Biomaterials Translational ›› 2024, Vol. 5 ›› Issue (3): 274-299.doi: 10.12336/biomatertransl.2024.03.005
• REVIEW • Previous Articles Next Articles
Shuhao Yang1,2, Haoming Wu5, Chao Peng3, Jian He6, Zhengguang Pu3, Zhidong Lin7, Jun Wang1,2, Yingkun Hu1,2, Qiao Su8, Bingnan Zhou9, Xin Yong10, Hai Lan3,*(), Ning Hu1,2,*(
), Xulin Hu3,4,*(
)
Received:
2024-07-10
Revised:
2024-08-22
Accepted:
2024-09-13
Online:
2024-09-28
Published:
2024-09-28
Contact:
Hai Lan,Ning Hu,Xulin Hu
E-mail:13714777@qq.com;huncqjoint@yeah.net;huxulin1993@163.com
About author:
Hai Lan, 13714777@qq.com.#Author equally.
Yang, S.; Wu, H.; Peng, C.; He, J.; Pu, Z.; Lin, Z.; Wang, J.; Hu, Y.; Su, Q.; Zhou, B.; Yong, X.; Lan H.; Hu, N.; Hu, X. From the microspheres to scaffolds: advances in polymer microsphere scaffolds for bone regeneration applications. Biomater Transl. 2024, 5(3), 274-299.
Figure 1. Construction of different types of bone repair scaffolds by screening the preparation method, materials and performance requirements of polymer microspheres. Different types of polymer microspheres can be obtained by different materials and preparation methods, mainly including solid microspheres, porous microspheres, core-shell microspheres, Janus microspheres and hollow microspheres, and polymer microspheres show good degradation behaviour, porous structure and good biocompatibility. Finally, the polymer microspheres were assembled into sintered, injectable, and incorporated microsphere scaffolds to exhibit different properties. Created with BioRender.com. PLA: poly(lactic acid); PLGA: poly(lactic-co-glycolic acid).
Figure 2. Coordination of various cells and molecules during bone regeneration. (A) Bones are composed of cortical bone and cancellous bone. Cortical osteons are called Haversian systems, with the Haversian canals in the center, containing blood vessels and nerves. (B) The cellular components of bone tissue are osteoprogenitor cells, osteoblasts, osteocytes, and osteoclasts. (C) Bone regeneration process can be divided into three stages: inflammation, bone formation, and bone remodelling. (D) Bone regeneration is governed by an intricate network of regulatory cytokines and signalling pathways including FGFs, GDF15, IL-6, PDGF, VEGF, Wnt/β-catenin signalling pathway, Notch signalling pathway and BMPs signalling pathway. Mechanical stimulation can also promote bone regeneration through the transmission of mechanical forces and the activation of cell signalling pathways. Created with BioRender.com. BMP: bone morphogenetic protein; FGFs: fibroblast growth factors; GDF15: growth differentiation factor 15; IL-6: interleukin 6; PDGF: platelet-derived growth factor; VEGF: vascular endothelial growth factor.
