Spatiotemporal regulation of endogenous MSCs using a functional injectable hydrogel system for cartilage regeneration
Source abstract
Abstract
Abstract Hydrogels have been extensively favored as drug and cell carriers for the repair of knee cartilage defects. Recruiting mesenchymal stem cells (MSCs) in situ to the defect region could reduce the risk of contamination during cell delivery, which is a highly promising strategy to enhance cartilage repair. Here, a cell-free cartilage tissue engineering (TE) system was developed by applying an injectable chitosan/silk fibroin hydrogel. The hydrogel system could release first stromal cell-derived factor-1 (SDF-1) and then kartogenin (KGN) in a unique sequential drug release mode, which could spatiotemporally promote the recruitment and chondrogenic differentiation of MSCs. This system showed good performance when formulated with SDF-1 (200 ng/mL) and PLGA microspheres loaded with KGN (10 μΜ). The results showed that the hydrogel had good injectability and a reticular porous structure. The microspheres were distributed uniformly in the hydrogel and permitted the sequential release of SDF-1 and KGN. The results of in vitro experiments showed that the hydrogel system had good cytocompatibility and promoted the migration and differentiation of MSCs into chondrocytes. In vivo experiments on articular cartilage defects in rabbits showed that the cell-free hydrogel system was beneficial for cartilage regeneration. Therefore, the composite hydrogel system shows potential for application in cell-free cartilage TE.
Source: crossref · Quality: baseline
Research context
OpenAlex topics: Osteoarthritis Treatment and Mechanisms · Knee injuries and reconstruction techniques · Periodontal Regeneration and Treatments
SciVX discovery tags are terminology-based. OpenAlex topics are source-provided classifications.
References (60)
Show source-provided references
1. Rogan, H., Ilagan, F., Tong, X., Chu, C. R. & Yang, F. Microribbon-hydrogel composite scaffold accelerates cartilage regeneration in vivo with enhanced mechanical properties using mixed stem cells and chondrocytes. Biomaterials 228, 119579 (2020).10.1016/j.biomaterials.2019.119579 ↗
2. Xu, L. et al. Metformin hydrochloride encapsulation by alginate strontium hydrogel for cartilage regeneration by reliving cellular senescence. Biomacromolecules 22, 671–680 (2021).10.1021/acs.biomac.0c01488 ↗
3. Hu, H. et al. miR-23a-3p-abundant small extracellular vesicles released from GelMA/nanoclay hydrogel for cartilage regeneration. J. Extracell. Vesicles 9, 1778883 (2020).10.1080/20013078.2020.1778883 ↗
4. Dong, Y. et al. Regional and sustained dual-release of growth factors from biomimetic tri-layered scaffolds for the repair of large-scale osteochondral defects. Appl. Mater. Today 19, 100548 (2020).10.1016/j.apmt.2019.100548 ↗
5. Zhao, Y. et al. Role of the calcified cartilage layer of an integrated trilayered silk fibroin scaffold used to regenerate osteochondral defects in rabbit knees. ACS Biomater. Sci. Eng. 6, 1208–1216 (2020).10.1021/acsbiomaterials.9b01661 ↗
6. Liu, J. et al. Cell-free scaffolds functionalized with bionic cartilage acellular matrix microspheres to enhance the microfracture treatment of articular cartilage defects. J. Mater. Chem. B 9, 1686–1697 (2021).10.1039/D0TB02616F ↗
7. Howell, M., Liao, Q. & Gee, C. W. Surgical management of osteochondral defects of the knee: an educational review. Curr. Rev. Musculoskelet Med. 14, 60–66 (2021).10.1007/s12178-020-09685-1 ↗
8. Baranowski, M. & Czubak, J. New perspectives in joint cartilage treatment with special emphasis on new types of hydrogels: a review. Ortop. Traumatol. Rehabil. 21, 237–251 (2019).10.5604/01.3001.0013.3716 ↗
9. Kwon, H. et al. Surgical and tissue engineering strategies for articular cartilage and meniscus repair. Nat. Rev. Rheumatol. 15, 550–570 (2019).10.1038/s41584-019-0255-1 ↗
10. Dang, Q. et al. Fabrication and evaluation of thermosensitive chitosan/collagen/α, β-glycerophosphate hydrogels for tissue regeneration. Carbohydr. Polym. 167, 145–157 (2017).10.1016/j.carbpol.2017.03.053 ↗
11. Li, Z., Wang, F., Roy, S., Sen, C. K. & Guan, J. Injectable, highly flexible, and thermosensitive hydrogels capable of delivering superoxide dismutase. Biomacromolecules 10, 3306–3316 (2009).10.1021/bm900900e ↗
12. Bahareh et al. Novel thermosensitive hydrogel composites based on poly(d,l-lactide-co-glycolide) nanoparticles embedded in poly(n-isopropyl acrylamide) with sustained drug-release behavior. J. Appl. Polym. Sci. 131, 40625 (2014).10.1002/app.40625 ↗
13. Byeongmoon et al. Thermosensitive sol–gel reversible hydrogel. Adv. Drug Deliv. Rev. 64, 154–162 (2012).10.1016/j.addr.2012.09.012 ↗
14. Soni, S. S. & Rodell, C. B. Polymeric materials for immune engineering: molecular interaction to biomaterial design. Acta Biomater. 12, 2404 (2021).
