Novelglue Novelglue

Technology

Mussel adhesion
engineered
for medicine

We re-engineer the molecular mechanics of byssal adhesion into a reproducible recombinant protein — DOPA chemistry, cassette design, and safety evaluation.

Scientific Foundation

Scientific basis of mussel adhesion

Marine mussels (Mytilus galloprovincialis) attach firmly to rocks even under turbulent seas. This adhesion is driven by mussel foot proteins (MFPs) found in the adhesive plaque at the tip of the byssus. Novelglue re-engineers this adhesion system for reproducible, recombinant production.

Mfp-1 — Protective coating (metal surface adhesion)
Mfp-2 — EGF-like domain, protein–protein interaction
Mfp-3 — Primer (~20 mol% DOPA)
Mfp-4 — Elasticity
Mfp-5 — Strongest adhesion (~30 mol% DOPA)
Mfp-6 — Antioxidant activity

DOPA Chemistry

DOPA chemistry

DOPA (3,4-dihydroxyphenylalanine) enables adhesion across wet interfaces via multiple interactions:

Hydrogen bonding

Adheres to hydrophilic surfaces (mica, hydroxyapatite).

Metal coordination

Binds to metal oxide surfaces (Ti, stainless steel).

Hydrophobic interaction

Adheres to nonpolar surfaces (polystyrene).

Covalent bonding

Post-oxidation quinone reacts with amines/thiols via Michael addition.

Surface-force-apparatus measurements report an adhesion energy of W ≈ 3×10⁻⁴ J/m² for Mfp-3 on mica, enough to support ~100 g of force per plaque [*]. A broader mechanistic review is available in Waite 2017 [*].

Cassette Design

Cassette architecture and functional domains

Novelglue designs the FP2 region as a swappable cassette. By fusing functional domains such as EGF, growth factors or targeting peptides, a single platform derives many application-specific adhesives. When an EGF cassette is loaded, EGFR → PI3K/Akt, MEK/ERK signaling supports proliferation and apoptosis suppression; dependence on EGF-containing niche factors in human intestinal organoids is well established in Fujii et al. 2018 [*]. For Novelglue-specific cell adhesion / proliferation data, see Kawakami et al. 2025 [*].

Cell adhesion rate (%)
back buffer 0%
FP121 83%
CellTak™ 89%
noncoated 1%

FP121 reaches CellTak™-level adhesion.

HeLa proliferation (vs. negative)
BSA 0.8×
CellTak™ 2.4×
EGF only 2.5×
FP121 4.7×

FP121 outperforms EGF-only and CellTak™.

Recombinant Expression

Recombinant expression

System Pros Cons Yield
E. coli High yield, low cost, fast No DOPA modification, aggregation 1.0–1.7 g/L
Yeast PTM possible Low yield, long duration Low
Mammalian Full modification Very low yield, high cost Very low

Novelgen combines E. coli expression with mushroom tyrosinase PTM (25°C, 6 h, with ascorbic acid) to achieve both high yield and functional DOPA residues.

Safety Evaluation

Preclinical safety

Novelglue follows a tiered preclinical path: materials characterization → in vitro biological tests → animal studies → GLP/GMP re-execution. The list below tracks our progress against ISO 10993 and OECD guidance. All items will be re-executed under GLP/GMP grade conditions at the PMDA submission stage.

In vitro biological safety

  • ✓
    Cytotoxicity
    ISO 10993-5
  • ✓
    Genotoxicity (Ames / micronucleus)
    ISO 10993-3
  • ✓
    Erythrocyte hemolysis
    ISO 10993-4
  • ✓
    Endotoxin (post LPS-removal)
  • ✓
    Cell migration (scratch assay)
    BALB 3T3, 11.2 µg/mL

Scratch assay with BALB 3T3 cells demonstrated enhanced cell migration at 11.2 µg/mL (Kawakami et al. 2025 [*]).

In vivo (animal studies)

  • ✓
    Systemic toxicity (single / repeat dose)
    OECD GD 129, acute oral LD50 prediction
    GLP-grade data to follow within ~6 months.
  • …
    Sensitization
    ISO 10993-10 (guinea-pig maximization)
  • ✓
    Irritation
    ISO 10993-10 (rabbit intracutaneous)
  • ✓
    Local reaction
    ISO 10993-6 (implantation)
  • …
    Biodegradation
    Residue & tissue reaction after implantation
    If not degraded in 30 days → consider long-term / carcinogenicity studies.
IC50
1.08 ± 0.30 mg/mL
LD50 (estimated)
1.41 ± 0.146 g/kg
Scratch assay
11.2 µg/mL

✓ = completed / … = in progress / — = planned. All items will be re-executed under GLP/GMP grade at PMDA submission. Primary data: Kawakami et al. 2025 (Materials & Design) and related internal studies.

IP Portfolio

IP portfolio

Applications

  • Japan patent application filed
  • PCT international application filed
  • National phase entries planned for US / EU / CN

Strategy

  • Composition of matter (FP121 sequence)
  • Method of use (cell culture / bone / DDS)
  • Manufacturing (DOPA modification conditions)
  • Formulation

引用文献 / References

  1. [1]

    Kawakami, Y. et al. (2025) Development of the FP121 series: Hybrid proteins mimicking marine adhesive proteins with cell adhesion and proliferation activity , Materials & Design , 255 , pp. 114153 .