Material | Performance parameter | Application form | Product name | Manufacturer | FDA 510(k) number |
---|---|---|---|---|---|
10% porcine type I collagen, 90% bovine bone mineral | Porosity: 70–75%, pore size: 300–1500 μm | Chunk | Bio-Oss Collagen | Geistlich, Wolhusen, Switzerland | K122894 |
Bovine type I collagen, hydroxyapatite | Porosity: 70–88%, pore size: 50–500 μm | Chunks, granules, cylinders | Bongold | Allgens, Beijing, China | K141725 |
Bovine collagen, pork bone minerals | Porosity: 73.42–77.26%, pore size: 0.003–360.86 μm | Cylinders | DSM Biomedical Dental Bone Graft | DSM Biomedical, Exton, PA, USA | K193212 |
Bovine collagen, calcium salts, phosphate | Porosity: 93%, pore size: N/A | Spongy, doughy | CopiOs | Zimmmer, FL, USA | K033679 |
70% bovine I collagen, hydroxyapatite | Porosity: 95%, pore size: 4–200 μm | Stripe | HEALOS | Johnson & Johnson, NJ, USA | K012751 |
Bovine collagen, pork bone minerals | Porosity: N/A, pore size: N/A | Chunks | LegoGraft | Purgo Biologics, Gyeonggi-do, Korea | N/A |
Bovine type I collagen, biphasic bioceramics (15% hydroxyapatite and 85% β-tricalcium phosphate) | Porosity: 89%, pore size: N/A | Stripe, doughy | MASTERGRAFT Strip/Putty | Medtronic, Minneapolis, MN, USA | K082166, K081784 |
Bovine type I collagen, biphasic bioceramics (60% hydroxyapatite and 40% β-tricalcium phosphate) | Porosity: > 90%, pore size: N/A | Stripe | MCS Bone Graft | Bioventus, Durham, NC, USA | K162860 |
8% type I collagen, 92% minerals (30% hydroxyapatite and 70% tricalcium β-phosphate) | Porosity: 70%, pore size: 500–1000 μm | Cylinders | OSTEON III | Dentium, Suwon-si, Korea | K153676 |
45% bovine type I collagen, 55% synthetic calcium phosphate | Porosity: N/A, pore size: N/A | Stripe, chunks, doughy | OssiMend | Collagen Matrix, Paramus, NJ, USA | K052812 |
PMMA bone cement | Porosity: N/A, pore size: N/A | Injectable | Spineplex | Stryker, Portage, MI, USA | K151125, K162062 |
Calcium sulfate, 4% tobramycin sulfate, stearic acid | Porosity: N/A, pore size: N/A | Injectable | Osteoset | Wright Medical Technology, Memphis, TN, USA | K150841 |
Table 1. Bone grafts for clinical research
Material | Performance parameter | Application form | Product name | Manufacturer | FDA 510(k) number |
---|---|---|---|---|---|
10% porcine type I collagen, 90% bovine bone mineral | Porosity: 70–75%, pore size: 300–1500 μm | Chunk | Bio-Oss Collagen | Geistlich, Wolhusen, Switzerland | K122894 |
Bovine type I collagen, hydroxyapatite | Porosity: 70–88%, pore size: 50–500 μm | Chunks, granules, cylinders | Bongold | Allgens, Beijing, China | K141725 |
Bovine collagen, pork bone minerals | Porosity: 73.42–77.26%, pore size: 0.003–360.86 μm | Cylinders | DSM Biomedical Dental Bone Graft | DSM Biomedical, Exton, PA, USA | K193212 |
Bovine collagen, calcium salts, phosphate | Porosity: 93%, pore size: N/A | Spongy, doughy | CopiOs | Zimmmer, FL, USA | K033679 |
70% bovine I collagen, hydroxyapatite | Porosity: 95%, pore size: 4–200 μm | Stripe | HEALOS | Johnson & Johnson, NJ, USA | K012751 |
Bovine collagen, pork bone minerals | Porosity: N/A, pore size: N/A | Chunks | LegoGraft | Purgo Biologics, Gyeonggi-do, Korea | N/A |
Bovine type I collagen, biphasic bioceramics (15% hydroxyapatite and 85% β-tricalcium phosphate) | Porosity: 89%, pore size: N/A | Stripe, doughy | MASTERGRAFT Strip/Putty | Medtronic, Minneapolis, MN, USA | K082166, K081784 |
Bovine type I collagen, biphasic bioceramics (60% hydroxyapatite and 40% β-tricalcium phosphate) | Porosity: > 90%, pore size: N/A | Stripe | MCS Bone Graft | Bioventus, Durham, NC, USA | K162860 |
8% type I collagen, 92% minerals (30% hydroxyapatite and 70% tricalcium β-phosphate) | Porosity: 70%, pore size: 500–1000 μm | Cylinders | OSTEON III | Dentium, Suwon-si, Korea | K153676 |
45% bovine type I collagen, 55% synthetic calcium phosphate | Porosity: N/A, pore size: N/A | Stripe, chunks, doughy | OssiMend | Collagen Matrix, Paramus, NJ, USA | K052812 |
PMMA bone cement | Porosity: N/A, pore size: N/A | Injectable | Spineplex | Stryker, Portage, MI, USA | K151125, K162062 |
Calcium sulfate, 4% tobramycin sulfate, stearic acid | Porosity: N/A, pore size: N/A | Injectable | Osteoset | Wright Medical Technology, Memphis, TN, USA | K150841 |
Figure 3. The performance advantages of polymer microspheres constructed from different materials. Different types of polymer microspheres can be synthesised from natural and synthetic polymers, which mainly have good biocompatibility, high repeatability and controlled degradation behaviour. Created with BioRender.com. PCL: polycaprolactone; PLA: poly(lactic acid); PLGA: poly(lactic-co-glycolic acid).
