Cited by 9Osteoarthritis Treatment and MechanismsHydrogels: synthesis, properties, applicationsTissue Engineering and Regenerative Medicine

PEG Reinforced Scaffold Promotes Uniform Distribution of Human MSC-Created Cartilage Matrix

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Riewruja, Kanyakorn, Aguglia, Alyssa M., Hines, Sophie, Makarcyzk, Meagan J., Honsawek, Sittisak, Lin, Hang·2022·Gels

Abstract

Previously, we used a gelatin/hyaluronic acid (GH)-based scaffold to induce chondrogenic differentiation of human bone marrow-derived mesenchymal stromal cells (hBMSC). The results showed that hBMSCs underwent robust chondrogenesis and facilitated in vivo cartilage regeneration. However, it was noticed that the GH scaffolds display a compressive modulus that is markedly lower than native cartilage. In this study, we aimed to enhance the mechanical strength of GH scaffolds without significantly impairing their chondrosupportive property. Specifically, polyethylene glycol diacrylate (PEGDA) and photoinitiators were infiltrated into pre-formed hBMSC-laden GH scaffolds and then photo-crosslinked. Results showed that infiltration of PEG at the beginning of chondrogenesis significantly increased the deposition of glycosaminoglycans (GAGs) in the central area of the scaffold. To explore the mechanism, we compared the cell migration and proliferation in the margin and central areas of GH and PEG-infiltrated GH scaffolds (GH+PEG). Limited cell migration was noticed in both groups, but more proliferating cells were observed in GH than in GH+PEG. Lastly, the in vitro repairing study with bovine cartilage explants showed that PEG- impregnated scaffolds integrated well with host tissues. These results indicate that PEG-GH hybrid scaffolds, created through infiltrating PEG into pre-formed GH scaffolds, display good integration capacity and represent a new tool for the repair of chondral injury.

