caso, E. Osorio, R. Osorio. Assessing bone quality through mechanical properties in postmenopausal trabecular bone. Injury 49(S2) (2018) S3-S10. https://dx.doi.org/10.1016/j.injury.2018.07.035 DOI: https://doi.org/10.1016/j.injury.2018.07.035
[17] T. Bharadwaj, S. Chrungoo, D. Verma. Self-assembled chitosan/gelatin nanofibrous aggregates incorporated thermosensitive nanocomposite bioink for bone tissue engineering. Carbohydrate Polymers 324 (2024) 121544. https://dx.doi.org/10.1016/j.carbpol.2023.121544 DOI: https://doi.org/10.1016/j.carbpol.2023.121544
[18] N. Xue, X. Ding, R. Huang, R. Jiang, H. Huang, X. Pan, W. Min, J. Chen, J.A. Duan, P. Liu, Y. Wang. Bone Tissue Engineering in the Treatment of Bone Defects. Pharmaceuticals 15 (2022) 879. https://dx.doi.org/10.3390/ph15070879 DOI: https://doi.org/10.3390/ph15070879
[19] L. Boaro, T. Azevedo, K. Barbosa, D. Camarena, C. Troncoso, L. Catalani, M. Moreira, F. Gonçalves. Dexamethasone and vitamin D loaded scaffolds for bone engineering. Research Square Preprint (2024). https://dx.doi.org/10.21203/rs.3.rs-3897927/v1 DOI: https://doi.org/10.21203/rs.3.rs-3897927/v1
[20] H. Qu, H. Fu, Z. Han, Y. Sun. Biomaterials for bone tissue engineering scaffolds: a review. RSC Advances 9 (2019) 26252-26262. https://dx.doi.org/10.1039/C9RA05214C DOI: https://doi.org/10.1039/C9RA05214C
[21] J. Liu, L. Yang, K. Liu, F. Gao. Hydrogel scaffolds in bone regeneration: Their promising roles in angiogenesis. Frontiers in Pharmacology 14 (2023) 1050954. https://dx.doi.org/10.3389/fphar.2023.1050954 DOI: https://doi.org/10.3389/fphar.2023.1050954
[22] N. Olov, S. Bagheri-Khoulenjani, H. Mirzadeh. Injectable hydrogels for bone and cartilage tissue engineering: a review. Progress in Biomaterials 11 (2022) 113-135. https://dx.doi.org/10.1007/s40204-022-00185-8 DOI: https://doi.org/10.1007/s40204-022-00185-8
[23] M. Liu, X. Zeng, C. Ma, H. Yi, Z. Ali, X. Mou, S. Li, Y. Deng, N. He. Injectable hydrogels for cartilage and bone tissue engineering. Bone Research 5 (2017) 17014. https://dx.doi.org/10.1038/boneres.2017.14 DOI: https://doi.org/10.1038/boneres.2017.14
[24] H.-S. Kim, J. Jang, J.-S. Oh, E.-J. Lee, C.-M. Han, U.S. Shin. Injectable remodeling hydrogels derived from alendronate-tethered alginate calcium complex for enhanced osteogenesis. Carbohydrate Polymers 303 (2023) 120473. https://dx.doi.org/10.1016/j.carbpol.2023.120473 DOI: https://doi.org/10.1016/j.carbpol.2022.120473
[25] J.H. Lee. Injectable hydrogels delivering therapeutic agents for disease treatment and tissue engineering. Biomaterials Research 22 (2018) 27. https://dx.doi.org/10.1186/s40824-018-0138-6 DOI: https://doi.org/10.1186/s40824-018-0138-6
[26] X. Yu, X. Wang, D. Li, R. Sheng, Y. Qian, R. Zhu, X. Wang, K. Lin. Mechanically reinforced injectable bioactive nanocomposite hydrogels for in-situ bone regeneration. Chemical Engineering Journal 433 (2022) 132799. https://dx.doi.org/10.1016/j.cej.2022.132799 DOI: https://doi.org/10.1016/j.cej.2021.132799
[27] B. Bakhshandeh, S.G. Sorboni, N. Ranjbar, R. Deyhimfar, M.S. Abtahi, M. Izady, N. Kazemi, A. Noori, C.P. Pennisi. Mechanotransduction in tissue engineering: Insights into the interaction of stem cells with biomechanical cues. Experimental Cell Research 431 (2023 113766. https://dx.doi.org/10.1016/j.yexcr.2023.113766 DOI: https://doi.org/10.1016/j.yexcr.2023.113766
[28] S.B. Han, J.K. Kim, G. Lee, D.H. Kim. Mechanical Properties of Materials for Stem Cell Differentiation. Advanced Biosystems 4 (2020) e2000247. https://dx.doi.org/10.1002/adbi.202000247 DOI: https://doi.org/10.1002/adbi.202000247
[29] S.A. Irvine, S.S. Venkatraman. Bioprinting and Differentiation of Stem Cells. Molecules 21 (2016) 1188. https://dx.doi.org/10.3390/molecules21091188 DOI: https://doi.org/10.3390/molecules21091188
[30] K.J. De France, E.D. Cranston, T. Hoare. Mechanically Reinforced Injectable Hydrogels. ACS Applied Polymer Materials 2 (2020) 1016-1030. https://dx.doi.org/10.1021/acsapm.9b00981 DOI: https://doi.org/10.1021/acsapm.9b00981
[31] W. Ma, M. Yang, C. Wu, S. Wang, M. Du. Bioinspired self-healing injectable nanocomposite hydrogels based on oxidized dextran and gelatin for growth-factor-free bone regeneration. International Journal of Biological Macromolecules 251 (2023) 126145. https://dx.doi.org/10.1016/j.ijbiomac.2023.126145 DOI: https://doi.org/10.1016/j.ijbiomac.2023.126145
[32] S. Li, Y. Qing, Y. Lou, R. Li, H. Wang, X. Wang, B. Ying, X. Tang, Y. Qin. Injectable thermosensitive black phosphorus nanosheet- and doxorubicin-loaded hydrogel for synergistic bone tumor photothermal-chemotherapy and osteogenesis enhancement. International Journal of Biological Macromolecules 239 (2023) 124209. https://dx.doi.org/10.1016/j.ijbiomac.2023.124209 DOI: https://doi.org/10.1016/j.ijbiomac.2023.124209
[33] X. Liu, Y. Zhang, Z. Hussain, P. Zheng, M. Xu, H. Zhao, Y. Liu, Y. Cao, I. Ullah, A. Osaka, R. Pei. Self-biomineralized in situ injectable CaSO4 nanorods-enriched collagen-hyaluronic acid composite hydrogels for biomimetic bone reconstruction in a minimally invasive manner. Applied Materials Today 30 (2023) 101693. https://dx.doi.org/10.1016/j.apmt.2022.101693 DOI: https://doi.org/10.1016/j.apmt.2022.101693
