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Cited by 31Bone Tissue Engineering MaterialsSpine and Intervertebral Disc PathologyTissue Engineering and Regenerative Medicine

Multi-modulation of immune-inflammatory response using bioactive molecule-integrated PLGA composite for spinal fusion

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Lee, Hye Yeong, Kim, Da-Seul, Hwang, Gwang Yong, Lee, Jun-Kyu, Lee, Hye-Lan, Jung, Ji-Won, Hwang, Sae Yeon, Baek, Seung-Woon +6 more·2023·Materials Today Bio
DOI 10.1016/j.mtbio.2023.100611PMC PMC10034518
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Abstract

Despite current developments in bone substitute technology for spinal fusion, there is a lack of adequate materials for bone regeneration in clinical applications. Recombinant human bone morphogenetic protein-2 (rhBMP-2) is commercially available, but a severe inflammatory response is a known side effect. Bone graft substitutes that enhance osteogenesis without adverse effects are needed. We developed a bioactive molecule-laden PLGA composite with multi-modulation for bone fusion. This bioresorbable composite scaffold was considered for bone tissue engineering. Among the main components, magnesium hydroxide (MH) aids in reduction of acute inflammation affecting disruption of new bone formation. Decellularized bone extracellular matrix (bECM) and demineralized bone matrix (DBM) composites were used for osteoconductive and osteoinductive activities. A bioactive molecule, polydeoxyribonucleotide (PDRN, PN), derived from trout was used for angiogenesis during bone regeneration. A nano-emulsion method that included Span 80 was used to fabricate bioactive PLGA-MH-bECM/DBM-PDRN (PME2/PN) composite to obtain a highly effective and safe scaffold. The synergistic effect provided by PME2/PN improved not only osteogenic and angiogenic gene expression for bone fusion but also improved immunosuppression and polarization of macrophages that were important for bone tissue repair, using a rat model of posterolateral spinal fusion (PLF). It thus had sufficient biocompatibility and bioactivity for spinal fusion.

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  • PDRN inhibits proinflammatory responses in human dermal fibroblasts.

    “Similarly, PDRN inhibits proinflammatory responses in human dermal fibroblasts, further underscoring its immunomodulatory potential [129].”

    From Comparison of Polynucleotide and Polydeoxyribonucleotide in Dermatology: Molecular Mechanisms and Clinical Perspectives (2025) · cites this paper as [129]

    The Results section on inflammatory effects in tissue reports that adding PDRN to the composite reduced M1 macrophage polarization and pro-inflammatory cytokines. That supports an anti-inflammatory effect, but the paper does not establish the claimed effect in human dermal fibroblasts; its in vitro macrophage experiments used murine-derived cells. Page numbers were not available in our copy. (LLM, conf=0.88)

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Cited by

Sorted by citations

Authors
Lee, H. Y., Kim, D.-S., Hwang, G. Y., Lee, J.-K., Lee, H.-L., Jung, J.-W., Hwang, S. Y., Baek, S.-W., Yoon, S. L., Ha, Y., Kim, K. N., Han, I., Han, D. K., & Lee, C. K.
Affiliations
  • Yonsei University (KR)
  • CHA University (KR)
Corresponding author
  • Han, Dong Keun
  • Lee, Chang Kyu
ORCID
Venue
Materials Today Bio
Publisher
Elsevier BV
Published
2023-04
Volume
19
Pages
100611
ISSN
2590-0064 (ISSN-L)
DOI
10.1016/j.mtbio.2023.100611
PMC
PMC10034518
OpenAlex
W4324031268
Cited by
31
References
4
Citations by year
2026: 4 · 2025: 12 · 2024: 11 · 2023: 4
FWCI
2.45
Type
journal article
Language
en
Open access
Licence
Locations
  • Materials Today Bio (publishedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • YUHSpace (Yonsei University Medical Library) (submittedVersion, cc-by-nc-nd)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • CHA University - Pocheon Campus
  • Ministry of Health and Welfare (HI20C0625)
  • Korea Institute for Advancement of Technology
  • Korea Medical Device Development Fund
  • Korea Health Industry Development Institute
  • Ministry of Trade, Industry and Energy (P0015342)
  • National Research Foundation of Korea
  • Yonsei University College of Medicine
  • Ministry of Science, ICT and Future Planning
  • Ministry of Food and Drug Safety (RS-2020-KD000005)
Topics
  • Physical Sciences › Engineering › Biomedical Engineering › Bone Tissue Engineering Materials
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spine and Intervertebral Disc Pathology
  • Health Sciences › Medicine › Surgery › Tissue Engineering and Regenerative Medicine
Keywords
spinal fusion, bone tissue engineering, BMP-2, inflammation modulation, magnesium hydroxide, demineralized bone matrix, polydeoxyribonucleotide, angiogenesis, bone formation, macrophage polarization, immunosuppression, posterolateral fusion, biodegradable scaffolds

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