Polydopamine Nanocomposite Hydrogel for Drug Slow-Release in Bone Defect Repair: A Review of Research Advances
Abstract
1. Introduction
2. Application and Function of PDA in Bone Defect Repair
2.1. Anti-Inflammation
2.2. Promoting Cell Adhesion and Proliferation
2.3. Promoting Osteogenesis and Angiogenesis
3. Advances in the Application of PDA-Hydrogel Based Drug Slow Release System in the Repair of Bone Defects
3.1. Composite Nanohydrogels of Natural Materials with Polydopamine Nanostructures
3.1.1. Chitosan-Based PDA Hydrogel
3.1.2. Alginate-Based PDA Hydrogel
3.1.3. Gelatin-Based PDA Hydrogel
3.2. Composite Nanohydrogels of Synthetic Materials with Polydopamine Nanostructures
3.2.1. Nanohydrogels Based on Frequently Studied Synthetic Materials
3.2.2. Nanohydrogels Based on Self-Assembling Peptides
4. Conclusions and Outlook
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Acknowledgments
Conflicts of Interest
References
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Type of Composite Hydrogel | Types of Cells/Bacteria | Type of Animal Model | Drugs/Growth Factors/Others | Advantages | Disadvantages | Reference |
---|---|---|---|---|---|---|
PDA/Hydroxybutyl chitosan hydrogel | hBMMSCs | SD rats | Aspirin | Dual responsive properties | Complex processing | Wan et al. [82] |
PDA/alginate hydrogel | BMSCs | / | Silver Nanoparticles | Antibacterial/anti-infective properties | Insufficient mechanical strength | Zhang et al. [83] |
PDA/Alginate-allylated double-cross-linked hydrogels | MG63 rBMSCs | / | DOX | Fast kinetic response/High UV cross-linking conversion efficiency/Excellent mechanical properties | Insufficient stability of drug release | Chen et al. [84] |
GelMA-PDA/HA hydrogel | BMSCs | New Zealand white rabbits | BMP-2 TGF-β3 | Excellent osteochondral repair | Reducing degradation speed | Gan et al. [85] |
GelMA/PMMA/PDA hydrogel | BMSCs | BALB/c rats | / | Good biocompatibility/degradation properties | Local overheating | Wu et al. [86] |
PLGA-PDA-/Alginate-RGD hydrogel | BMSCs HUVECs HELA MC3T3-E1 | Fischer 344 rats SD rats | BMP-2 VEGF BP Doxorubicin Hydrochloride | Precise and timely drug release | Complex processing | Dashtimoghaamet al. [87] |
Polyvinyl alcohol (PVA)/PDA@HAP hydrogel | BMSCs | SD rats | Silver NanoparticlesHAP | Long-lasting antimicrobial effect | Induction of cytotoxicity by silver nanoparticles | Li et al. [88] |
PDA/Hyaluronic acid methacrylate hydrogel MPs | BMSCs | SD rats Rabbits | Barium titanate nanoparticles Stem cell recruitment peptides | Precise electrical stimulation | Poor stability | Han et al. [89] |
PDA hydrogel | hBMSCs | SD rats | CNT PLA | High mechanical strength | Large manufacturing scale | Sun et al. [90] |
PDA@E2/HA/GelMA/Gel hydrogel | BMSCs | / | Employing estradiol BMSCs | Adaptation of complex defects | Degradation rate/trigger conditions need to be optimized | Chen et al. [91] |
MSN@pDA/Chitosan (CS) hydrogel | SMSCs | SD rats Rabbits | TGF-β3 IGF-I PDGF-BB | Activation of endogenous cartilage repair | Insufficient stability | Li et al. [92] |
PDA/Gelatin methacrylate/sodium alginate methacrylate (GA) hybrid hydrogel | HUVECs MC3T3-E1 | SD rats | DFO PO43− | Improving the microenvironment of bone regeneration | Insufficient biocompatibility/photothermal efficiency | Wu et al. [93] |