[34] Y. Li, D. Zhao, Z. Wang, Y. Meng, B. Liu, L. Li, R. Liu, S. Dong, F. Wei. Minimally invasive bone augmentation through subperiosteal injectable hydroxylapatite/laponite/alginate nanocomposite hydrogels. International Journal of Biological Macromolecules 231 (2023) 123232. https://dx.doi.org/10.1016/j.ijbiomac.2023.123232 DOI: https://doi.org/10.1016/j.ijbiomac.2023.123232
[35] M. Ghorbani, E. Vasheghani-Farahani, N. Azarpira, S. Hashemi-Najafabadi, A. Ghasemi. Dual-crosslinked in-situ forming alginate/silk fibroin hydrogel with potential for bone tissue engineering. Biomaterials Advances 153 (2023) 213565. https://dx.doi.org/10.1016/j.bioadv.2023.213565 DOI: https://doi.org/10.1016/j.bioadv.2023.213565
[36] S. Cui, S. Zhang, S. Coseri. An injectable and self-healing cellulose nanofiber-reinforced alginate hydrogel for bone repair. Carbohydrate Polymers 300 (2023) 120243. https://dx.doi.org/10.1016/j.carbpol.2022.120243 DOI: https://doi.org/10.1016/j.carbpol.2022.120243
[37] W. Lu, M. Zeng, W. Liu, T. Ma, X. Fan, H. Li, Y. Wang, H. Wang, Y. Hu, J. Xie. Human urine-derived stem cell exosomes delivered via injectable GelMA templated hydrogel accelerate bone regeneration. Materials Today Bio 19(2023) 100569. https://dx.doi.org/10.1016/j.mtbio.2023.100569 DOI: https://doi.org/10.1016/j.mtbio.2023.100569
[38] A. Zheng, X. Wang, X. Xin, L. Peng, T. Su, L. Cao, X. Jiang. Promoting lacunar bone regeneration with an injectable hydrogel adaptive to the microenvironment. Bioactive Materials 21 (2023) 403-421. https://dx.doi.org/10.1016/j.bioactmat.2022.08.031 DOI: https://doi.org/10.1016/j.bioactmat.2022.08.031
[39] Y. Miao, T. Lu, S. Cui, Z. Xu, X. Liu, Y. Zhang. Engineering natural DNA matrices with halloysite nanotubes to fabricate injectable therapeutic hydrogels for bone regeneration. Journal of Orthopaedic Translation 49 (2024) 218-229. https://dx.doi.org/10.1016/j.jot.2024.09.010 DOI: https://doi.org/10.1016/j.jot.2024.09.010
[40] B. Liu, J. Li, X. Lei, S. Miao, S. Zhang, P. Cheng, Y. Song, H. Wu, Y. Gao, L. Bi, G. Pei. Cell-loaded injectable gelatin/alginate/LAPONITE® nanocomposite hydrogel promotes bone healing in a critical-size rat calvarial defect model. RSC Advances 10 (2020) 25652-25661. https://dx.doi.org/10.1039/d0ra03040f DOI: https://doi.org/10.1039/D0RA03040F
[41] S. Zhou, C. Xiao, L. Fan, J. Yang, R. Ge, M. Cai, K. Yuan, C. Li, R.W. Crawford, Y. Xiao, P. Yu, C. Deng, C. Ning, L. Zhou, Y. Wang. Injectable ultrasound-powered bone-adhesive nanocomposite hydrogel for electrically accelerated irregular bone defect healing. Journal of Nanobiotechnology 22 (2024) 54. https://dx.doi.org/10.1186/s12951-024-02320-y DOI: https://doi.org/10.1186/s12951-024-02320-y
[42] H. Byun, G.N. Jang, H. Jeong, J. Lee, S.J. Huh, S. Lee, E. Kim, H. Shin. Development of a composite hydrogel incorporating anti-inflammatory and osteoinductive nanoparticles for effective bone regeneration. Biomaterials Research 27 (2023) 132. https://dx.doi.org/10.1186/s40824-023-00473-9 DOI: https://doi.org/10.1186/s40824-023-00473-9
[43] Y. Zhu, H. Liu, P. Wu, Y. Chen, Z. Deng, L. Cai, M. Wu. Multifunctional injectable hydrogel system as a mild photothermal-assisted therapeutic platform for programmed regulation of inflammation and osteo-microenvironment for enhanced healing of diabetic bone defects in situ. Theranostics 14 (2024) 7140-7198. https://dx.doi.org/10.7150/thno.102779 DOI: https://doi.org/10.7150/thno.102779
[44] Y. Xu, S. Zheng, Z. Tang, Q. Zhong, R. Chen, P. Wang, J. Fu, J. Xie, Y. Ning, M. Lei, D. Wang, H. Mai, H. Li, C. Sun, Z. Shi, H. Cheng, Z. Shi. Injectable, oxygen-releasing, thermosensitive hydrogel promotes vascularized bone formation with prolonged oxygen delivery and improved osteoinductivity. Materials Today Bio 29 (2024) 101267. https://dx.doi.org/10.1016/j.mtbio.2024.101267 DOI: https://doi.org/10.1016/j.mtbio.2024.101267
[45] H. Zhang, S. Ding, H. Xue, S. Wang, X. Quan, D. Zhang, X. Liu, H. Tang. Injectable organic-inorganic hybrid hydrogels for bone defect repair. Frontiers in Bioengineering and Biotechnology 13 (2025) 1563546. https://dx.doi.org/10.3389/fbioe.2025.1563546 DOI: https://doi.org/10.3389/fbioe.2025.1563546
[46] M. Alipour, M. Ghorbani, M. Johari Khatoonabad, M. Aghazadeh. A novel injectable hydrogel containing polyetheretherketone for bone regeneration in the craniofacial region. Scientific Reports 13 (2023) 864. https://dx.doi.org/10.1038/s41598-022-23708-6 DOI: https://doi.org/10.1038/s41598-022-23708-6
[47] A. Ozgen, B. Kilic, M. Ghaffarlou, C. Karaaslan, H.M. Aydin. Injectable carboxymethyl chitosan/oxidized dextran hydrogels containing zoledronic acid modified strontium hydroxyapatite nanoparticles. RSC Advances 15 (2025) 4014-4028. https://dx.doi.org/10.1039/d4ra08123d DOI: https://doi.org/10.1039/D4RA08123D
[48] H. Zhang, Y. Wang, W. Qiao, X. Hu, H. Qiang, K. Xia, L. Du, L. Yang, Y. Bao, J. Gao, T. Zhang, Z. Yu. An injectable multifunctional nanocomposite hydrogel promotes vascularized bone regeneration by regulating macrophages. Journal of Nanobiotechnology 23 (2025) 283. https://dx.doi.org/10.1186/s12951-025-03358-2 DOI: https://doi.org/10.1186/s12951-025-03358-2
