Table 1 Summary of typical GelMA-based hydrogel scaffolds with various bioactive properties for accelerated bone regeneration
Categories | Components | Composite hydrogel scaffolds | Used cells lines | Cell seeding (2D or 3D) | Physical properties | Bioactivities | References | Year of publication |
|---|---|---|---|---|---|---|---|---|
GelMA-based bone scaffolds with osteoconductivity | Biological ceramics | GelMA-HAp-HAD/Col I | rBMSCs | 2D | Excellent swelling properties, mechanical stability and delayed degradation | Promoted the migration and differentiation of BMSCs, improved angiogenesis and bone regeneration | [15] | 2022 |
| Â | Â | GelMA-HAP-Sn | rBMSCs | 2D | Injection available, good mechanical, swelling and degradation properties | Promoted survival, proliferation and migration of cells, increased expression of osteogenic markers and matrix mineralization | [16] | 2021 |
| Â | Â | GelMA/nHAP/CSA | MC3T3-E1 | 2D | Improved material stability and compression property, favorable swelling property and degradation ability | Enhanced migration and osteogenic differentiation of osteoblasts, improved bone regeneration | [17] | 2023 |
| Â | Â | GelMA-HAMA/nHAP/USCEXOs | rBMSCs, EPCs | 2D | Satisfactory controlled release and suitable biomechanical properties | Promoted angiogenesis and osteogenesis, significantly accelerated bone repair | [18] | 2023 |
| Â | Â | GelMA/m-HANFs | MC3T3-E1, rBMSCs | 2D | Improved mechanical, swelling and degradation properties | Biocompatibility, accelerated bone regeneration | [19] | 2022 |
|  |  | GelMA/PCL/ β-TCP | rBMSCs, HUVEC, RAW264.7 Schwann cells | 2D | Porous structural and good mechanical support function | Biocompatibility, promoted tissue regeneration and reconstruction by improving blood vessel, improved bone remodeling | [20] | 2022 |
|  |  | GelMA/β-TCP/Alginate/MXene | rBMSCs, RAW264.7 | 3D | Good shear thinning properties and suitable viscosity, improved mechanical strength | Biocompatibility, excellent antibacterial properties, promoted healing of infected bone defects and bone regeneration | [21] | 2022 |
|  | Bioactive glass | BG-XLS/GelMA-DFO | MC3T3-E1, ADSCs | 2D | Suitable pore structure and degradability, improved mechanical properties | Promoted osteogenic differentiation of ADSCs, increased expression of HIF-1α and VEGF on ADSCs, promoted regeneration of bone defects | [22] | 2021 |
| Â | BG-GelMA | mBMSCs | 2D | Increased compression modulus and mineralization, good swelling behavior and degradation rate | Promoted cell adhesion, proliferation and osteogenic differentiation | [23] | 2018 | |
| Â | Biomimetic composite hydrogel | GelMA-BMSCs | BMSCs | 3D | Injectability and porous structure | Good cytocompatibility and proliferative properties, promoted new bone formation and angiogenesis | [24] | 2021 |
| Â | GelMA-RF | KUSA-A1 | 3D | Delayed photocrosslink curing and suitable mechanical function | Increased cell viability, promoted differentiation and maturation of osteoblasts | [25] | 2021 | |
| Â | GelMA-BMSCs/PLA-PGA-PLA-ECs | BMSCs, RAOECs | 3D | Sufficient mechanical properties and good permeability | Increased cell viability, promoted differentiation and maturation of osteoblasts | [26] | 2022 | |
| Â | GelMA/HAMA/Alginate/GO | BMSCs, BMMs | 3D | Stable porous structure, suitable mechanical, swelling and degradation properties | Promoted polarization of BMMS to M2 type, promoted osteogenic differentiation of BMSCs, improved osteogenic repair | [27] | 2022 | |
GelMA-based vascularized bone scaffolds | Bioactive cytokines | GelMA/HAMA/DBM/VEGF | BMSCs | 3D | High mechanical strength, appropriate biodegradation rate and controllable VEGF release | Biocompatibility, excellent ectopic bone regeneration ability, successful repair of a 15Â mm long tibial defect in a rabbit | [28] | 2021 |
| Â | Eth-DFO@GelMA/GGMA | BMSCs, HUVECs | 3D | Stable grid-like structure, improved printability and mechanical property, slow release of DFO | Promoted migration and tube formation of ECs, improved osteogenesis and angiogenesis | [29] | 2022 | |