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  1. [1]Roseti L. Desando G. Cavallo C. Petretta M. Grigolo B. Articular Cartilage Regeneration in Osteoarthritis Cells 2019 8 1305 10.3390/cells8111305 31652798 PMC6912428 · DOI
  2. [2]Ibarra C. Villalobos E. Madrazo-Ibarra A. Velasquillo C. Martinez-Lopez V. Izaguirre A. Olivos-Meza A. Cortes-Gonzalez S. Perez-Jimenez F.J. Vargas-Ramirez A. Arthroscopic Matrix-Assisted Autologous Chondrocyte Transplantation Versus Microfracture: A 6-Year Follow-up of a Prospective Randomized Trial Am. J. Sports Med. 2021 49 2165 2176 10.1177/03635465211010487 34048286 · DOI
  3. [3]Zamborsky R. Danisovic L. Surgical Techniques for Knee Cartilage Repair: An Updated Large-Scale Systematic Review and Network Meta-analysis of Randomized Controlled Trials Arthrosc. J. Arthrosc. Relat. Surg. 2020 36 845 858 10.1016/j.arthro.2019.11.096 32139062 · DOI
  4. [4]Dekker T.J. Aman Z.S. DePhillipo N.N. Dickens J.F. Anz A.W. LaPrade R.F. Chondral Lesions of the Knee: An Evidence-Based Approach J. Bone Jt. Surg. 2021 103 629 645 10.2106/JBJS.20.01161 33470591 · DOI
  5. [5]Urlić I. Ivković A. Cell Sources for Cartilage Repair—Biological and Clinical Perspective Cells 2021 10 2496 10.3390/cells10092496 34572145 PMC8468484 · DOI
  6. [6]Epanomeritakis I.E. Lee E. Lu V. Khan W. The Use of Autologous Chondrocyte and Mesenchymal Stem Cell Implants for the Treatment of Focal Chondral Defects in Human Knee Joints—A Systematic Review and Meta-Analysis Int. J. Mol. Sci. 2022 23 4065 10.3390/ijms23074065 35409424 PMC8999850 · DOI
  7. [7]Wei W. Ma Y. Yao X. Zhou W. Wang X. Li C. Lin J. He Q. Leptihn S. Ouyang H. Advanced hydrogels for the repair of cartilage defects and regeneration Bioact. Mater. 2020 6 998 1011 10.1016/j.bioactmat.2020.09.030 33102942 PMC7557878 · DOI
  8. [8]Lin H. Cheng A.W.-M. Alexander P.G. Beck A.M. Tuan R.S. Cartilage Tissue Engineering Application of Injectable Gelatin Hydrogel with In Situ Visible-Light-Activated Gelation Capability in Both Air and Aqueous Solution Tissue Eng. Part A 2014 20 2402 2411 10.1089/ten.tea.2013.0642 24575844 PMC4161187 · DOI
  9. [9]Lin H. Beck A.M. Shimomura K. Sohn J. Fritch M.R. Deng Y. Kilroy E.J. Tang Y. Alexander P.G. Tuan R.S. Optimization of photocrosslinked gelatin/hyaluronic acid hybrid scaffold for the repair of cartilage defect J. Tissue Eng. Regen. Med. 2019 13 1418 1429 10.1002/term.2883 31066519 PMC6739828 · DOI
  10. [10]Kuang B. Yang Y. Lin H. Infiltration and In-Tissue Polymerization of Photocross-Linked Hydrogel for Effective Fixation of Implants into Cartilage—An In Vitro Study ACS Omega 2019 4 18540 18544 10.1021/acsomega.9b02270 31737812 PMC6854571 · DOI
  11. [11]Tsanaktsidou E. Kammona O. Kiparissides C. Recent Developments in Hyaluronic Acid-Based Hydrogels for Cartilage Tissue Engineering Applications Polymers 2022 14 839 10.3390/polym14040839 35215752 PMC8963043 · DOI
  12. [12]Burke G. Barron V. Geever T. Geever L. Devine D.M. Higginbotham C.L. Evaluation of the materials properties, stability and cell response of a range of PEGDMA hydrogels for tissue engineering applications J. Mech. Behav. Biomed. Mater. 2019 99 1 10 10.1016/j.jmbbm.2019.07.003 31319331 · DOI
  13. [13]Kowalski M.A. Fernandes L.M. Hammond K.E. Labib S. Drissi H. Patel J.M. Cartilage-penetrating hyaluronic acid hydrogel preserves tissue content and reduces chondrocyte catabolism J. Tissue Eng. Regen. Med. 2022 16 1138 1148 10.1002/term.3352 36178309 · DOI
  14. [14]Patel J.M. Loebel C. Saleh K.S. Wise B.C. Bonnevie E.D. Miller L.M. Carey J.L. Burdick J.A. Mauck R.L. Stabilization of Damaged Articular Cartilage with Hydrogel-Mediated Reinforcement and Sealing Adv. Healthc. Mater. 2021 10 e2100315 10.1002/adhm.202100315 33738988 PMC8224478 · DOI
  15. [15]Zhao Y. You Z. Xing D. Li J.J. Zhang Q. Huang H. Li Z. Jiang S. Wu Z. Zhang Y. Comparison of Chondrocytes in Knee Osteoarthritis and Regulation by Scaffold Pore Size and Stiffness Tissue Eng. Part A 2021 27 223 236 10.1089/ten.tea.2020.0085 32539550 · DOI