Figure 4. Different processes for the preparation of microspheres. (A) Single emulsion-solvent extraction. (B) Double emulsion-solvent extraction. The emulsion method is used to prepare microspheres by introducing hydrophilic and hydrophobic monomers into the oil-water interface system to construct the oil-water interface of water in water, and then polymerise on the interface to prepare anisotropic polymer microspheres. (C) Phase separation. The original is to add inorganic salts or non-solvent substances in the mixture of drug and polymer carrier as a coagulant to make the solubility of the polymer suddenly decrease, so that it can be separated from the mixed solution, and wrapped in the surface of the drug to form a protective layer, and then the protective layer solidified by a certain method. (D) Precision particle fabrication. The principle of microfluid-controlled preparation of microspheres is to achieve uniform mixing of materials through microchannel flow, and then form droplets or bubbles in microchannels. Then, by controlling the size and frequency of droplets or bubbles, semi-solid materials gel on the surface of droplets or bubbles, and finally, microspheres with a certain shape and size are generated through solidification and dispersion. Created with Microsoft PowerPoint 2016.
Figure 5. Construction of microsphere scaffolds based on cancellous bone structure and function. Based on the structure and properties of cancellous bone, sintered microspheres, injectable microspheres, and incorporated microspheres can be prepared. The three kinds of scaffolds can be adjusted according to the performance requirements of multiple pore structures, mechanical strength, and adaptive behaviour. Created with BioRender.com.
Type of scaffold | Material | Loaded component | Performance advantage | Reference |
---|---|---|---|---|
Sintered microsphere scaffold | PLA-TMC, chitosan | / | PLA-TMC/chitosan microsphere scaffolds exhibited excellent biocompatibility as they not only managed to improve adhesion and proliferation of MC3T3-E1 cells but fulfilled enhancement of ALP activity as well | |
PTMC, β-TCP | Dexamethasone | The water absorption of the scaffolds can enhance the penetration of nutrients and the excretion of waste, which are beneficial to support the growth of the tissue. Scaffolds delivered dexamethasone in a controlled release manner for sustained release to promote tissue growth | ||
PLGA, nano-hydroxyapatite | DNA | They are highly cytocompatible and can serve as bioactive scaffolds for the release of DNA-loaded calcium phosphate nanoparticles for local gene transfection | ||
PCL | / | Integrated osteochondral scaffolds made of sintered PCL microspheres can provide effective mechanical support and similar compressive strength with native osteochondral tissue. Promotes vascular regeneration and cartilage reconstruction | ||
PLGA, calcium carbonate, hexagonal mesoporous silica | / | Compared with HMS/PLGA scaffolds, the proliferation of MSCs cultured on CC/HMS/PLGA scaffolds was enhanced. When cultured on the CC/HMS/PLGA scaffolds, MSCs also showed significantly enhanced ALP activity and higher calcium secretion compared with HMS/PLGA scaffolds | ||
Biphasic calcium phosphate | / | Biphasic calcium phosphate scaffolds fabricated by indirect SLS printing maintain the physicochemical properties of biphasic calcium phosphate and possess the capacity to recruit host precursor cells to the defect site and promote endogenous bone regeneration possibly via the activation of ERK1/2 signalling. | ||
Injectable microsphere scaffold | GelMA | BMSCs, HUVECs | Development of vascularised bone-like tissue with high levels of OCN and CD31 | |
GelMA, bisphosphonate | Mg2+ | Both in vivo and in vitro experimental results revealed that the magnet-inspired Mg2+-capturing composite microspheres are beneficial to osteogenesis and angiogenesis by stimulating osteoblasts and endothelial cells while restraining osteoclasts, and ultimately effectively promoting cancellous bone regeneration | ||