[49] X. Zhang, K. Nan, Y. Zhang, K. Song, Z. Geng, D. Shang, X. Guan, L. Fan. A novel injectable hydrogel prepared from phenylboronic acid modified gelatin and oxidized-dextran for bone tissue engineering. International Journal of Biological Macromolecules 261 (2024) 129666. https://dx.doi.org/10.1016/j.ijbiomac.2024.129666 DOI: https://doi.org/10.1016/j.ijbiomac.2024.129666
[50] Z.C. Hu, J.Q. Lu, T.W. Zhang, H.F. Liang, H. Yuan, D.H. Su, W. Ding, R.X. Lian, Y.X. Ge, B. Liang, J. Dong, X.G. Zhou, L.B. Jiang. Piezoresistive MXene/Silk fibroin nanocomposite hydrogel for accelerating bone regeneration by Re-establishing electrical microenvironment. Bioactive Materials 22 (2023) 1-17. https://dx.doi.org/10.1016/j.bioactmat.2022.08.025 DOI: https://doi.org/10.1016/j.bioactmat.2022.08.025
[51] J. Li, Z. Fan, Z. Guan, J. Ruan. Injectable MXene/Ag-HA composite hydrogel for enhanced alveolar bone healing and mechanistic study. Frontiers in Bioengineering and Biotechnology 12 (2024) 1485437. https://dx.doi.org/10.3389/fbioe.2024.1485437 DOI: https://doi.org/10.3389/fbioe.2024.1485437
[52] W. Ma, H. Chen, S. Cheng, C. Wu, L. Wang, M. Du. Gelatin hydrogel reinforced with mussel-inspired polydopamine-functionalized nanohydroxyapatite for bone regeneration. International Journal of Biological Macromolecules 240 (2023) 124287. https://dx.doi.org/10.1016/j.ijbiomac.2023.124287 DOI: https://doi.org/10.1016/j.ijbiomac.2023.124287
[53] M.P.B. Rajula, V. Narayanan, G.D. Venkatasubbu, R.C. Mani, A. Sujana. Nano-hydroxyapatite: A Driving Force for Bone Tissue Engineering. Journal of Pharmacy and Bioallied Sciences 13 (2021) S11-S14. https://dx.doi.org/10.4103/jpbs.JPBS_683_20 DOI: https://doi.org/10.4103/jpbs.JPBS_683_20
[54] V. Saxena, L. Pandey. Synthesis and Sintering of Calcium Hydroxyapatite for Biomedical Applications, in Encyclopedia of Materials: Technical Ceramics and Glasses, M. Pomeroy, Ed(s)., Elsevier, Oxford, UK, 2021, p. 364-375. https://dx.doi.org/10.1016/B978-0-12-820352-1.00136-X DOI: https://doi.org/10.1016/B978-0-12-820352-1.00136-X
[55] X. Zhou, J. Sun, K. Wo, H. Wei, H. Lei, J. Zhang, X. Lu, F. Mei, Q. Tang, Y. Wang, Z. Luo, L. Fan, Y. Chu, L. Chen. nHA-loaded gelatin/alginate hydrogel with combined physical and bioactive features for maxillofacial bone repair. Carbohydrate Polymers 298 (2022) 120127. https://dx.doi.org/10.1016/j.carbpol.2022.120127 DOI: https://doi.org/10.1016/j.carbpol.2022.120127
[56] B. Zhao, M. Zhao, L. Li, S. Sun, H. Yu, Y. Cheng, Y. Yang, Y. Fan, Y. Sun. Preparation and Properties of Double-Crosslinked Hydroxyapatite Composite Hydrogels. International Journal of Molecular Sciences 23 (2022) 9962. https://dx.doi.org/10.3390/ijms23179962 DOI: https://doi.org/10.3390/ijms23179962
[57] S. Mondal, S. Park, J. Choi, T.T.H. Vu, V.H.M. Doan, T.T. Vo, B. Lee, J. Oh. Hydroxyapatite: A journey from biomaterials to advanced functional materials. Advances in Colloid and Interface Science 321 (2023) 103013. https://dx.doi.org/10.1016/j.cis.2023.103013 DOI: https://doi.org/10.1016/j.cis.2023.103013
[58] S. Utech, A.R. Boccaccini. A review of hydrogel-based composites for biomedical applications: enhancement of hydrogel properties by addition of rigid inorganic fillers. Journal of Materials Science 51 (2016) 271-310. https://dx.doi.org/10.1007/s10853-015-9382-5 DOI: https://doi.org/10.1007/s10853-015-9382-5
[59] G.K. Wasupalli, D. Verma. Injectable and thermosensitive nanofibrous hydrogel for bone tissue engineering. Materials Science and Engineering: C 107 (2020) 110343. https://dx.doi.org/10.1016/j.msec.2019.110343 DOI: https://doi.org/10.1016/j.msec.2019.110343
[60] P. Ma, W. Wu, Y. Wei, L. Ren, S. Lin, J. Wu. Biomimetic gelatin/chitosan/polyvinyl alcohol/nano-hydroxyapatite scaffolds for bone tissue engineering. Materials & Design 207 (2021) 109865. https://dx.doi.org/10.1016/j.matdes.2021.109865 DOI: https://doi.org/10.1016/j.matdes.2021.109865
[61] R. Arun Kumar, A. Sivashanmugam, S. Deepthi, S. Iseki, K.P. Chennazhi, S.V. Nair, R. Jayakumar. Injectable Chitin-Poly(ε-caprolactone)/Nanohydroxyapatite Composite Microgels Prepared by Simple Regeneration Technique for Bone Tissue Engineering. ACS Applied Materials & Interfaces 7 (2015) 9399-9409. https://dx.doi.org/10.1021/acsami.5b02685 DOI: https://doi.org/10.1021/acsami.5b02685
[62] Z. Chen, M. Jia, Y. Liu, H. Zhou, X. Wang, M. Wu. Injectable Composite Hydrogel Stents for Bone Defect Management with Enhanced Osteogenesis and Angiogenesis. International Journal of Nanomedicine 20 (2025) 4589-4606. https://dx.doi.org/10.2147/IJN.S509686 DOI: https://doi.org/10.2147/IJN.S509686
[63] S. Fu, G. Guo, C. Gong, S. Zeng, H. Liang, F. Luo, X. Zhang, X. Zhao, Y. Wei, Z. Qian. The Journal of Physical Chemistry B 113 (2009) 16518-16525. https://dx.doi.org/10.1021/jp907974d DOI: https://doi.org/10.1021/jp907974d
[64] A.M. El-Kady, E.M. Mahmoud, M. Sayed, S.M. Kamel, S.M. Naga. In-vitro and in-vivo evaluation for the bio-natural Alginate/nano-Hydroxyapatite (Alg/n-HA) injectable hydrogel for critical size bone substitution. International Journal of Biological Macromolecules 253(2023) 126618. https://dx.doi.org/10.1016/j.ijbiomac.2023.126618 DOI: https://doi.org/10.1016/j.ijbiomac.2023.126618
[65] J. Zheng, Y. Wang, Y. Wang, R. Duan, L. Liu. Gelatin/Hyaluronic Acid Photocrosslinked Double Network Hydrogel with Nano-Hydroxyapatite Composite for Potential Application in Bone Repair. Gels 9 (2023) 742. https://dx.doi.org/10.3390/gels9090742 DOI: https://doi.org/10.3390/gels9090742