15. Nandi, S. K., Kundu, B. & Basu, D. Protein growth factors loaded highly porous chitosan scaffold: a comparison of bone healing properties. Mater. Sci. Eng. C. Mater. Biol. Appl. 33, 1267–1275 (2013).10.1016/j.msec.2012.12.025 ↗
16. LogithKumar, R. et al. A review of chitosan and its derivatives in bone tissue engineering. Carbohydr. Polym. 151, 172–188 (2016).10.1016/j.carbpol.2016.05.049 ↗
17. Costa-Pinto, A. R., Reis, R. L. & Neves, N. M. Scaffolds based bone tissue engineering: the role of chitosan. Tissue Eng. Part. B Rev. 17, 331–347 (2011).10.1089/ten.teb.2010.0704 ↗
18. Huang, H. et al. Directing chondrogenic differentiation of mesenchymal stem cells with a solid-supported chitosan thermogel for cartilage tissue engineering. Biomed. Mater. 9, 035008 (2014).10.1088/1748-6041/9/3/035008 ↗
19. Holland, C., Numata, K., Rnjak-Kovacina, J. & Seib, F. P. The biomedical use of silk: past, present, future. Adv. Healthc. Mater. 8, e1800465 (2019).10.1002/adhm.201800465 ↗
20. Sun, X. et al. In Situ Articular cartilage regeneration through endogenous reparative cell homing using a functional bone marrow-specific scaffolding system. ACS Appl. Mater. Inter. 10, 38715–38728 (2018).10.1021/acsami.8b11687 ↗
21. Lee, C. H. et al. Regeneration of the articular surface of the rabbit synovial joint by cell homing: a proof of concept study. Lancet 376, 440–448 (2010).10.1016/S0140-6736(10)60668-X ↗
22. Zhang, W. et al. An all-silk-derived functional nanosphere matrix for sequential biomolecule delivery and in situ osteochondral regeneration. Bioact. Mater. 5, 832–843 (2020).10.1016/j.bioactmat.2020.05.003 ↗
23. Lee, D. et al. Sequential dual-drug delivery of BMP-2 and alendronate from hydroxyapatite-collagen scaffolds for enhanced bone regeneration. Sci. Rep. 11, 746 (2021).10.1038/s41598-020-80608-3 ↗
24. Chen, P. et al. Radially oriented collagen scaffold with SDF-1 promotes osteochondral repair by facilitating cell homing. Biomaterials 39, 114–123 (2015).10.1016/j.biomaterials.2014.10.049 ↗
25. Theiss, H. D. et al. Dual stem cell therapy after myocardial infarction acts specifically by enhanced homing via the SDF-1/CXCR4 axis. Stem Cell Res. 7, 244–255 (2011).10.1016/j.scr.2011.05.003 ↗
26. Ono, Y., Ishizuka, S., Knudson, C. B. & Knudson, W. Chondroprotective effect of kartogenin on CD44-mediated functions in articular cartilage and chondrocytes. Cartilage 5, 172–180 (2014).10.1177/1947603514528354 ↗
27. Johnson, K. et al. A stem cell-based approach to cartilage repair. Science 336, 717–721 (2012).10.1126/science.1215157 ↗
28. Xu, J. et al. Injectable stem cell-laden supramolecular hydrogels enhance in situ osteochondral regeneration via the sustained co-delivery of hydrophilic and hydrophobic chondrogenic molecules. Biomaterials 210, 51–61 (2019).10.1016/j.biomaterials.2019.04.031 ↗
29. Sinha, V. R. & Trehan, A. Biodegradable microspheres for protein delivery. J. Control. Release 90, 261–280 (2003).10.1016/S0168-3659(03)00194-9 ↗
30. Xu, X. et al. Exosome-mediated delivery of kartogenin for chondrogenesis of synovial fluid-derived mesenchymal stem cells and cartilage regeneration. Biomaterials 269, 120539 (2020).10.1016/j.biomaterials.2020.120539 ↗
