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image of Evaluation of a Kenaf Nanocrystalline Cellulose-based Hydrogel Containing Platelet Lysate for Full-thickness Wound Healing

Abstract

Introduction

Healing full-thickness wounds is often challenging and time-consuming, with complications such as scarring and infections. The standard treatment, split skin grafting, has limitations due to the availability of healthy donors and suitability for immunocompromised patients.

Method

Autologous platelet lysate (PL) has been popular for tissue regenerative potential because it contains growth factors (GF) and is a safer option for bedridden patients with weak immune systems. However, PL has inconsistent clinical efficacy, high costs, and a short half-life. To address these issues, this study explores a novel delivery system by fabricating a chitosan/nanocrystalline cellulose (CS/NCC) hydrogel to sustainably deliver autologous PL to the wound site. Notably, NCC was prepared from kenaf bast fibers using acid hydrolysis and integrated into the CS matrix through physical entrapment without any chemical crosslinkers. The composite hydrogel was then enriched with autologous PL and further characterized for its physicochemical properties, GF release, and compatibility with skin cells. At the molecular level, gene expression of wound healing genes was facilitated using qPCR, revealing that the PL-supplemented hydrogel upregulated the expression of extracellular matrix genes. An study using a full-thickness wound model demonstrated that the CS-NCC-PL hydrogel dressing achieved 81.8% wound closure within 14 days, compared to the control groups.

Result

Histological analysis indicated enhanced re-epithelialization, angiogenesis, and collagen deposition. Particularly, the CS-NCC-PL hydrogel group showed a significantly higher hydroxyproline content (60.62 ± 11.46 μg/100 mg) by day 14. Immunohistochemistry results revealed elevated levels of α-SMA and CD31, markers of myofibroblast presence and angiogenesis, peaking at day 7.

Conclusion

These findings suggest that the CS-NCC-PL hydrogel is a promising personalized wound dressing for bedridden patients, offering improved healing outcomes in hospital settings.

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/content/journals/raddf/10.2174/0126673878323868240924154455
2024-10-11
2024-11-22
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References