PDA/Hydroxypropyl chitosan/Gelatin (HG) hydrogel | HUVECs MC3T3-E1 | BALB/c rats | aFGF Ti3C2Tx Mxene nanosheets | Accelerating critical bone defect healing | Inadequate biosecurity/limited demand for light control devices | Wu et al. [94] |
KGN@PDA/UPy hydrogel | BMSCs | Rabbits | KGN miRNA@CaP NPs | Stable mechanical properties/strong self-healing ability | Complex forming process/insufficient transfection efficiency | Kang et al. [95] |
PDA/ PEEK/Gelatin hydrogel | hMSCs | / | BMP-2 | Enhanced osteogenic differentiation./Improved bio-inertness of the material | Limited drug loading | Zhang et al. [96] |
PDA/Fpolyacrylamide/Silk fibroin hydrogel | BMSCs HUVECs | SD rats | BMP-2DFO | Excellent interfacial adhesion/structural toughness/mechanical stiffness. | Need for multiple photothermal interventions, large implants to trigger foreign body reactions | Li et al. [97] |
BML@β-TCP/PDA carboxymethyl chitosan hydrogel | MC3T3-E1 | SD rats | BML-284 | Multipurpose bone repair | High preparation costs | Wu et al. [98] |
GPEGD/PDA hydrogel | MC3T3-E1 | SD rats | BMP-2 Heparin | Excellent mechanical properties/biocompatibility | Limited cell infiltration/Insufficient stability of ROS scavengers | Wu et al. [99] |
PDA@zeolitic imidazolate framework-8/Soft matrix hydrogel | MC3T3-E1 RAW264.7 HUVECs | SD rats | Zn2+ | Good structural stability/mechanical support | The complex diabetic microenvironment impairs the therapeutic effect | Wu et al. [100] |
PDA/Al/GP/Fibrin hydrogels | EMSCs | SD rats | Al GP | Dual functions of osteoinduction and immunomodulation | Alendronate affects the balance of bone remodeling | Shi et al. [101] |
Methacrylated silk fibroin (SFMA)/PDA hydrogel | HUVECs BMSCs | SD rats | MAP | Exhibits good biocompatibility/physicochemical properties | Uneven distribution of photothermal agent/local overheating | Ma et al. [102] |
Alginate methacrylate/Alginate/PDA hydrogel | MC3T3-E1 | SD rats | Ti3C2 MXene nanosheets | Good biocompatibility/osteogenic activity/immune-regulatory functions | Phototherapy produces free radicals that damage cells | Wu et al. [103] |
PDA/Polysaccharide chitin hydrogel | MC3T3-E1 BMSCs | Wistar male rats | Cu2+ Nano HAP | High biocompatibility/Significant osteogenic activity. | Insufficient interfacial bonding strength | Huang et al. [104] |
PDA/Polyethylene hydrogel (PEG) | MC3T3-E1 | SD rats | AgNPs | Mineralization/anti-infection dual function | Reducing the elasticity of hydrogel | Xu et al. [105] |
PDA/Chitosan/Gelatin hydrogel | HUVECs MC3T3-E1 RAW 264.7 | SD rats | Hydroxyapatite BaTiO3 NPs | Excellent immunomodulation/angiogenesis/osteogenesis/suitable for combat wound repair | Complex material processing | Wu et al. [106] |
PDACS/PCL/Hydrogel | HUVECs WJMSCs | / | HUVECs WJMSCs | Synergized to promote osteogenesis/vascularization | Calcium silicate degradation products affect pH/limited microstructure control | Chen et al. [107] |
Oxidized sodium alginate (OSA)/Gelatin (Gel)/PDA-nHA hydrogel | BMSCs | Japanese big-ear white rabbits | nHA | Injectable/easy to operate | Long-term stability of nano-hydroxyapatite (nHA) in vivo is insufficient | Liu et al. [108] |
CGH/PDA@HAP hydrogel | BMSCs | SD rats | Gallic acid Hydroxyapatite | Enhanced antibacterial and osteogenic synergy | Generation of acidic degradation products | Pang et al. [109] |