GelMA | BMSCs | The freeze-dried microspheres of particle size 300 μm and pore size 50 μm rapidly adsorbed murine BMSCs and maintained their viability and osteogenic potential in vitro. In addition, the cell-loaded porous microspheres promoted tissue regeneration when injected locally into a murine bone defect model | ||
MSCs, PDGF-BB | In vitro and in vivo experiments validated that the living GMs exhibit superior secretion properties and anti-inflammatory efficacy and can attenuate osteoarthritis progression by favouring the adherent microenvironment and utilising the synergistic effect of exogenous and endogenous MSCs | |||
PLGA, chitosan | Kartogenin, MSCs | In vivo and in vitro experiments show that PLGA-chitosan microspheres have a high cell-carrying capacity up to 1 × 104 mm?3 and provide effective protection of MSCs to promote their controlled release in the osteoarthritis microenvironment. Simultaneously, kartogenin loaded inside the microspheres effectively cooperated with PLGA-chitosan to induce MSCs to differentiate into chondrocytes | ||
HAMA, PEG | Kartogenin, hydrogenated soya phosphatidylcholine | MHS@PPKHF forms a buffer lubricant layer in the joint space to reduce friction between articular cartilages while releasing encapsulated positively charged PPKHF to the deep cartilage through electromagnetic force, facilitating visualisation of the location of the drug via fluorescence. Moreover, PPKHF facilitates the differentiation of BMSCs into chondrocytes, which are located in the subchondral bone. In animal experiments, the material accelerates cartilage regeneration while allowing monitoring of cartilage layer repair progression via fluorescence signals | ||
HAMA-SA, ChSMA | Chemokines, macrophage antibodies, and engineered cell membrane vesicles | In vitro experiments demonstrated that immune cell-mobilised hydrogel microspheres had excellent macrophage recruitment, capture, and reprogramming abilities. Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5%. Animal experiments also revealed a significant reduction in synovial inflammation and cartilage matrix degradation of osteoarthritis | ||
Thiolated hyaluronic acid | UCMSC-derived exosomes | Extend the retention of exosomes in vivo. The higher enrichment of exosomes on the cartilage surface achieved by chondrocyte-specific targeting peptide significantly improved the therapeutic effects on ageing chondrocytes and promoted the repair of articular cartilage due to their higher efficiency | ||
Incorporated microsphere scaffold | GelMA, nano-hydroxyapatite, chondroitin sulfate A | / | Cell adhesion, proliferation and all-round migration on the scaffold reflected the favourable biocompatibility, as well as proved that the embedded microspheres acted as bridges to facilitate the communication of cells and active factors. The expression of biological factors in vitro and the recovery of animal skull defects in vivo demonstrated that G10-F@Mc scaffolds could induce osteoblastic differentiation of BMSCs and accelerate bone repair | |
GelMA | MSCs | The osteo-callus organoids acting as microniches led to efficient ectopic bone formation and contributed to rapid in situ bone regeneration within 4 weeks in large bone defects. New bone formation under the implantation of osteo-callus organoids exhibited a temporal-forward healing phase which stepped over the chondrogenesis | ||
PLGA, nano-hydroxyapatite | Icariin | The PCL/nano-hydroxyapatite scaffold showed sustained release of icariin as the PCL degraded. The released icariin promoted the osteogenic differentiation of MC3T3-E1 cells. Consistently, in vivo studies showed that the icariin-releasing composite scaffolds promoted calvaria bone healing | ||
