Engineered Hydrogels for Musculoskeletal Regeneration: Advanced Synthesis Strategies and Therapeutic Efficacy in Preclinical Models
Abstract
1. Introduction
2. Materials and Methods
3. Novel Design for Functionalized Composite Hydrogels
4. Therapeutic Outcomes in Musculoskeletal Models
5. Therapeutic Applications and Clinical Translation
6. Conclusions
Author Contributions
Funding
Data Availability Statement
Conflicts of Interest
References
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Gel Composition | Crosslinking Mechanism | Functionalization | Mechanical Properties | Application | Reference |
---|---|---|---|---|---|
GelMA with Mg2+-modified black phosphorus nanosheets (GelMA-BP@Mg). | Chemical | Neurovascularization agents | Compressive modulus ~150 kPa | Bone regeneration | [31] |
Hydrogel microspheres composed of methacrylate-modified sulfonated azocalix [4] arene (SAC4A-MA), methacrylated hyaluronic acid (HA-MA), and MMP-13-sensitive peptide crosslinkers; loaded with hydroxychloroquine via host–guest interactions. | Enzymatic | Hypoxia-responsive elements | Compressive modulus ~60 kPa | Osteoarthritis treatment | [32] |
Self-healing injectable hydrogel (Cur&Mg-QCS/PF) composed of quaternized chitosan (QCS), poloxamer F127 (PF), loaded with Mg2+ and curcumin. | Chemical | Anti-inflammatory agents | Tensile strength ~800 kPa | Tendon-to-bone healing | [33] |
Injectable hydrogel composed of methacrylated silk fibroin as the base material, mixed with platelet-rich plasma, and embedded with silk fibroin microspheres that contain the bioactive compound berberine. The gel is photocrosslinked in situ using ultraviolet light. | Physical/Chemical | Inflammatory-responsive agents | Compressive modulus ~120 kPa | Bone tissue engineering | [34] |
Hybrid injectable biomimetic hydrogel synthesized by incorporating laponite (LP) and calcium phosphate cement (CPC) into gelatin via a one-step method. The resulting composite is referred to as LC hydrogel. | Adaptive degradation | Tissue healing synchronization | Compressive modulus ~100 kPa | Bone regeneration | [35] |
Hydrogel microspheres were fabricated using light-induced crosslinking of GelMA via a microfluidic system to support adhesion and proliferation of bone marrow mesenchymal stem cells (BMSCs). | Physical | Cell encapsulation | Diameter 50–200 µm | Musculoskeletal regeneration | [36] |
GelMA combined with oxidized chondroitin sulfate (OCS), where OCS provides aldehyde groups forming Schiff base bonds with GelMA to enhance mechanical strength and support cartilage regeneration. | Chemical | Cartilage regeneration | Compressive modulus ~80 kPa | Cartilage repair | [37] |
Hydrogel | Experimental Model | Therapeutic Results | Reference |
---|---|---|---|
RGD-Heparin-MMP-degradable HyA | Rat TA (VML) | Functional recovery, neovascularization, myofiber ingrowth | [49] |
Stiffness-tuned HyA (1.1–10.6 kPa) | Rat LD (VML) | Max force restoration (optimal at 3 kPa), reduced inflammation | [50] |
Magnetic alginate + Fe3O4 nanoparticles | Mouse TA (VML) | Improved muscle force, volume, CSA via magnetic stimulation | [51] |
PEG hydrogel + laminin peptide | Mouse muscle injury | Pro-regenerative macrophage polarization, improved fiber organization | [52] |
ROS-scavenging gelatin-PEG hydrogel | Mouse VML | Increased Pax7, MyoD, reduced oxidative stress, enhanced regeneration | [53] |
PEG hydrogel with IGF-1 + HGF | Rat VML | Greater force recovery, enhanced fiber size, angiogenesis | [54] |
GelMA hydrogel + MSCs + PDGF | Mouse muscle defect | MSC engraftment, angiogenesis, increased functional recovery | [55] |
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Calin, G.; Costescu, M.; Nour, M.; Ciuhodaru, T.; Denisa, B.-M.; Duceac, L.D.; Mihai, C.; Munteanu, M.F.; Trifunschi, S.; Oancea, A.; et al. Engineered Hydrogels for Musculoskeletal Regeneration: Advanced Synthesis Strategies and Therapeutic Efficacy in Preclinical Models. Polymers 2025, 17, 2094. https://doi.org/10.3390/polym17152094
Calin G, Costescu M, Nour M, Ciuhodaru T, Denisa B-M, Duceac LD, Mihai C, Munteanu MF, Trifunschi S, Oancea A, et al. Engineered Hydrogels for Musculoskeletal Regeneration: Advanced Synthesis Strategies and Therapeutic Efficacy in Preclinical Models. Polymers. 2025; 17(15):2094. https://doi.org/10.3390/polym17152094
Chicago/Turabian StyleCalin, Gabriela, Mihnea Costescu, Marcela Nour (Cârlig), Tudor Ciuhodaru, Batîr-Marin Denisa, Letitia Doina Duceac, Cozmin Mihai, Melania Florina Munteanu, Svetlana Trifunschi, Alexandru Oancea, and et al. 2025. "Engineered Hydrogels for Musculoskeletal Regeneration: Advanced Synthesis Strategies and Therapeutic Efficacy in Preclinical Models" Polymers 17, no. 15: 2094. https://doi.org/10.3390/polym17152094
APA StyleCalin, G., Costescu, M., Nour, M., Ciuhodaru, T., Denisa, B.-M., Duceac, L. D., Mihai, C., Munteanu, M. F., Trifunschi, S., Oancea, A., & Damir, D. L. (2025). Engineered Hydrogels for Musculoskeletal Regeneration: Advanced Synthesis Strategies and Therapeutic Efficacy in Preclinical Models. Polymers, 17(15), 2094. https://doi.org/10.3390/polym17152094