[66] S.J. Lee, H.-J. Kim, E.J. Choi, H. Kim, D. Lee, S.-H. An, S.J. Min, W.-K. Ko, J.S. Lee, H. Nah. Carbohydrate Polymer Technologies and Applications 8 (2024) 100625. https://dx.doi.org/10.1016/j.carpta.2024.100625 DOI: https://doi.org/10.1016/j.carpta.2024.100625
[67] A. Daneshvar, M. Farokhi, S. Bonakdar, M. Vossoughi. Synthesis and characterization of injectable thermosensitive hydrogel based on Pluronic-grafted silk fibroin copolymer containing hydroxyapatite nanoparticles as potential for bone tissue engineering. International Journal of Biological Macromolecules 277 (2024) 134412. https://dx.doi.org/10.1016/j.ijbiomac.2024.134412 DOI: https://doi.org/10.1016/j.ijbiomac.2024.134412
[68] S.P. Uswatta, I.U. Okeke, A.C. Jayasuriya. Injectable porous nano-hydroxyapatite/ chitosan/ tripoly-phosphate scaffolds with improved compressive strength for bone regeneration. Materials Science and Engineering: C 69 (2016) 505-512. https://dx.doi.org/10.1016/j.msec.2016.06.089 DOI: https://doi.org/10.1016/j.msec.2016.06.089
[69] D. Mishra, B. Bhunia, I. Banerjee, P. Datta, S. Dhara, T.K. Maiti. Materials Science and Engineering: C 31 (2011) 1295-1304. https://dx.doi.org/10.1016/j.msec.2011.04.007 DOI: https://doi.org/10.1016/j.msec.2011.04.007
[70] N. Eliaz, N. Metoki. Calcium Phosphate Bioceramics: A Review of Their History, Structure, Properties, Coating Technologies and Biomedical Applications. Materials 10 (2017) 334. https://dx.doi.org/10.3390/ma10040334 DOI: https://doi.org/10.3390/ma10040334
[71] L. Nie, Q. Wu, H. Long, K. Hu, P. Li, C. Wang, M. Sun, J. Dong, X. Wei, J. Suo, D. Hua, S. Liu, H. Yuan, S. Yang. Development of chitosan/gelatin hydrogels incorporation of biphasic calcium phosphate nanoparticles for bone tissue engineering. Journal of Biomaterials Science, Polymer Edition 30 (2019) 1636-1657. https://dx.doi.org/10.1080/09205063.2019.1654210 DOI: https://doi.org/10.1080/09205063.2019.1654210
[72] M.H. Kim, B.S. Kim, H. Park, J. Lee, W.H. Park. Injectable methylcellulose hydrogel containing calcium phosphate nanoparticles for bone regeneration. International Journal of Biological Macromolecules 109 (2018) 57-64. https://dx.doi.org/10.1016/j.ijbiomac.2017.12.068 DOI: https://doi.org/10.1016/j.ijbiomac.2017.12.068
[73] S. Samavedi, L.K. Poindexter, M. Van Dyke, A.S. Goldstein. Synthetic biomaterials for regenerative medicine applications, in Regenerative Medicine Applications in Organ Transplantation, G. Orlando, J.J. Yoo, A. Atala, S. Soker, Ed(s)., Elsevier, Boston, USA, 2014, p. 81-99. https://dx.doi.org/10.1016/B978-0-12-398523-1.00007-0 DOI: https://doi.org/10.1016/B978-0-12-398523-1.00007-0
[74] F. Zhao, Z. Yang, H. Xiong, Y. Yan, X. Chen, L. Shao. A bioactive glass functional hydrogel enhances bone augmentation via synergistic angiogenesis, self-swelling and osteogenesis. Bioactive Materials 22 (2023) 201-210. https://dx.doi.org/10.1016/j.bioactmat.2022.09.007 DOI: https://doi.org/10.1016/j.bioactmat.2022.09.007
[75] A.M. Abd El-Aziz, A. Abd El-Fattah, A. El-Maghraby, D.A. Ghareeb, S. Kandil. Viscoelasticity, Mechanical Properties, and In Vitro Bioactivity of Gelatin/Borosilicate Bioactive Glass Nanocomposite Hydrogels as Potential Scaffolds for Bone Regeneration. Polymers 13 (2021) 2014. https://dx.doi.org/10.3390/polym13122014 DOI: https://doi.org/10.3390/polym13122014
[76] M.N. Rahaman, D.E. Day, B.S. Bal, Q. Fu, S.B. Jung, L.F. Bonewald, A.P. Tomsia. Bioactive glass in tissue engineering. Acta Biomaterialia 7 (2011) 2355-2373. https://dx.doi.org/10.1016/j.actbio.2011.03.016 DOI: https://doi.org/10.1016/j.actbio.2011.03.016
[77] X. Ding, J. Shi, J. Wei, Y. Li, X. Wu, Y. Zhang, X. Jiang, X. Zhang, H. Lai. A biopolymer hydrogel electrostatically reinforced by amino-functionalized bioactive glass for accelerated bone regeneration. Science Advances 7 (2021) eabj7857. https://dx.doi.org/10.1126/sciadv.abj7857 DOI: https://doi.org/10.1126/sciadv.abj7857
[78] R. Sreena, G. Raman, G. Manivasagam, A.J. Nathanael. Bioactive glass-polymer nanocomposites: a comprehensive review on unveiling their biomedical applications. Journal of Materials Chemistry B 12 (2024) 11278-11301. https://dx.doi.org/10.1039/D4TB01525H DOI: https://doi.org/10.1039/D4TB01525H
[79] C.D. Moreira, S.M. Carvalho, R.G. Sousa, H.S. Mansur, M.M. Pereira. Nanostructured chitosan/gelatin/bioactive glass in situ forming hydrogel composites as a potential injectable matrix for bone tissue engineering. Materials Chemistry and Physics 218 (2018) 304-316. https://dx.doi.org/10.1016/j.matchemphys.2018.07.039 DOI: https://doi.org/10.1016/j.matchemphys.2018.07.039
[80] S. Amirthalingam, S.S. Lee, M. Pandian, J. Ramu, S. Iyer, N.S. Hwang, R. Jayakumar. Combinatorial effect of nano whitlockite/nano bioglass with FGF-18 in an injectable hydrogel for craniofacial bone regeneration. Biomaterials Science 9 (2021) 2439-2453. https://dx.doi.org/10.1039/d0bm01496f DOI: https://doi.org/10.1039/D0BM01496F
[81] S. Batool, U. Liaqat, B. Babar, Z. Hussain. Bone whitlockite: synthesis, applications, and future prospects. Journal of the Korean Ceramic Society 58 (2021) 530-547. https://dx.doi.org/10.1007/s43207-021-00120-w DOI: https://doi.org/10.1007/s43207-021-00120-w