Collagen, chitosan, hyaluronic acid, PLGA | Kartogenin | Compared with the surface layer and transitional layer scaffolds group, the results of the dual-layer biomimetic cartilage scaffold group showed that the defects had been filled, the boundary between new cartilage and surrounding tissue was difficult to identify, and the morphology of cells in repair tissue was almost by the normal cartilage after 16 weeks | ||
PLGA, SF, HAp | BMSCs, naringin | The SF/HAp scaffold with naringin microspheres could positively regulate the osteogenic differentiation of BMSCs and promote the differentiation of BMSCs into osteoblasts. Naringin promotes fracture healing through the PI3K/Akt signalling pathway | ||
α-TCP, gelatin, zinc-doped bioglass | / | The long-term release of Zn2+ from zinc-doped bioglass can effectively upregulate the expression of Runx-2, and OCN for promoting osteogenic differentiation of BMSCs. Mg-GMS can regulate the release time and speed of Mg2+, and effectively activate the expression of VEGF, and NGF to promote the reconstruction of the neurovascularisation network. The 3D-printed scaffolds provided mechanical support and interconnecting pore structures |
Table 2. Application of polymer microsphere scaffolds in bone repair
Type of scaffold | Material | Loaded component | Performance advantage | Reference |
---|---|---|---|---|
Sintered microsphere scaffold | PLA-TMC, chitosan | / | PLA-TMC/chitosan microsphere scaffolds exhibited excellent biocompatibility as they not only managed to improve adhesion and proliferation of MC3T3-E1 cells but fulfilled enhancement of ALP activity as well | |
PTMC, β-TCP | Dexamethasone | The water absorption of the scaffolds can enhance the penetration of nutrients and the excretion of waste, which are beneficial to support the growth of the tissue. Scaffolds delivered dexamethasone in a controlled release manner for sustained release to promote tissue growth | ||
PLGA, nano-hydroxyapatite | DNA | They are highly cytocompatible and can serve as bioactive scaffolds for the release of DNA-loaded calcium phosphate nanoparticles for local gene transfection | ||
PCL | / | Integrated osteochondral scaffolds made of sintered PCL microspheres can provide effective mechanical support and similar compressive strength with native osteochondral tissue. Promotes vascular regeneration and cartilage reconstruction | ||
PLGA, calcium carbonate, hexagonal mesoporous silica | / | Compared with HMS/PLGA scaffolds, the proliferation of MSCs cultured on CC/HMS/PLGA scaffolds was enhanced. When cultured on the CC/HMS/PLGA scaffolds, MSCs also showed significantly enhanced ALP activity and higher calcium secretion compared with HMS/PLGA scaffolds | ||
Biphasic calcium phosphate | / | Biphasic calcium phosphate scaffolds fabricated by indirect SLS printing maintain the physicochemical properties of biphasic calcium phosphate and possess the capacity to recruit host precursor cells to the defect site and promote endogenous bone regeneration possibly via the activation of ERK1/2 signalling. | ||
Injectable microsphere scaffold | GelMA | BMSCs, HUVECs | Development of vascularised bone-like tissue with high levels of OCN and CD31 | |
GelMA, bisphosphonate | Mg2+ | Both in vivo and in vitro experimental results revealed that the magnet-inspired Mg2+-capturing composite microspheres are beneficial to osteogenesis and angiogenesis by stimulating osteoblasts and endothelial cells while restraining osteoclasts, and ultimately effectively promoting cancellous bone regeneration | ||
GelMA | BMSCs | The freeze-dried microspheres of particle size 300 μm and pore size 50 μm rapidly adsorbed murine BMSCs and maintained their viability and osteogenic potential in vitro. In addition, the cell-loaded porous microspheres promoted tissue regeneration when injected locally into a murine bone defect model | ||
MSCs, PDGF-BB | In vitro and in vivo experiments validated that the living GMs exhibit superior secretion properties and anti-inflammatory efficacy and can attenuate osteoarthritis progression by favouring the adherent microenvironment and utilising the synergistic effect of exogenous and endogenous MSCs | |||