  1. Chiara Barsotti M. Losi P. Briganti E. Effect of platelet lysate on human cells involved in different phases of wound healing. PLoS One 2013 8 12 e84753 10.1371/journal.pone.0084753 24386412
    [Google Scholar]
  2. Huang Q. Wu T. Guo Y. Platelet-rich plasma-loaded bioactive chitosan@sodium alginate@gelatin shell-core fibrous hydrogels with enhanced sustained release of growth factors for diabetic foot ulcer healing. Int. J. Biol. Macromol. 2023 234 123722 10.1016/j.ijbiomac.2023.123722 36801280
    [Google Scholar]
  3. Sen C.K. Human Wounds and Its Burden: An Updated Compendium of Estimates. Adv. Wound Care (New Rochelle) 2019 8 2 39 48 10.1089/wound.2019.0946 30809421
    [Google Scholar]
  4. Britto E.J. Nezwek T.A. Popowicz P. Robins M. Wound dressings. StatPearls. StatPearls Publishing 2024 29261956
    [Google Scholar]
  5. Laurano R. Boffito M. Ciardelli G. Chiono V. Wound dressing products: A translational investigation from the bench to the market. Engineered Regeneration 2022 3 2 182 200 10.1016/j.engreg.2022.04.002
    [Google Scholar]
  6. Liang Y. Liang Y. Zhang H. Guo B. Antibacterial biomaterials for skin wound dressing. Asian J Pharm Sci 2022 17 3 353 384 10.1016/j.ajps.2022.01.001 35782328
    [Google Scholar]
  7. Tiwari R. Pathak K. Local drug delivery strategies towards wound healing. Pharmaceutics 2023 15 2 634 10.3390/pharmaceutics15020634 36839956
    [Google Scholar]
  8. Nandhini J. Karthikeyan E. Rajeshkumar S. Nanomaterials for wound healing: Current status and futuristic frontier. Biomedical Technology 2024 6 26 45 10.1016/j.bmt.2023.10.001
    [Google Scholar]
  9. Gowda B.H.J. Mohanto S. Singh A. Nanoparticle-based therapeutic approaches for wound healing: A review of the state-of-the-art. Mater. Today Chem. 2023 27 101319 10.1016/j.mtchem.2022.101319
    [Google Scholar]
  10. Zgheib C. Hilton S.A. Dewberry L.C. Use of cerium oxide nanoparticles conjugated with microRNA-146a to correct the diabetic wound healing impairment. J. Am. Coll. Surg. 2019 228 1 107 115 10.1016/j.jamcollsurg.2018.09.017 30359833
    [Google Scholar]
  11. Dewberry L.C. Niemiec S.M. Hilton S.A. Cerium oxide nanoparticle conjugation to microRNA-146a mechanism of correction for impaired diabetic wound healing. Nanomedicine (Lond.) 2022 40 102483 10.1016/j.nano.2021.102483 34748956
    [Google Scholar]
  12. Sener G. Hilton S.A. Osmond M.J. Injectable, self-healable zwitterionic cryogels with sustained microRNA - cerium oxide nanoparticle release promote accelerated wound healing. Acta Biomater. 2020 101 262 272 10.1016/j.actbio.2019.11.014 31726250
    [Google Scholar]
  13. Guo G. Li X. Ye X. EGF and curcumin co-encapsulated nanoparticle/hydrogel system as potent skin regeneration agent. Int. J. Nanomedicine 2016 11 3993 4009 10.2147/IJN.S104350 27574428
    [Google Scholar]
  14. He Y. Yang W. Zhang C. ROS/pH dual responsive PRP-loaded multifunctional chitosan hydrogels with controlled release of growth factors for skin wound healing. Int. J. Biol. Macromol. 2024 258 Pt 2 128962 10.1016/j.ijbiomac.2023.128962 38145691
    [Google Scholar]
  15. Min K. Tae G. Cellular infiltration in an injectable sulfated cellulose nanocrystal hydrogel and efficient angiogenesis by VEGF loading. Biomater. Res. 2023 27 1 28 10.1186/s40824‑023‑00373‑y 37038209
    [Google Scholar]
  16. Liu G. Yang Y. Liu Y. Li Y. Jiang M. Li Y. Injectable and thermosensitive hydrogel with platelet-rich plasma for enhanced biotherapy of skin wound healing. Adv. Healthc. Mater. 2024 13 12 e2303930 10.1002/adhm.202303930
    [Google Scholar]
  17. Berry-Kilgour C. Cabral J. Wise L. Advancements in the delivery of growth factors and cytokines for the treatment of cutaneous wound indications. Adv. Wound Care (New Rochelle) 2021 10 11 596 622 10.1089/wound.2020.1183 33086946
    [Google Scholar]
  18. Tan J.L. Lash B. Karami R. Restoration of the healing microenvironment in diabetic wounds with matrix-binding IL-1 receptor antagonist. Commun. Biol. 2021 4 1 422 10.1038/s42003‑021‑01913‑9 33772102
    [Google Scholar]
  19. Aziz T. Ullah A. Ali A. Manufactures of bio‐degradable and bio‐based polymers for bio‐materials in the pharmaceutical field. J. Appl. Polym. Sci. 2022 139 29 e52624 10.1002/app.52624
    [Google Scholar]
  20. Mendes B.B. Gómez-Florit M. Araújo A.C. Intrinsically bioactive cryogels based on platelet lysate nanocomposites for hemostasis applications. Biomacromolecules 2020 21 9 3678 3692 10.1021/acs.biomac.0c00787 32786530
    [Google Scholar]
  21. Garcia-Orue I. Gainza G. Gutierrez F.B. Novel nanofibrous dressings containing rhEGF and Aloe vera for wound healing applications. Int. J. Pharm. 2017 523 2 556 566 10.1016/j.ijpharm.2016.11.006 27825864
    [Google Scholar]
  22. Li Y. Leng Q. Pang X. Therapeutic effects of EGF-modified curcumin/chitosan nano-spray on wound healing. Regen. Biomater. 2021 8 2 rbab009 10.1093/rb/rbab009 33738123
    [Google Scholar]