[82] S. Batool, U. Liaqat, Z. Hussain. Preparation and physicochemical characterization of whitlockite/PVA/Gelatin composite for bone tissue regeneration. Frontiers in Chemistry 12 (2024) 1355545. https://dx.doi.org/10.3389/fchem.2024.1355545 DOI: https://doi.org/10.3389/fchem.2024.1355545
[83] H. Cheng, R. Chabok, X. Guan, A. Chawla, Y. Li, A. Khademhosseini, H.L. Jang. Synergistic interplay between the two major bone minerals, hydroxyapatite and whitlockite nanoparticles, for osteogenic differentiation of mesenchymal stem cells. Acta Biomaterialia 69 (2018) 342-351. https://dx.doi.org/10.1016/j.actbio.2018.01.016 DOI: https://doi.org/10.1016/j.actbio.2018.01.016
[84] S. Amirthalingam, A. Ramesh, S.S. Lee, N.S. Hwang, R. Jayakumar. Injectable in Situ Shape-Forming Osteogenic Nanocomposite Hydrogel for Regenerating Irregular Bone Defects. ACS Applied Bio Materials 1 (2018) 1037-1046. https://dx.doi.org/10.1021/acsabm.8b00225 DOI: https://doi.org/10.1021/acsabm.8b00225
[85] R. Yegappan, V. Selvaprithiviraj, S. Amirthalingam, A. Mohandas, N.S. Hwang, R. Jayakumar. Injectable angiogenic and osteogenic carrageenan nanocomposite hydrogel for bone tissue engineering. International Journal of Biological Macromolecules 122 (2019) 320-328. https://dx.doi.org/10.1016/j.ijbiomac.2018.10.182 DOI: https://doi.org/10.1016/j.ijbiomac.2018.10.182
[86] L.R.M. de Andrade, L.N. Andrade, J.O. Bahú, V.O. Cárdenas Concha, A.T. Machado, D.S. Pires, R. Santos, T.F.M. Cardoso, J.C. Cardoso, R.L.C. Albuquerque-Junior, P. Severino, E.B. Souto. Biomedical applications of carbon nanotubes: A systematic review of data and clinical trials. Journal of Drug Delivery Science and Technology 99 (2024) 105932. https://doi.org/10.1016/j.jddst.2024.105932 DOI: https://doi.org/10.1016/j.jddst.2024.105932
[87] S.R. Shin, S.M. Jung, M. Zalabany, K. Kim, P. Zorlutuna, S.b. Kim, M. Nikkhah, M. Khabiry, M. Azize, J. Kong, K.-t. Wan, T. Palacios, M.R. Dokmeci, H. Bae, X. Tang, A. Khademhosseini. Carbon-Nanotube-Embedded Hydrogel Sheets for Engineering Cardiac Constructs and Bioactuators. ACS Nano 7 (2013) 2369-2380. https://dx.doi.org/10.1021/nn305559j DOI: https://doi.org/10.1021/nn305559j
[88] J. Zhao, F. Wang, X. Zhang, L. Liang, X. Yang, Q. Li, X. Zhang. Vibration Damping of Carbon Nanotube Assembly Materials. arXiv 1711 (2017) 00623. https://dx.doi.org/10.48550/arXiv.1711.00623 DOI: https://doi.org/10.1002/adem.201700647
[89] A. Vashist, A. Kaushik, A. Vashist, V. Sagar, A. Ghosal, Y.K. Gupta, S. Ahmad, M. Nair. Advances in Carbon Nanotubes-Hydrogel Hybrids in Nanomedicine for Therapeutics. Advanced Healthcare Materials 7 (2018) e1701213. https://dx.doi.org/10.1002/adhm.201701213 DOI: https://doi.org/10.1002/adhm.201701213
[90] K. Kaur, S.S. Paiva, D. Caffrey, B.L. Cavanagh, C.M. Murphy. Injectable chitosan/collagen hydrogels nano-engineered with functionalized single wall carbon nanotubes for minimally invasive applications in bone. Materials Science and Engineering: C 128(2021) 112340. https://dx.doi.org/10.1016/j.msec.2021.112340 DOI: https://doi.org/10.1016/j.msec.2021.112340
[91] X. Liu, M.N. George, L. Li, D. Gamble, A.L. Miller Ii, B. Gaihre, B.E. Waletzki, L. Lu. Injectable Electrical Conductive and Phosphate Releasing Gel with Two-Dimensional Black Phosphorus and Carbon Nanotubes for Bone Tissue Engineering. ACS Biomaterials Science & Engineering 6 (2020) 4653-4665. https://dx.doi.org/10.1021/acsbiomaterials.0c00612 DOI: https://doi.org/10.1021/acsbiomaterials.0c00612
[92] K. Fakhruddin, R. Hassan, M.U.A. Khan, S.N. Allisha, S.I. Abd Razak, M.H. Zreaqat, H.F.M. Latip, M.N. Jamaludin, A. Hassan. Halloysite nanotubes and halloysite-based composites for biomedical applications. Arabian Journal of Chemistry 14 (2021) 103294. https://dx.doi.org/10.1016/j.arabjc.2021.103294 DOI: https://doi.org/10.1016/j.arabjc.2021.103294
[93] Y. Wu, Y. Zhang, J. Ju, H. Yan, X. Huang, Y. Tan. Advances in Halloysite Nanotubes-Polysaccharide Nanocomposite Preparation and Applications. Polymers 11 (2019) 987. https://dx.doi.org/10.3390/polym11060987 DOI: https://doi.org/10.3390/polym11060987
[94] B. Roushangar Zineh, M.R. Shabgard, L. Roshangar. An Experimental Study on the Mechanical and Biological Properties of Bio-Printed Alginate/Halloysite Nanotube/Methylcellulose/Russian Olive-Based Scaffolds. Advanced Pharmaceutical Bulletin 8 (2018) 643-655. https://dx.doi.org/10.15171/apb.2018.073 DOI: https://doi.org/10.15171/apb.2018.073
[95] F. Kazemi-Aghdam, V. Jahed, M. Dehghan-Niri, F. Ganji, E. Vasheghani-Farahani. Injectable chitosan hydrogel embedding modified halloysite nanotubes for bone tissue engineering. Carbohydrate Polymers 269 (2021) 118311. https://dx.doi.org/10.1016/j.carbpol.2021.118311 DOI: https://doi.org/10.1016/j.carbpol.2021.118311
[96] L. Yavari Maroufi, M. Ghorbani. Injectable chitosan-quince seed gum hydrogels encapsulated with curcumin loaded-halloysite nanotubes designed for tissue engineering application. International Journal of Biological Macromolecules 177 (2021) 485-494. https://dx.doi.org/10.1016/j.ijbiomac.2021.02.113 DOI: https://doi.org/10.1016/j.ijbiomac.2021.02.113