| Â | vECM-GelMA | BMSCs, HUVECs | 2D | High BMP-2 loading efficiency, slow release of BMP-2 | Promoted formation and vascularization of new bone | [30] | 2022 | |
| Â | CPP-L/GelMA | MC3T3-E1 RAW264.7 HUVECs | 2D | Durative release of internal functional components, suitable mechanical function | Promoted angiogenesis and osteogenesis, ROS scavenging ability, inhibit osteoclast differentiation | [31] | 2023 | |
| Â | GelMA/OMP | hMSCs | 3D | Enhanced mechanical properties, prolonged oxygen release | Good cytocompatibility, promoted osteogenic differentiation and angiogenesis | [32] | 2023 | |
| Â | Bioactive inorganic ions | GelMA-BPa-Mg | rBMSCs, HUVECs | 3D | Injection available, slow release of BP and Mg2+ | Good tube formation, high expression of e-NOS and VEGF, reduction of TRAP-positive multinucleated osteoclasts, improved osteogenesis and angiogenesis | [33] | 2021 |
| Â | GelMA/Li-MBG | BMSCs, RAW264.7 HUVECs | 2D | Good mechanical properties, continuous Li+ release | Promoted cell proliferation, angiogenesis, osteogenesis and regulation of macrophages in a high-glucose microenvironment, reduction of M1 macrophages | [34] | 2022 | |
| Â | GelMA-PEGDA/SiPAC | BMSCs, HUVECs | 2D | Good biodegradability, slow release of silicon and phosphorus ions | Satisfactory biocompatibility promoted bone regeneration and vascularization | [35] | 2022 | |
| Â | DFO/MnCO@GelMA | RAW264.7 HUVECs MSCs | 2D | Good surface hydrophilicity and mechanical support, the stent is responsive to H2O2 and continuously releases CO | Good cytocompatibility, reduced M1 polarization of the macrophages, improved angiogenesis and osteogenesis | [36] | 2022 | |
| Â | GelMA/GeP@Cu | BMSCs HUVECs NSCs, PC12 | 2D | Enhanced conductivity, good mechanical properties and suitable swelling behavior | Good antibacterial properties, promoted osteogenic and angiogenic properties, stimulate neurite growth and neural differentiation | [37] | 2023 | |
| Â | Vascularized biomimetic periosteum | pODM/GelMA | BMSCs MC3T3-E1 | 2D | Good adhesion and proliferation properties | Concentration-dependent chemotaxis towards BMSCs, promoted bone repair of segmental bone defects in rabbit radius | [38] | 2020 |
| Â | CaPs@GelMA-F | MC3T3-E1, HUVECs | 2D | Good mechanical properties, continuous release of calcium ions | Good biocompatibility, promoted mineralization, osteogenesis and angiogenesis | [39] | 2020 | |
|  | GelMA-BPb@Mg/GelMA-PEG-β-TCP | BMSCs, HUVECs, NSCs, PC12 | 2D | Suitable mechanical properties and swelling behavior | Induction of angiogenesis and peripheral nerve repair, promoted bone regeneration | [40] | 2022 | |
GelMA-based bone scaffolds with osteoinductivity | Growth factors and their substitutes | GelMA/BMPs | BMSCs, RAW264.7 | 3D | Enhanced mechanical properties, sustained release of BMP-4 | Biocompatibility, significant increase in BMP-2 expression, induced M2 macrophage polarization and improved inflammatory microenvironment, accelerated bone repair | [41] | 2020 |
| Â | GelMA/PTHrp | MC3T3-E1 | 2D | Effective in prolonging the release of abaloparatide | Promoted viability, differentiation and mineralization of preosteoblasts, accelerated bone regeneration | [42] | 2019 | |
| Â | GelMA/OGP | MC3T3-E1 | 2D | Slow and sustained release of OGP, good mechanical properties | Promoted bone regeneration | [43] | 2020 | |
| Â | GelMA-KP/QK | BMSCs, HUVECs | 2D | Self-healing and injectable properties, slow release of KP/QK | Improved osteogenesis and angiogenesis | [44] | 2022 | |
| Â | Bioactive metal ions | GelMA/ZIF-8 | rBMSCs | 2D | Suitable mechanical properties and swelling behavior, continuous release of Zn2+ | Good cytocompatibility, significantly enhanced expression level of ALP, effective antimicrobial activity, improved alveolar bone regeneration | [45] | 2022 |
| Â | GelMA/Sr-MBGNs | TIID BMSCs Raw 264.7 | 2D | Enhanced mechanical properties and mineralization, suitable swelling and degradation properties | Increased the level of OCN (NCPs), regulated alignment of hyaluronan on intralaminar mineralization and promotes osteoblast differentiation via Kindlin-2/PTH1R/ OCN axis | [46] | 2023 | |