Characterization of the fucoidan/PDA hydrogel | PDLSCs | / | / | Enhanced osteogenic potential | Quality control of fucoidan sulfate was low | Kwack et al. [110] |
Polyacrylamide/PDA hydrogel | MG-63 | / | / | Matrix stiffness targets osteosarcoma cell apoptosis | Stiffness parameters need to be highly precise/difficult to adjust in clinical application | Deng et al. [111] |
Xanthan gum-PDA hydrogel | BMSCs | SD rats | SDF-1α Mg2+ | Excellent injectability/mechanical properties | High SDF-1α inactivation | Li et al. [28] |
OSA-GelDA@ACP/DA/Ag hydrogel | / | / | ACP DA Ag+ | Composite hydrogel combines tissue adhesion and anti-infection functions | The hydrogel flexibility/bond strength decreased | Zhong et al. [112] |
PDA/Chondroitin sulfate hydrogel | rBMSCs | New Zealand rabbits | SDF-1α | Sustained-release SDF-1α | Lack of control over release kinetics | Wu et al. [113] |
ALG/GelAGE-PDA@DOX hydrogels | rBMSCs MG 63 | / | Sr2+ DOX | Synergistic effect of chemotherapy and photothermal therapy (PTT) | Degree of cross-linking affects the stability of drug release | Chen et al. [84] |
PDA/GMS/Osteogenic hydrogel | P. gingivalis | SD rats | Amino antibacterial nanoparticle Magnetic nanoparticles | Precision antimicrobial therapy | Magnetic field conditioning devices limit clinical applications | Zhou et al. [114] |
PDA/Nano-hydroxyapatite (nHAP) hydrogel | MC3T3-E1 | / | PEEK Aspirin | Good biocompatibility/compressive strength/modulus | Poor cell adhesion to the inert surface of PEEK | Li et al. [115] |
CS/PDA hydrogel | HUVECs | / | DFO | Enhanced bond strength/angiogenic effect | Short half-life of deferoxamine/frequent injections required | Liu et al. [116] |
BNP-PEDOT-PSF-AG hydrogel | PDLSCs | SD rats | Bovine serum albumin nanoparticles Hydrogen sulfide | Promoting alveolar bone regeneration/reversing inflammatory microenvironment under diabetic conditions | Difficulty in controlling the release of H2S gas | Fang et al. [117] |
Alginate/TOCNF/PDA hydrogel | MC3T3-E1 | / | TOCNFs PDANPs | High osteogenic activity | Low structural fidelity after printing | Im et al. [118] |
GO-PHA-CPs hydrogel | MC3T3-E1 | SD rats | CPs | Exhibits excellent injectability/adhesion/antioxidant activity/osteoinductive properties | Limited self-repair capacity/degradation rate mismatch with bone formation rate | Ma et al. [119] |
DA-nano-hydroxyapatite hydrogel | 4T1 BMSCs | BALB/c mice | DDP | Synergistic photothermal anti-tumor/bone regeneration capabilities | Photothermal agents are potentially toxic | Luo et al. [120] |
MCG-HG-PLGA-PD-B hydrogel | ATDC5 MC3T3-E1 | / | BMP-7 | Promoting Structural Bionicity in Cartilage Regeneration | Insufficient scaffold porosity connectivity | Jung et al. [121] |
Gellan gum/PDA hydrogel | MC3T3-E1 | / | ALP | Polydopamine enhances the efficiency of mineralization | Increased material brittleness/complex preparation process | Douglas et al. [122] |
PF-127/HAMA/M@S (PH/M@S) hydrogel | rBMSCs HUVEC RAW264.7 | Mice | M@S NPs | Cost-effective/easy to synthesize/possesses multiple therapeutic capabilities | Nanoparticles prone to leakage | Liu et al. [123] |
PDA/LC hydrogel | BMSCs E. coli S. aureus | SD rats | / | Excellent osteogenic activity/angiogenic capacity/antimicrobial effects | Chitosan causes allergic reactions/complex preparation | Li et al. [124] |