[97] M. Janmohammadi, Z. Nazemi, A.O.M. Salehi, A. Seyfoori, J.V. John, M.S. Nourbakhsh, M. Akbari. Cellulose-based composite scaffolds for bone tissue engineering and localized drug delivery. Bioactive Materials 20 (2023) 137-163. https://dx.doi.org/10.1016/j.bioactmat.2022.05.018 DOI: https://doi.org/10.1016/j.bioactmat.2022.05.018
[98] R.J. Hickey, A.E. Pelling. Cellulose Biomaterials for Tissue Engineering. Frontiers in Bioengineering and Biotechnology 7 (2019) 45. https://dx.doi.org/10.3389/fbioe.2019.00045 DOI: https://doi.org/10.3389/fbioe.2019.00045
[99] A.K. Tamo. Nanocellulose-based hydrogels as versatile materials with interesting functional properties for tissue engineering applications. Journal of Materials Chemistry B 12 (2024) 7692-7759. https://dx.doi.org/10.1039/D4TB00397G DOI: https://doi.org/10.1039/D4TB00397G
[100] X. Huang, X. Ao, L. Yang, J. Ye, C. Wang. Preparation and properties of cellulose nanocrystal-based ion-conductive hydrogels. RSC Advances 13 (2023) 527-533. https://dx.doi.org/10.1039/D2RA04660A DOI: https://doi.org/10.1039/D2RA04660A
[101] J. Yang, C.-R. Han, J.-F. Duan, M.-G. Ma, X.-M. Zhang, F. Xu, R.-C. Sun, X.-M. Xie. Studies on the properties and formation mechanism of flexible nanocomposite hydrogels from cellulose nanocrystals and poly(acrylic acid). Journal of Materials Chemistry 22(2012) 22467-22480. https://dx.doi.org/10.1039/C2JM35498E DOI: https://doi.org/10.1039/c2jm35498e
[102] P. Nezhad-Mokhtari, M. Akrami-Hasan-Kohal, M. Ghorbani. An injectable chitosan-based hydrogel scaffold containing gold nanoparticles for tissue engineering applications. International Journal of Biological Macromolecules 154 (2020) 198-205. https://dx.doi.org/10.1016/j.ijbiomac.2020.03.112 DOI: https://doi.org/10.1016/j.ijbiomac.2020.03.112
[103] P. Maturavongsadit, G. Paravyan, R. Shrivastava, S.R. Benhabbour. Thermo-/pH-responsive chitosan-cellulose nanocrystals based hydrogel with tunable mechanical properties for tissue regeneration applications. Materialia 12 (2020) 100681. https://dx.doi.org/10.1016/j.mtla.2020.100681 DOI: https://doi.org/10.1016/j.mtla.2020.100681
[104] K. Phogat, S. Kanwar, D. Nayak, N. Mathur, S.B. Ghosh, S. Bandyopadhyay-Ghosh. Nano‐enabled poly (vinyl alcohol) based injectable bio‐nanocomposite hydrogel scaffolds. Journal of Applied Polymer Science 137 (2020) 48789. https://dx.doi.org/10.1002/app.48789 DOI: https://doi.org/10.1002/app.48789
[105] M. Ghorbani, L. Roshangar, J. Soleimani Rad. Development of reinforced chitosan/pectin scaffold by using the cellulose nanocrystals as nanofillers: An injectable hydrogel for tissue engineering. European Polymer Journal 130 (2020) 109697. https://dx.doi.org/10.1016/j.eurpolymj.2020.109697 DOI: https://doi.org/10.1016/j.eurpolymj.2020.109697
[106] R. Obregón, J. Ramón-Azcón, S. Ahadian. Nanofiber composites in blood vessel tissue engineering, in Nanofiber Composites for Biomedical Applications, M. Ramalingam, S. Ramakrishna, Ed(s)., Woodhead Publishing, Duxford, UK, 2017, p. 483-506. https://dx.doi.org/10.1016/B978-0-08-100173-8.00019-3 DOI: https://doi.org/10.1016/B978-0-08-100173-8.00019-3
[107] X. Zhang, Y. Xia, J. Xu, J. Kang, X. Li, Y. Li, W. Yan, F. Tian, B. Zhao, B. Li, C. Wang, L. Wang. Cell-free chitosan/silk fibroin/bioactive glass scaffolds with radial pore for in situ inductive regeneration of critical-size bone defects. Carbohydrate Polymers 332 (2024) 121945. https://dx.doi.org/10.1016/j.carbpol.2024.121945 DOI: https://doi.org/10.1016/j.carbpol.2024.121945
[108] X. Wang, Z. Ding, C. Wang, X. Chen, H. Xu, Q. Lu, D.L. Kaplan. Bioactive Silk Hydrogels with Tunable Mechanical Properties. Journal of Materials Chemistry B 6(2018) 2739-2746. https://dx.doi.org/10.1039/c8tb00607e DOI: https://doi.org/10.1039/C8TB00607E
[109] S. Yodmuang, S.L. McNamara, A.B. Nover, B.B. Mandal, M. Agarwal, T.A. Kelly, P.H. Chao, C. Hung, D.L. Kaplan, G. Vunjak-Novakovic. Silk microfiber-reinforced silk hydrogel composites for functional cartilage tissue repair. Acta Biomaterialia 11(2015) 27-36. https://dx.doi.org/10.1016/j.actbio.2014.09.032 DOI: https://doi.org/10.1016/j.actbio.2014.09.032
[110] X. Zhang, L. Xiao, Z. Ding, Q. Lu, D.L. Kaplan. Engineered Tough Silk Hydrogels through Assembling β-Sheet Rich Nanofibers Based on a Solvent Replacement Strategy. ACS Nano 16 (2022) 10209-10218. https://dx.doi.org/10.1021/acsnano.2c01616 DOI: https://doi.org/10.1021/acsnano.2c01616
[111] Z. Ding, M. Zhou, Z. Zhou, W. Zhang, X. Jiang, X. Lu, B. Zuo, Q. Lu, D.L. Kaplan. Injectable Silk Nanofiber Hydrogels for Sustained Release of Small-Molecule Drugs and Vascularization. ACS Biomaterials Science & Engineering 5 (2019) 4077-4088. https://dx.doi.org/10.1021/acsbiomaterials.9b00621 DOI: https://doi.org/10.1021/acsbiomaterials.9b00621
[112] K. Wang, W. Cheng, Z. Ding, G. Xu, X. Zheng, M. Li, G. Lu, Q. Lu. Injectable silk/hydroxyapatite nanocomposite hydrogels with vascularization capacity for bone regeneration. Journal of Materials Science & Technology 63 (2021) 172-181. https://dx.doi.org/10.1016/j.jmst.2020.02.030 DOI: https://doi.org/10.1016/j.jmst.2020.02.030