31. Hu, Q. et al. Polyethylene glycol modified PAMAM dendrimer delivery of kartogenin to induce chondrogenic differentiation of mesenchymal stem cells. Nanomedicine 13, 2189–2198 (2017).10.1016/j.nano.2017.05.011 ↗
32. Sulaiman, S. B., Idrus, R. B. H. & Hwei, N. M. Gelatin microsphere for cartilage tissue engineering: current and future strategies. Polymers (Basel) 12, 2404 (2020).10.3390/polym12102404 ↗
33. Sun, X., Wang, J., Wang, Y. & Zhang, Q. Collagen-based porous scaffolds containing PLGA microspheres for controlled kartogenin release in cartilage tissue engineering. Artif. Cell. Nanomed. B. 46, 1957–1966 (2018).
34. Matsiko, A., Levingstone, T. J. & O’Brien, F. J. Advanced strategies for articular cartilage defect repair. Materials (Basel) 6, 637–668 (2013).10.3390/ma6020637 ↗
35. Teng, B. et al. A chondrogenesis induction system based on a functionalized hyaluronic acid hydrogel sequentially promoting hMSC proliferation, condensation, differentiation, and matrix deposition. Acta Biomater. 122, 145–159 (2021).10.1016/j.actbio.2020.12.054 ↗
36. Barry, F. & Murphy, M. Mesenchymal stem cells in joint disease and repair. Nat. Rev. Rheumatol. 9, 584–594 (2013).10.1038/nrrheum.2013.109 ↗
37. Sarkaria, S. M., Decker, M. & Ding, L. Bone marrow micro-environment in normal and deranged hematopoiesis: opportunities for regenerative medicine and therapies. Bioessays 40, 10 (2018).10.1002/bies.201700190 ↗
38. Pourrajab, F., Forouzannia, S. K. & Tabatabaee, S. A. Molecular characteristics of bone marrow mesenchymal stem cells, source of regenerative medicine. Int. J. Cardiol. 163, 125–131 (2013).10.1016/j.ijcard.2011.11.017 ↗
39. Huang, H. et al. A functional biphasic biomaterial homing mesenchymal stem cells for in vivo cartilage regeneration. Biomaterials 35, 9608–9619 (2014).10.1016/j.biomaterials.2014.08.020 ↗
40. Steadman, J. R. et al. Outcomes of microfracture for traumatic chondral defects of the knee: average 11-year follow-up. Arthroscopy 19, 477–484 (2003).10.1053/jars.2003.50112 ↗
41. Liu, T. et al. Kartogenin mediates cartilage regeneration by stimulating the IL-6/Stat3-dependent proliferation of cartilage stem/progenitor cells. Biochem. Biophys. Res. Commun. 532, 385–392 (2020).10.1016/j.bbrc.2020.08.059 ↗
42. Shi, W. et al. Structurally and functionally optimized silk-fibroin-gelatin scaffold using 3D printing to repair cartilage injury in vitro and in vivo. Adv. Mater. 29, 1701089 (2017).10.1002/adma.201701089 ↗
43. Reichert, J. C. et al. A tissue engineering solution for segmental defect regeneration in load-bearing long bones. Sci. Transl. Med. 4, 141ra93 (2012).10.1126/scitranslmed.3003720 ↗
44. Gonçalves, R. M., Antunes, J. C. & Barbosa, M. A. Mesenchymal stem cell recruitment by stromal derived factor-1-delivery systems based on chitosan/poly(γ-glutamic acid) polyelectrolyte complexes. Eur. Cell. Mater. 23, 249–260 (2012).10.22203/eCM.v023a19 ↗
45. Chen, Y. et al. Attenuation of subchondral bone abnormal changes in osteoarthritis by inhibition of SDF-1 signaling. Osteoarthr. Cartil. 25, 986–994 (2017).10.1016/j.joca.2017.01.008 ↗