  16. [16]Wu Y. Zhu L. Jiang H. Liu W. Liu Y. Cao Y. Zhou G. Engineering cartilage substitute with a specific size and shape using porous high-density polyethylene (HDPE) as internal support J. Plast. Reconstr. Aesthetic Surg. 2010 63 e370 e375 10.1016/j.bjps.2009.10.016 19945928 · DOI
  17. [17]Zhao X. Hua Y. Wang T. Ci Z. Zhang Y. Wang X. Lin Q. Zhu L. Zhou G. In vitro Cartilage Regeneration Regulated by a Hydrostatic Pressure Bioreactor Based on Hybrid Photocrosslinkable Hydrogels Front. Bioeng. Biotechnol. 2022 10 916146 10.3389/fbioe.2022.916146 35832408 PMC9273133 · DOI
  18. [18]Farrell M.J. Comeau E.S. Mauck R. Mesenchymal stem cells produce functional cartilage matrix in three-dimensional culture in regions of optimal nutrient supply Eur. Cells Mater. 2012 23 425 440 10.22203/eCM.v023a33 22684531 · DOI
  19. [19]Duan Y. Li X. Zuo X. Shen T. Yu S. Deng L. Gao C. Migration of endothelial cells and mesenchymal stem cells into hyaluronic acid hydrogels with different moduli under induction of pro-inflammatory macrophages J. Mater. Chem. B 2019 7 5478 5489 10.1039/C9TB01126A 31415053 · DOI
  20. [20]Wang C.-Y. Kuo Z.-K. Hsieh M.-K. Ke L.-Y. Chen C.-C. Cheng C.-M. Lai P.-L. Cell migration of preosteoblast cells on a clinical gelatin sponge for 3D bone tissue engineering Biomed. Mater. 2019 15 015005 10.1088/1748-605X/ab4fb5 31634880 · DOI
  21. [21]Schultz K.M. Kyburz K.A. Anseth K.S. Measuring dynamic cell–material interactions and remodeling during 3D human mesenchymal stem cell migration in hydrogels Proc. Natl. Acad. Sci. USA 2015 112 E3757 E3764 10.1073/pnas.1511304112 26150508 PMC4517280 · DOI
  22. [22]Trengove M.A. Di Bella C. O’Connor A.J. The Challenge of Cartilage Integration: Understanding a Major Barrier to Chondral Repair Tissue Eng. Part B Rev. 2022 28 114 128 10.1089/ten.teb.2020.0244 33307976 · DOI
  23. [23]Jelodari S. Sadrabadi A.E. Zarei F. Jahangir S. Azami M. Sheykhhasan M. Hosseini S. New Insights into Cartilage Tissue Engineering: Improvement of Tissue-Scaffold Integration to Enhance Cartilage Regeneration BioMed Res. Int. 2022 2022 7638245 10.1155/2022/7638245 35118158 PMC8807044 · DOI
  24. [24]Athens A.A. Makris E.A. Hu J.C. Induced Collagen Cross-Links Enhance Cartilage Integration PLoS ONE 2013 8 e60719 10.1371/journal.pone.0060719 23593295 PMC3617163 · DOI
  25. [25]Fairbanks B.D. Schwartz M.P. Bowman C.N. Anseth K.S. Photoinitiated polymerization of PEG-diacrylate with lithium phenyl-2,4,6-trimethylbenzoylphosphinate: Polymerization rate and cytocompatibility Biomaterials 2009 30 6702 6707 10.1016/j.biomaterials.2009.08.055 19783300 PMC2896013 · DOI

Cited by

Sorted by citations

Authors
Riewruja, K., Aguglia, A. M., Hines, S., Makarcyzk, M. J., Honsawek, S., & Lin, H.
Affiliations
  • Thai Red Cross Society (TH)
  • University of Pittsburgh (US)
Corresponding author
Lin, Hang
Venue
Gels
Publisher
MDPI AG
Published
2022-12-03
Volume
8
Issue
12
Pages
794
ISSN
2310-2861 (ISSN-L)
OpenAlex
W4311628254
Cited by
9
References
0
Citations by year
2026: 2 · 2025: 3 · 2024: 2 · 2023: 2
FWCI
1.24
Type
journal article
Language
en
Open access
Locations
  • Gels (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
University of Pittsburgh and the Prince Mahidol Award Youth Program
Topics
  • Health Sciences › Medicine › Rheumatology › Osteoarthritis Treatment and Mechanisms
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Medicine › Hydrogels: synthesis, properties, applications
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
poly(ethylene glycol) diacrylate, mesenchymal stem cells, chondrogenic differentiation, cartilage regeneration, scaffold mechanical strength, glycosaminoglycan deposition, cell migration, cell proliferation, photoinitiators, tissue integration

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