[113] S. Banijamali, M. Heydari, M. Mozafari. Cellular response to bioactive glasses and glass-ceramics, in Handbook of Biomaterials Biocompatibility, M. Mozafari, J. Rajadas, D.L. Kaplan, Ed(s)., Woodhead Publishing, Duxford, UK, 2020, p. 395-421. https://dx.doi.org/10.1016/B978-0-08-102967-1.00019-0 DOI: https://doi.org/10.1016/B978-0-08-102967-1.00019-0
[114] M. Raza, S. Zahid, A. Asif. Analytical tools for substituted hydroxyapatite, in Handbook of Ionic Substituted Hydroxyapatites, A. Khan, S. Saeed, I. Khan, Ed(s)., Woodhead Publishing, Duxford, UK, 2020, p. 21-51. https://dx.doi.org/10.1016/B978-0-08-102834-6.00002-1 DOI: https://doi.org/10.1016/B978-0-08-102834-6.00002-1
[115] U.U. Akobundu, I.H. Ifijen, P. Duru, J.C. Igboanugo, I. Ekanem, M. Fagbolade, A.S. Ajayi, M. George, B. Atoe, J.T. Matthews. Exploring the role of strontium-based nanoparticles in modulating bone regeneration and antimicrobial resistance: a public health perspective. RSC Advances 15 (2025) 10902-10957. https://dx.doi.org/10.1039/d5ra00308c DOI: https://doi.org/10.1039/D5RA00308C
[116] N. Zhang, D. Zhai, L. Chen, Z. Zou, K. Lin, J. Chang. Hydrothermal synthesis and characterization of Si and Sr co-substituted hydroxyapatite nanowires using strontium containing calcium silicate as precursors. Materials Science and Engineering: C 37 (2014) 286-291. https://dx.doi.org/10.1016/j.msec.2014.01.011 DOI: https://doi.org/10.1016/j.msec.2014.01.011
[117] F. Baldassarre, A. Altomare, E. Mesto, M. Lacalamita, B. Dida, A. Mele, E.M. Bauer, M. Puzone, E. Tempesta, D. Capelli, D. Siliqi, F. Capitelli. Structural Characterization of Low-Sr-Doped Hydroxyapatite Obtained by Solid-State Synthesis. Crystals 13 (2023) 117. https://dx.doi.org/10.3390/cryst13010117 DOI: https://doi.org/10.3390/cryst13010117
[118] L. Stipniece, A. Ramata-Stunda, J. Vecstaudza, I. Kreicberga, D. Livkisa, A. Rubina, A. Sceglovs, K. Salma-Ancane. A Comparative Study on Physicochemical Properties and In Vitro Biocompatibility of Sr-Substituted and Sr Ranelate-Loaded Hydroxyapatite Nanoparticles. ACS Applied Bio Materials 6 (2023) 5264-5281. https://dx.doi.org/10.1021/acsabm.3c00539 DOI: https://doi.org/10.1021/acsabm.3c00539
[119] X. Ding, X. Li, C. Li, M. Qi, Z. Zhang, X. Sun, L. Wang, Y. Zhou. Chitosan/Dextran Hydrogel Constructs Containing Strontium-Doped Hydroxyapatite with Enhanced Osteogenic Potential in Rat Cranium. ACS Biomaterials Science & Engineering 5 (2019) 4574-4586. https://dx.doi.org/10.1021/acsbiomaterials.9b00584 DOI: https://doi.org/10.1021/acsbiomaterials.9b00584
[120] J.J. Grant, S.C. Pillai, S. Hehir, M. McAfee, A. Breen. Biomedical Applications of Electrospun Graphene Oxide. ACS Biomaterials Science & Engineering 7 (2021) 1278-1301. https://dx.doi.org/10.1021/acsbiomaterials.0c01663 DOI: https://doi.org/10.1021/acsbiomaterials.0c01663
[121] J. Yi, G. Choe, J. Park, J.Y. Lee. Graphene oxide-incorporated hydrogels for biomedical applications. Polymer Journal 52 (2020) 823-837. https://dx.doi.org/10.1038/s41428-020-0350-9 DOI: https://doi.org/10.1038/s41428-020-0350-9
[122] Y. Piao, B. Chen. Synthesis and Mechanical Properties of Double Cross-linked Gelatin-Graphene Oxide Hydrogels. International Journal of Biological Macromolecules 101 (2017) 791-798. https://dx.doi.org/10.1016/j.ijbiomac.2017.03.155 DOI: https://doi.org/10.1016/j.ijbiomac.2017.03.155
[123] M.M.H. Rumon, S.D. Sarkar, M.M. Uddin, M.M. Alam, S.N. Karobi, A. Ayfar, M.S. Azam, C.K. Roy. Graphene oxide based crosslinker for simultaneous enhancement of mechanical toughness and self-healing capability of conventional hydrogels. RSC Advances 12 (2022) 7453-7463. https://dx.doi.org/10.1039/d2ra00122e DOI: https://doi.org/10.1039/D2RA00122E
[124] P.M. Purcea Lopes, D. Moldovan, R. Fechete, L. Mare, L. Barbu-Tudoran, N. Sechel, V. Popescu. Characterization of a Graphene Oxide-Reinforced Whey Hydrogel as an Eco-Friendly Absorbent for Food Packaging. Gels 9 (2023) 298. https://dx.doi.org/10.3390/gels9040298 DOI: https://doi.org/10.3390/gels9040298
[125] L.-B. Jiang, S.-L. Ding, W. Ding, D.-H. Su, F.-X. Zhang, T.-W. Zhang, X.-F. Yin, L. Xiao, Y.-L. Li, F.-L. Yuan. Injectable sericin based nanocomposite hydrogel for multi-modal imaging-guided immunomodulatory bone regeneration. Chemical Engineering Journal 418 (2021) 129323. https://dx.doi.org/10.1016/j.cej.2021.129323 DOI: https://doi.org/10.1016/j.cej.2021.129323
[126] S.J. Lee, H. Nah, D.N. Heo, K.-H. Kim, J.M. Seok, M. Heo, H.-J. Moon, D. Lee, J.S. Lee, S.Y. An. Induction of osteogenic differentiation in a rat calvarial bone defect model using an In situ forming graphene oxide incorporated glycol chitosan/oxidized hyaluronic acid injectable hydrogel. Carbon 168 (2020) 264-277. https://dx.doi.org/10.1016/j.carbon.2020.05.022 DOI: https://doi.org/10.1016/j.carbon.2020.05.022
[127] M. Babaluei, Y. Mojarab, F. Mottaghitalab, M. Farokhi. Injectable hydrogel based on silk fibroin/carboxymethyl cellulose/agarose containing polydopamine functionalized graphene oxide with conductivity, hemostasis, antibacterial, and anti-oxidant properties for full-thickness burn healing. International Journal of Biological Macromolecules 249 (2023) 126051. https://dx.doi.org/10.1016/j.ijbiomac.2023.126051 DOI: https://doi.org/10.1016/j.ijbiomac.2023.126051