PLGA, chitosan | Kartogenin, MSCs | In vivo and in vitro experiments show that PLGA-chitosan microspheres have a high cell-carrying capacity up to 1 × 104 mm?3 and provide effective protection of MSCs to promote their controlled release in the osteoarthritis microenvironment. Simultaneously, kartogenin loaded inside the microspheres effectively cooperated with PLGA-chitosan to induce MSCs to differentiate into chondrocytes | ||
HAMA, PEG | Kartogenin, hydrogenated soya phosphatidylcholine | MHS@PPKHF forms a buffer lubricant layer in the joint space to reduce friction between articular cartilages while releasing encapsulated positively charged PPKHF to the deep cartilage through electromagnetic force, facilitating visualisation of the location of the drug via fluorescence. Moreover, PPKHF facilitates the differentiation of BMSCs into chondrocytes, which are located in the subchondral bone. In animal experiments, the material accelerates cartilage regeneration while allowing monitoring of cartilage layer repair progression via fluorescence signals | ||
HAMA-SA, ChSMA | Chemokines, macrophage antibodies, and engineered cell membrane vesicles | In vitro experiments demonstrated that immune cell-mobilised hydrogel microspheres had excellent macrophage recruitment, capture, and reprogramming abilities. Pro-inflammatory macrophages can be transformed into anti-inflammatory macrophages with an efficiency of 88.5%. Animal experiments also revealed a significant reduction in synovial inflammation and cartilage matrix degradation of osteoarthritis | ||
Thiolated hyaluronic acid | UCMSC-derived exosomes | Extend the retention of exosomes in vivo. The higher enrichment of exosomes on the cartilage surface achieved by chondrocyte-specific targeting peptide significantly improved the therapeutic effects on ageing chondrocytes and promoted the repair of articular cartilage due to their higher efficiency | ||
Incorporated microsphere scaffold | GelMA, nano-hydroxyapatite, chondroitin sulfate A | / | Cell adhesion, proliferation and all-round migration on the scaffold reflected the favourable biocompatibility, as well as proved that the embedded microspheres acted as bridges to facilitate the communication of cells and active factors. The expression of biological factors in vitro and the recovery of animal skull defects in vivo demonstrated that G10-F@Mc scaffolds could induce osteoblastic differentiation of BMSCs and accelerate bone repair | |
GelMA | MSCs | The osteo-callus organoids acting as microniches led to efficient ectopic bone formation and contributed to rapid in situ bone regeneration within 4 weeks in large bone defects. New bone formation under the implantation of osteo-callus organoids exhibited a temporal-forward healing phase which stepped over the chondrogenesis | ||
PLGA, nano-hydroxyapatite | Icariin | The PCL/nano-hydroxyapatite scaffold showed sustained release of icariin as the PCL degraded. The released icariin promoted the osteogenic differentiation of MC3T3-E1 cells. Consistently, in vivo studies showed that the icariin-releasing composite scaffolds promoted calvaria bone healing | ||
Collagen, chitosan, hyaluronic acid, PLGA | Kartogenin | Compared with the surface layer and transitional layer scaffolds group, the results of the dual-layer biomimetic cartilage scaffold group showed that the defects had been filled, the boundary between new cartilage and surrounding tissue was difficult to identify, and the morphology of cells in repair tissue was almost by the normal cartilage after 16 weeks | ||
PLGA, SF, HAp | BMSCs, naringin | The SF/HAp scaffold with naringin microspheres could positively regulate the osteogenic differentiation of BMSCs and promote the differentiation of BMSCs into osteoblasts. Naringin promotes fracture healing through the PI3K/Akt signalling pathway | ||