    View on ScienceDirect →

    Novelglue (FP121 シリーズ) の基盤論文。細胞接着・増殖活性・スクラッチアッセイ等の一次データを含む。

  2. [2]

    Waite, J. H. (2017) Mussel adhesion – essential footwork , Journal of Experimental Biology , 220 , pp. 517-530 .

    DOI: 10.1242/jeb.134056

    イガイ足糸接着の分子メカニズム総説。

  3. [3]

    Lee, H., Dellatore, S. M., Miller, W. M., Messersmith, P. B. (2007) Mussel-inspired surface chemistry for multifunctional coatings , Science , 318 , pp. 426-430 .

    DOI: 10.1126/science.1147241

    DOPA / polydopamine による多機能コーティングの基礎的研究。

  4. [4]

    Lin, Q., Gourdon, D., Sun, C., Holten-Andersen, N., Anderson, T. H., Waite, J. H., Israelachvili, J. N. (2007) Adhesion mechanisms of the mussel foot proteins mfp-1 and mfp-3 , PNAS , 104 , pp. 3782-3786 .

    DOI: 10.1073/pnas.0607852104

    Mfp-3 の mica 表面接着エネルギーを SFA で直接測定した代表論文 (W ≈ 3×10⁻⁴ J/m²)。

  5. [5]

    Hughes, C. S., Postovit, L. M., Lajoie, G. A. (2010) Matrigel: A complex protein mixture required for optimal growth of cell culture , Proteomics , 10 , pp. 1886-1890 .

    DOI: 10.1002/pmic.200900758

    Matrigel の組成の不均一性とロット間変動を定量的に評価。

  6. [6]

    Aisenbrey, E. A., Murphy, W. L. (2020) Synthetic alternatives to Matrigel , Nature Reviews Materials , 5 , pp. 539-551 .

    DOI: 10.1038/s41578-020-0199-8

    Matrigel 代替としての合成・組換え基材の比較レビュー。

  7. [7]

    Fujii, M. et al. (2018) Human intestinal organoids maintain self-renewal capacity and cellular diversity in niche-inspired culture condition , Cell Stem Cell , 23 , pp. 787-793.e6 .

    DOI: 10.1016/j.stem.2018.11.016

    EGF を含むニッチ因子に依存したヒト腸オルガノイド維持条件を示した代表論文。

  8. [8]

    Isozaki, R., Shishio, N., Kudo, K., Mori, M., Ogura, A., Ishikawa, M. (2026) Investigation of the therapeutic effects of marine adhesive protein in a rabbit medial meniscus longitudinal tear model , Japanese Orthopaedic Society for Sports Medicine (JSOA) .

    香川大学医学部 整形外科 × 株式会社ノベルジェン。ウサギ内側半月板縦断裂モデルにおける FP-121 の非臨床試験。

  9. [9]

    Kim, W., Onodera, T., Kondo, E. et al. (2020) Role of synovial-derived cells in meniscal repair , The American Journal of Sports Medicine , 48 , pp. 1406–1415 .

    半月板修復において滑膜由来細胞が果たす役割。FP-121 の生物学的作用仮説の裏付け。

  10. [10]

    Snoeker, B. A. M. et al. (2013) Risk factors for meniscal tears: a systematic review including meta-analysis , Journal of Orthopaedic & Sports Physical Therapy .

    半月板損傷後の長期的な変形性膝関節症リスクが約 4 倍に上昇することを示す。

  11. [11]

    Paradowski, P. T. et al. (2016) Osteoarthritis of the knee after meniscal resection: long-term radiographic outcome , Osteoarthritis and Cartilage .

    半月板切除から 20–30 年後、約 4 人に 3 人が X 線上の大腿脛骨関節 OA を発症。

  12. [12]

    Nepple, J. J. et al. (2012) Meniscal repair outcomes at greater than five years , The Journal of Bone and Joint Surgery (American) .

    5 年以上の追跡における半月板縫合の統合失敗率 23.1%。

  13. [13]

    Schweizer, C. et al. (2022) Meniscal repair failure: timing and risk factors , Knee Surgery, Sports Traumatology, Arthroscopy (KSSTA) .

    半月板縫合後の再断裂の時期分布 (0–2 年 64% / 2–5 年 23% / 5 年超 13%)。

  14. [14]

    Nakagawa, Y. et al. (2015) Macroscopic evaluation of meniscal healing (modified Miguel score) , Osteoarthritis and Cartilage .

    本試験のマクロ評価スコアの出典。

  15. [15]

    Ishida, K. et al. (2007) Histological evaluation of meniscal repair tissue , Tissue Engineering .

    本試験の組織学的評価スコア (modified Ishida score) の原典。

  16. [16]

    Katz, J. N. et al. (2013) Surgery versus physical therapy for a meniscal tear and osteoarthritis , The New England Journal of Medicine .

    米国における半月板部分切除の実施規模および治療選択の議論。