[128] L. Wang, R. Lu, J. Hou, X. Nan, Y. Xia, Y. Guo, K. Meng, C. Xu, X. Wang, B. Zhao. Application of injectable silk fibroin/graphene oxide hydrogel combined with bone marrow mesenchymal stem cells in bone tissue engineering. Colloids and Surfaces A: Physicochemical and Engineering Aspects 604 (2020) 125318. https://dx.doi.org/10.1016/j.colsurfa.2020.125318 DOI: https://doi.org/10.1016/j.colsurfa.2020.125318
[129] D.N. Cespedes-Valenzuela, S. Sanchez-Renteria, J. Cifuentes, M. Gantiva-Diaz, J.A. Serna, L.H. Reyes, C. Ostos, C. Cifuentes-De la Portilla, C. Munoz-Camargo, J.C. Cruz. Preparation and Characterization of an Injectable and Photo-Responsive Chitosan Methacrylate/Graphene Oxide Hydrogel: Potential Applications in Bone Tissue Adhesion and Repair. Polymers 14 (2021) 126. https://dx.doi.org/10.3390/polym14010126 DOI: https://doi.org/10.3390/polym14010126
[130] N. Amiryaghoubi, N. Noroozi Pesyan, M. Fathi, Y. Omidi. Injectable thermosensitive hybrid hydrogel containing graphene oxide and chitosan as dental pulp stem cells scaffold for bone tissue engineering. International Journal of Biological Macromolecules 162 (2020) 1338-1357. https://dx.doi.org/10.1016/j.ijbiomac.2020.06.138 DOI: https://doi.org/10.1016/j.ijbiomac.2020.06.138
[131] K. Khodaverdi, S.M. Naghib, M.R. Mozafari, M. Rahmanian. Chitosan/hydroxyapatite hydrogels for localized drug delivery and tissue engineering: A review. Carbohydrate Polymer Technologies and Applications 9 (2025) 100640. https://dx.doi.org/10.1016/j.carpta.2024.100640 DOI: https://doi.org/10.1016/j.carpta.2024.100640
[132] M. Chen, Y. Wang, P. Yuan, L. Wang, X. Li, B. Lei. Multifunctional bioactive glass nanoparticles: surface-interface decoration and biomedical applications. Regenerative Biomaterials 11 (2024) rbae110. https://dx.doi.org/10.1093/rb/rbae110 DOI: https://doi.org/10.1093/rb/rbae110
[133] N. Jain, S. Tiwari. Biomedical application of carbon nanotubes (CNTs) in vulnerable parts of the body and its toxicity study: A state-of-the-art-review. Materials Today: Proceedings 46 (2021) 7608-7617. https://dx.doi.org/10.1016/j.matpr.2021.01.895 DOI: https://doi.org/10.1016/j.matpr.2021.01.895
[134] T. Won, M. Goh, C. Lim, J. Moon, K. Lee, J. Park, K. Chung, Y. Kim, S. Lee, H.J. Hong, K. Gwon. Recent Progress in Cellulose Nanofibril Hydrogels for Biomedical Applications. Polymers 17 (2025) 2272. https://dx.doi.org/10.3390/polym17172272 DOI: https://doi.org/10.3390/polym17172272
[135] A.N. Ghulam, O.A.L. dos Santos, L. Hazeem, B. Pizzorno Backx, M. Bououdina, S. Bellucci. Graphene Oxide (GO) Materials—Applications and Toxicity on Living Organisms and Environment. Journal of Functional Biomaterials 13 (2022) 77. https://dx.doi.org/10.3390/jfb13020077 DOI: https://doi.org/10.3390/jfb13020077
[136] E.A.M. Machado, A.C. da Silva Rocha, L.R. de Menezes. Applicability of Hydrogels as Platforms for Bone Regeneration: A Mini‐Review. Polymers for Advanced Technologies 36 (2025) e70336. https://dx.doi.org/10.1002/pat.70336 DOI: https://doi.org/10.1002/pat.70336
[137] M. Fernandes, M. Vieira, D. Peixoto, N.M. Alves. Nature-Based Hydrogels Combined with Nanoparticles for Bone Regeneration. Journal of Functional Biomaterials 16 (2025) 317. https://dx.doi.org/10.3390/jfb16090317 DOI: https://doi.org/10.3390/jfb16090317
[138] S. Palati, D. Ganapathy, S. Sekaran. Whitlockite as a next-generation biomaterial for bone regeneration: A systematic review of In Vivo evidence for bone regeneration. Journal of Oral Biology and Craniofacial Research 15 (2025) 1176-1182. https://dx.doi.org/10.1016/j.jobcr.2025.08.002 DOI: https://doi.org/10.1016/j.jobcr.2025.08.002
[139] H.M. El-Husseiny, E.A. Mady, L. Hamabe, A. Abugomaa, K. Shimada, T. Yoshida, T. Tanaka, A. Yokoi, M. Elbadawy, R. Tanaka. Smart/stimuli-responsive hydrogels: Cutting-edge platforms for tissue engineering and other biomedical applications. Materials Today Bio 13 (2022) 100186. https://dx.doi.org/10.1016/j.mtbio.2021.100186 DOI: https://doi.org/10.1016/j.mtbio.2021.100186
[140] L. Zhang, T. Zhao, M. Liu. Bioinspired Multiphase Gels Using Spatial Confinement Strategy. Accounts of Materials Research 5 (2024) 48-63. https://dx.doi.org/10.1021/accountsmr.3c00174 DOI: https://doi.org/10.1021/accountsmr.3c00174
[141] Ø. Øvrebø, G. Perale, J.P. Wojciechowski, C. Echalier, J.R.T. Jeffers, M.M. Stevens, H.J. Haugen, F. Rossi. Design and clinical application of injectable hydrogels for musculoskeletal therapy. Bioengineering & Translational Medicine 7 (2022) e10295. https://dx.doi.org/10.1002/btm2.10295. DOI: https://doi.org/10.1002/btm2.10295
[142] I. Negut, B. Bita. Exploring the Potential of Artificial Intelligence for Hydrogel Development-A Short Review. Gels 9 (2023) 845. https://dx.doi.org/10.3390/gels9110845 DOI: https://doi.org/10.3390/gels9110845
[143] Z. Li, P. Song, G. Li, Y. Han, X. Ren, L. Bai, J. Su. AI energized hydrogel design, optimization and application in biomedicine. Materials Today Bio 25 (2024) 101014. https://dx.doi.org/10.1016/j.mtbio.2024.101014 DOI: https://doi.org/10.1016/j.mtbio.2024.101014
[144] H. Liao, S. Hu, H. Yang, L. Wang, S. Tanaka, I. Takigawa, W. Li, H. Fan, J.P. Gong. Data-driven de novo design of super-adhesive hydrogels. Nature 644 (2025) 89-95. https://dx.doi.org/10.1038/s41586-025-09269-4 DOI: https://doi.org/10.1038/s41586-025-09269-4
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