Gel-PHA hydrogel | MC3T3-E1 | SD rats | nHA | Enhanced mechanical and osteogenic properties of gelatin hydrogels | Reduced hydrogel elasticity | Ma et al. [125] |
T/DOP-IL 4/CG-RGD hydrogel | BMSCs | / | IL-4 RGD peptide | IL-4 and RGD synergistically regulate the osteoimmune microenvironment | IL-4 short half-life/RGD overexpression | Li et al. [126] |
PDA/Gel-PAA hydrogel | BMSCs | New Zealand rabbits | TGF-β3 | Enhances the toughness and cell affinity of PAA hydrogels | Catechol oxidative cross-linking is irreversible/affects controllability of degradation | Yan et al. [127] |
AD/CS/RSF/EXO hydrogel | BMSCs | SD rats | Exosomes | Excellent mechanical properties/biodegradability/biocompatibility/the ability | Low efficiency in exosome extraction and loading | Zhang et al. [128] |
CTP-SA/TiO2@PDA hydrogel | HUVEC BMSCs Staphylococcus aureus Escherichia coli Streptococcus mutans | SD rats | Cu2O TiO2 NPs | Enhanced antimicrobial activity | Insufficient mechanical properties | Xu et al. [129] |
PDA@SiO2-PRF hydrogel | BMSCs | SD rats | PRF | Multi-level regulation of microenvironment | Proteins are prone to degradation/short shelf life | Ren et al. [130] |
Chitosan/ Polydopamine/NO-PVA hydrogel | MRSA MC3T3-E1 | SD rats | Ti-RP/PCP/RSNO NO | With combined photothermal/immunotherapy | Photothermal effect damages surrounding healthy tissue | Li et al. [131] |
PnP-iPRF hydrogel | BMSCs RAW 264.7 | Rats | i-PRF | Multiple pathways regulate the microenvironment | Immunogenic risk has not been completely ruled out | Li et al. [132] |
SP@MX/GelMA hydrogel | MG-63 MC3T3-E1 | Kunming mice | Tobramycin | Significantly enhances the initial adhesion and proliferation of cells | MXene nanosheets trigger inflammation | Yin et al. [133] |
Gelatin-Silkfibroin-Oxidized dextran/PLLA-PLGA-PCL/PDA hydrogel | BMSCs | SD rats | Kartogenin P24 peptides | Excellent cell compatibility/Dual-layer scaffolds synergistically repair osteochondral defects | Weak interfacial bonding strength between the two layers | Zheng et al. [134] |
SFO-TA-BGNF-PDA hydrogel | MG-63 | / | Bioactive glass | Integrated antimicrobial activity/antiosteosarcoma properties/osteoinduction of multiple functions | Aerogel has low mechanical strength and is not suitable for load-bearing applications | Abie et al. [135] |
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Li, X.; Tang, J.; Guo, W.; Dong, X.; Cao, K.; Tang, F. Polydopamine Nanocomposite Hydrogel for Drug Slow-Release in Bone Defect Repair: A Review of Research Advances. Gels 2025, 11, 190. https://doi.org/10.3390/gels11030190
Li X, Tang J, Guo W, Dong X, Cao K, Tang F. Polydopamine Nanocomposite Hydrogel for Drug Slow-Release in Bone Defect Repair: A Review of Research Advances. Gels. 2025; 11(3):190. https://doi.org/10.3390/gels11030190
Chicago/Turabian StyleLi, Xiaoman, Jianhua Tang, Weiwei Guo, Xuan Dong, Kaisen Cao, and Fushan Tang. 2025. "Polydopamine Nanocomposite Hydrogel for Drug Slow-Release in Bone Defect Repair: A Review of Research Advances" Gels 11, no. 3: 190. https://doi.org/10.3390/gels11030190
APA StyleLi, X., Tang, J., Guo, W., Dong, X., Cao, K., & Tang, F. (2025). Polydopamine Nanocomposite Hydrogel for Drug Slow-Release in Bone Defect Repair: A Review of Research Advances. Gels, 11(3), 190. https://doi.org/10.3390/gels11030190