46. Shi, D. et al. Photo-cross-linked scaffold with kartogenin-encapsulated nanoparticles for cartilage regeneration. ACS Nano 10, 1292–1299 (2016).10.1021/acsnano.5b06663 ↗
47. Mi, L., Liu, H., Gao, Y., Miao, H. & Ruan, J. Injectable nanoparticles/hydrogels composite as sustained release system with stromal cell-derived factor-1α for calvarial bone regeneration. Int. J. Biol. Macromol. 101, 341–347 (2017).10.1016/j.ijbiomac.2017.03.098 ↗
48. Zare, P. et al. Alginate sulfate-based hydrogel/nanofiber composite scaffold with controlled Kartogenin delivery for tissue engineering. Carbohydr. Polym. 266, 118123 (2021).10.1016/j.carbpol.2021.118123 ↗
49. Lam, J., Lu, S., Kasper, F. K. & Mikos, A. G. Strategies for controlled delivery of biologics for cartilage repair. Adv. Drug. Deliv. Rev. 84, 123–134 (2015).10.1016/j.addr.2014.06.006 ↗
50. Mottaghitalab, F., Farokhi, M., Shokrgozar, M. A., Atyabi, F. & Hosseinkhani, H. Silk fibroin nanoparticle as a novel drug delivery system. J. Control. Release 206, 161–176 (2015).10.1016/j.jconrel.2015.03.020 ↗
51. Wen, Y. T., Dai, N. T. & Hsu, S. H. Biodegradable water-based polyurethane scaffolds with a sequential release function for cell-free cartilage tissue engineering. Acta Biomater. 88, 301–313 (2019).10.1016/j.actbio.2019.02.044 ↗
52. Sultankulov, B., Berillo, D., Sultankulova, K., Tokay, T. & Saparov, A. Progress in the development of chitosan-based biomaterials for tissue engineering and regenerative medicine. Biomolecules 9, 470 (2019).10.3390/biom9090470 ↗
53. Su, D. et al. Enhancing mechanical properties of silk fibroin hydrogel through restricting the growth of β-sheet domains. ACS Appl. Mater. Inter. 9, 17489–17498 (2017).10.1021/acsami.7b04623 ↗
54. Lu, Q., Zhang, X., Hu, X. & Kaplan, D. L. Green process to prepare silk fibroin/gelatin biomaterial scaffolds. Macromol. Biosci. 10, 289–298 (2010).10.1002/mabi.200900258 ↗
55. Dong, Y. et al. Poly(N-isopropyl-acrylamide)/poly(γ-glutamic acid) thermo-sensitive hydrogels loaded with superoxide dismutase for wound dressing application. Int. J. Nanomed. 15, 1939–1950 (2020).10.2147/IJN.S235609 ↗
56. Ji, W. et al. Incorporation of stromal cell-derived factor-1α in PCL/gelatin electrospun membranes for guided bone regeneration. Biomaterials 34, 735–745 (2013).10.1016/j.biomaterials.2012.10.016 ↗
57. Han, M., Yang, X., Lee, J., Allan, C. H. & Muneoka, K. Development and regeneration of the neonatal digit tip in mice. Dev. Biol. 315, 125–135 (2008).10.1016/j.ydbio.2007.12.025 ↗
58. Zhang, Q. et al. Effects of the fibrous topography-mediated macrophage phenotype transition on the recruitment of mesenchymal stem cells: an in vivo study. Biomaterials 149, 77–87 (2017).10.1016/j.biomaterials.2017.10.007 ↗
59. Zhang, H., Yu, S., Zhao, X., Mao, Z. & Gao, C. Stromal cell-derived factor-1α-encapsulated albumin/heparin nanoparticles for induced stem cell migration and intervertebral disc regeneration in vivo. Acta Biomater. 72, 217–227 (2018).10.1016/j.actbio.2018.03.032 ↗
60. Chen, Y. et al. Sustained release SDF-1α/TGF-β1-loaded silk fibroin-porous gelatin scaffold promotes cartilage repair. ACS Appl. Mater. Inter. 11, 14608–14618 (2019).10.1021/acsami.9b01532 ↗