| Â | Ce@GelMA | rBMSCs | 2D | Significantly enhanced mechanical properties, rapid capture of detrimental ROS | Good cytocompatibility, promoted bone regeneration | [47] | 2022 | |
| Â | Gd-MoS2-NAGA/GelMA | ROBs | 2D | Excellent photothermal ability, slow release of Gd3+ | Good cytocompatibility, excellent antimicrobial and antitumor properties, promoted new bone formation | [48] | 2023 | |
| Â | Two-dimensional nanomaterials | GelMA/SiGO | hMSCs | 3D | Enhanced production, retention and bioactivity of BMPs | Improved mineralization and accelerated bone repair | [49] | 2021 |
| Â | Â | GelMA/HAMA/Alginate/GO | BMSCs, BMMs | 3D | Stable porous structure, suitable mechanical, swelling and degradation properties | Promoted polarization of BMMs to M2 type, promoted osteogenic differentiation of BMSCs, improved osteogenic repair | [27] | 2022 |
| Â | Â | GelMA/BPb@Mg | BMSCs, SCs, PC12 | 2D | Improved mechanical properties, suitable photothermal properties | High antibacterial activity, improved local inflammatory microenvironment, promoted regeneration of bone and CGRP nerve fibers | [50] | 2023 |
| Â | Â | GelMA/CNT | NIH-3T3, hMSCs | 3D | Improved mechanical properties | Good cytocompatibility | [51] | 2012 |
| Â | Â | GelMA/TiO2 | hBMSCs, BMMs, RAW 264.7 | 2D | Well preserved nanotubular morphology, slow release of Mg2+ | Exhibited favorable effects on growth rate and bone formation capacity | [52] | 2019 |
| Â | Â | GelMA/HNT | hDPSCs | 2D | Good mechanical, swelling and degradation properties | Good cytocompatibility, accelerated bone formation | [53] | 2019 |
3D-bioprinted GelMA-based bone scaffolds |  | GelMA/β-TCP/Alginate/MXene | rBMSCs, RAW264.7 | 3D | Good shear thinning properties and suitable viscosity, improved mechanical strength, | Biocompatibility, excellent antibacterial properties, promoted healing of infected bone defects and bone regeneration | [21] | 2022 |
| Â | Â | GelMA-BMSCs/PLA-PGA-PLA-ECs | BMSCs, RAOECs | 3D | Sufficient mechanical properties and good permeability | Exhibited a coupling effect between angiogenesis and osteogenesis, in situ vascularization, effectively promoted new bone formation | [26] | 2022 |
| Â | Â | GelMA-Alg-HUVECs/ GelMA-Alg-WH/HAP-hMSCs | HUVECs, hMSCs | 3D | Good mechanical, swelling, degradability properties | Good cytocompatibility and excellent osteogenic properties | [54] | 2023 |
| Â | Â | GelMA-PEGDA/SiPAC | BMSCs, HUVECs | 2D | Good biodegradability, slow release of silicon and phosphorus ions | Satisfactory biocompatibility, promoted bone regeneration and vascularization | [35] | 2022 |
| Â | Â | Eth-DFO@GelMA/GGMA | BMSCs, HUVECs | 3D | Stable grid-like structure, improved printability and mechanical property, slow release of DFO | Promoted migration and tube formation of ECs, improved osteogenesis and angiogenesis | [29] | 2022 |
| Â | Â | GelMA/HA-Ce | MC3T3-E1 | 3D | Significantly enhanced mechanical properties, exhibited a uniformly porous microstructure | Good cytocompatibility, promoted bone regeneration | [55] | 2022 |
| Â | Â | GelMA-BMSCs/Dextran emulsion | rBMSCs | 3D | Porous structure, good mechanical and degradation properties | Promoted cell proliferation, migration, spreading and osteogenic differentiation of rBMSCs via regulation of YAP signal pathway, improved bone healing | [56] | 2022 |
| Â | Â | GelMA/BPs | Cells from the BPs | 3D | Strong shear thinning behavior and high gel strength | Improved osteogenesis | [57] | 2020 |
| Â | Â | GelMA/Alg/C3S | hADSCs | 2D | Good printability, improved mechanical properties | Satisfactory cytocompatibility and osteogenic capacity | [58] | 2023 |
| Â | Â | GelMA/CQDs | hBMSCs, hECs RAW264.7 | 2D | Excellent printability and photothermal properties | Anti-inflammatory activity, promoted osteogenic and angiogenesis, NIR-triggered anti-osteosarcoma performance and vascularized bone regeneration | [59] | 2023 |
| Â | Â | GelMA-PPy-Fe | hBMSCs RAW264.7 | 3D | Excellent shape fidelity, enhanced conductivity | Good cytocompatibility and improved osteogenic differentiation | [60] | 2023 |