  23. Certelli A. Valente P. Uccelli A. Robust angiogenesis and arteriogenesis in the skin of diabetic mice by transient delivery of engineered VEGF and PDGF-BB proteins in fibrin hydrogels. Front. Bioeng. Biotechnol. 2021 9 688467 10.3389/fbioe.2021.688467 34277588
    [Google Scholar]
  24. Jin T. Fu Z. Zhou L. GelMA loaded with platelet lysate promotes skin regeneration and angiogenesis in pressure ulcers by activating STAT3. Sci. Rep. 2024 14 1 18345 10.1038/s41598‑024‑67304‑2 39112598
    [Google Scholar]
  25. Bhatnagar P. Law J.X. Ng S.F. Chitosan reinforced with kenaf nanocrystalline cellulose as an effective carrier for the delivery of platelet lysate in the acceleration of wound healing. Polymers (Basel) 2021 13 24 4392 10.3390/polym13244392 34960943
    [Google Scholar]
  26. Dahl A. Sultan M. Jung A. Quantitative PCR based expression analysis on a nanoliter scale using polymer nano-well chips. Biomed. Microdevices 2007 9 3 307 314 10.1007/s10544‑006‑9034‑2 17203381
    [Google Scholar]
  27. Ni X. Shan X. Xu L. Adipose-derived stem cells combined with platelet-rich plasma enhance wound healing in a rat model of full-thickness skin defects. Stem Cell Res. Ther. 2021 12 1 226 10.1186/s13287‑021‑02257‑1 33823915
    [Google Scholar]
  28. Truong A-T.N. Kowal-Vern A. Latenser B.A. Wiley D.E. Walter R.J. Comparison of dermal substitutes in wound healing utilizing a nude mouse model. J. Burns Wounds 2005 4 e4 16921409
    [Google Scholar]
  29. Rezvanian M. Ng S.F. Alavi T. Ahmad W. In-vivo evaluation of Alginate-Pectin hydrogel film loaded with Simvastatin for diabetic wound healing in Streptozotocin-induced diabetic rats. Int. J. Biol. Macromol. 2021 171 308 319 10.1016/j.ijbiomac.2020.12.221 33421467
    [Google Scholar]
  30. Khan N.U. Chengfeng X. Jiang M.Q. α-Lactalbumin based scaffolds for infected wound healing and tissue regeneration. Int. J. Pharm. 2024 663 124578 10.1016/j.ijpharm.2024.124578 39153643
    [Google Scholar]
  31. Pakyari M. Farrokhi A. Maharlooei M.K. Ghahary A. Critical role of transforming growth factor beta in different phases of wound healing. Adv. Wound Care (New Rochelle) 2013 2 5 215 224 10.1089/wound.2012.0406 24527344
    [Google Scholar]
  32. Kandhwal M. Behl T. Singh S. Role of matrix metalloproteinase in wound healing. Am. J. Transl. Res. 2022 14 7 4391 4405 35958464
    [Google Scholar]
  33. Caley M.P. Martins V.L.C. O’Toole E.A. Metalloproteinases and wound healing. Adv. Wound Care (New Rochelle) 2015 4 4 225 234 10.1089/wound.2014.0581 25945285
    [Google Scholar]
  34. Freitas-Rodríguez S. Folgueras A.R. López-Otín C. The role of matrix metalloproteinases in aging: Tissue remodeling and beyond. Biochim. Biophys. Acta Mol. Cell Res. 2017 1864 11 2015 2025 10.1016/j.bbamcr.2017.05.007 28499917
    [Google Scholar]
  35. Penn J.W. Grobbelaar A.O. Rolfe K.J. The role of the TGF-β family in wound healing, burns and scarring: A review. Int. J. Burns Trauma 2012 2 1 18 28 22928164
    [Google Scholar]
  36. Loh E.Y.X. Mohamad N. Fauzi M.B. Ng M.H. Ng S.F. Mohd Amin M.C.I. Development of a bacterial cellulose-based hydrogel cell carrier containing keratinocytes and fibroblasts for full-thickness wound healing. Sci. Rep. 2018 8 1 2875 10.1038/s41598‑018‑21174‑7 29440678
    [Google Scholar]
  37. Li J. Chen J. Kirsner R. Pathophysiology of acute wound healing. Clin. Dermatol. 2007 25 1 9 18 10.1016/j.clindermatol.2006.09.007 17276196
    [Google Scholar]
  38. Arai M Matsuzaki T Ihara S 2013
  39. Xu S. Gu M. Wu K. Li G. Unraveling the role of hydroxyproline in maintaining the thermal stability of the collagen triple helix structure using simulation. J. Phys. Chem. B 2019 123 36 7754 7763 10.1021/acs.jpcb.9b05006 31418574
    [Google Scholar]
  40. Summa M. Russo D. Penna I. A biocompatible sodium alginate/povidone iodine film enhances wound healing. Eur. J. Pharm. Biopharm. 2018 122 17 24 10.1016/j.ejpb.2017.10.004 29017952
    [Google Scholar]
  41. Darby I.A. Laverdet B. Bonté F. Desmoulière A. Fibroblasts and myofibroblasts in wound healing. Clin. Cosmet. Investig. Dermatol. 2014 7 301 311 25395868
    [Google Scholar]
  42. Donovan C. Cogswell D. Sun M. Collagen XII regulates stromal wound closure. Exp. Eye Res. 2023 230 109456 10.1016/j.exer.2023.109456 36967080
    [Google Scholar]
  43. Lertkiatmongkol P. Liao D. Mei H. Hu Y. Newman P.J. Endothelial functions of PECAM-1 (CD31). Curr. Opin. Hematol. 2016 ••• 23
    [Google Scholar]
  44. Wu J. Ye J. Zhu J. Heparin-based coacervate of FGF2 improves dermal regeneration by asserting a synergistic role with cell proliferation and endogenous facilitated VEGF for cutaneous wound healing. Biomacromolecules 2016 17 6 2168 2177 10.1021/acs.biomac.6b00398 27196997
    [Google Scholar]
  45. Motegi S. Leitner W.W. Lu M. Pericyte-derived MFG-E8 regulates pathologic angiogenesis. Arterioscler. Thromb. Vasc. Biol. 2011 31 9 2024 2034 10.1161/ATVBAHA.111.232587 21737783
    [Google Scholar]
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  • Article Type:
    Research Article
Keywords: wound healing ; platelet lysate ; hydrogel ; nanocrystalline cellulose ; Chitosan
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