α-TCP, gelatin, zinc-doped bioglass | / | The long-term release of Zn2+ from zinc-doped bioglass can effectively upregulate the expression of Runx-2, and OCN for promoting osteogenic differentiation of BMSCs. Mg-GMS can regulate the release time and speed of Mg2+, and effectively activate the expression of VEGF, and NGF to promote the reconstruction of the neurovascularisation network. The 3D-printed scaffolds provided mechanical support and interconnecting pore structures |
Figure 6. Preparation and application of sintered microspheres (A) Different ways of preparing sintered microsphere scaffolds: thermal sintering, solvent sintering, carbon dioxide sintering and laser sintering. Created with Microsoft PowerPoint 2016. (B) Sintered scaffolds prepared from PLGA porous microspheres. Reprinted from Jose et al.160 (B1) Scanning electron microscopy of PLGA sintered microsphere scaffolds. (B2) Schematic and photographs of sintered PLGA/nHAP pinned and threaded bone grafts. (B3) Staining showing co-culture of PLGA/nHAP scaffolds with BMSCs for Col I and OCN protein expression. (C) CS-PTMC/PLLA/OA-HA/VH sintered microsphere scaffolds. Reprinted from He et al.103 Copyright 2020, Elsevier Inc. (C1) Microsphere SEM. (C2) Finite element analysis of microsphere scaffolds. (D) Characterisation of three integrated scaffolds: non-channel, continuous channel, and discontinuous channel. Reprinted from Gu et al.138 Copyright 2022, Acta Materialia Inc. BMSCs: bone marrow-derived mesenchymal stem cells; Col I: type I collagen; CS-PTMC: chitosan-coated polytrimethylene carbonate; HA/VH: hydroxyapatite/vancomycin hydrochloride; nHAP: nanosized hydroxyapatite; OCN: osteocalcin; PLGA: poly(lactic-co-glycolic acid); SEM: scanning electron microscopy.
Figure 7. Preparation and application of injectable microsphere scaffolds. (A) Schematic diagram of the application of injectable microsphere scaffolds. Created using Microsoft PowerPoint 2016. (B) Promotion of articular cartilage regeneration by PLGA porous microspheres. Reprinted from Bai et al.145 Copyright 2023, Wiley-VCH. (B1) Scanning electron microscopy of PLGA porous microspheres (B2) Stem cell amplification behaviour on the microspheres (C) Sericin-DNA hydrogel microsphere scaffolds for cartilage repair.Reprinted from Shen et al.193 (C1) Synthesis of RGD-SF-DNA microspheres. (C2) Live/dead staining images of BMSCs and differentiation of co-cultured BMSCs into cartilage. (D) Ultrasound contrast imaging of temporalised hydrogel microspheres. Reprinted from Chen et al.196 Copyright 2023, Wiley-VCH. BMSCs: bone marrow mesenchymal stem cell; CEUS: contrast-enhanced ultra sound mode; PFH: perfluorooctane; PLGA: poly(lactic-co-glycolic acid); PLGA@KGN: poly(lactic-co-glycolic acid)@kartogenin; PLGA-CS@KGN: poly(lactic-co-glycolic acid)-chitosan@kartogenin; RGD: Arg-Gly-Asp peptide; RSD-MS: RGD-SF-DNA hydrogel microsphere; SD-MS: SF-DNA hydrogel microsphere; SF-DNA: silk fibroin-DNA; SilMA: silk fibroin methacryloyl; UV: ultraviolet.
Figure 8. Preparation and application of encapsulated microsphere scaffolds (A) Preparation of bioprinting inks by blending microspheres. Created with Microsoft PowerPoint 2016. (B) Composite scaffolds imitate a “lotus” structure by incorporating microspheres with printed scaffolds. Reprinted from Han et al.208 (B1) Bionic schematic of composite scaffolds: Liposome loaded GelMA microspheres and β-TCP scaffolds lighted images as well as electron microscopy images. (B2) β-TCP and GML microspheres Co-culture fluorescence staining images. (B3) Bioink containing microspheres synergising chondrocytes for 3D printing of multiscale composite scaffolds for cartilage repair. Reprinted from Yin et al.210 GelMA: methacrylate gelatin; GM: GelMA group; TGL: composite scaffold incorporating GelMA microsphere@Liposome (GML) into β-TCP scaffold; β-TCP: β-tricalcium phosphate.
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