# Self-Assembled Hydrogels: A Novel Drug Delivery System for Osteoarthritis

**Authors:** Hongjuan Wen, Xintong Gu, Kuo Wen, Weibo Qin, Yiwen Geng, Meilun Wang, Chaoya Yang, Qi Wang, Ning Cui, Da Liu

PMC · DOI: 10.3390/cimb48020211 · Current Issues in Molecular Biology · 2026-02-14

## TL;DR

Self-assembled hydrogels offer a promising new way to deliver drugs for osteoarthritis treatment with minimal invasiveness and controlled release.

## Contribution

The paper introduces self-assembled hydrogels as a novel drug delivery system for osteoarthritis with unique properties like in-situ gelation and responsive release.

## Key findings

- Self-assembled hydrogels form 3D networks under physiological conditions without chemical crosslinking agents.
- They enable sustained drug release and are suitable for exosome-based and microenvironment-responsive delivery.
- Despite challenges in clinical translation, they show potential for precise and minimally invasive OA treatment.

## Abstract

Osteoarthritis (OA) is a prevalent degenerative disease of the musculoskeletal system worldwide. Self-assembled hydrogels, as a novel drug delivery system, have demonstrated significant advantages in the treatment of OA. Through non-covalent interactions such as hydrogen bonding, hydrophobic interactions, electrostatic interactions, and π-π stacking, these hydrogels spontaneously form a three-dimensional network structure under physiological conditions without the need for chemical crosslinking agents, offering excellent biocompatibility, injectability, and controllable degradation properties. This system enables in -situ gelation within the joint, minimally invasive injection, sustained and controlled drug release, and intelligent responsive release. It is suitable for various delivery forms, including single-drug targeted delivery, exosome-based composite synergistic delivery, and microenvironment-responsive precise delivery, effectively inhibiting inflammation and promoting cartilage repair. Despite facing challenges in clinical translation, such as consistency in large-scale production, long-term safety evaluation, and regulatory standards, continued optimization in material design and preparation processes holds promise for self-assembled hydrogels to become a key platform for precise and minimally invasive OA treatment, offering new solutions for joint disease therapy.

## Linked entities

- **Diseases:** Osteoarthritis (MONDO:0005178)

## Full-text entities

- **Genes:** MAPK14 (mitogen-activated protein kinase 14) [NCBI Gene 1432] {aka CSBP, CSBP1, CSBP2, CSPB1, EXIP, Mxi2}, TNFRSF1A (TNF receptor superfamily member 1A) [NCBI Gene 7132] {aka CD120a, FPF, TBP1, TNF-R, TNF-R-I, TNF-R55}, Acan (aggrecan) [NCBI Gene 58968] {aka Agc, Agc1}, PRKAA2 (protein kinase AMP-activated catalytic subunit alpha 2) [NCBI Gene 5563] {aka AMPK, AMPK2, AMPKa2, PRKAA}, ADAMTS5 (ADAM metallopeptidase with thrombospondin type 1 motif 5) [NCBI Gene 11096] {aka ADAM-TS 11, ADAM-TS 5, ADAM-TS5, ADAMTS-11, ADAMTS-5, ADAMTS11}, CTNNB1 (catenin beta 1) [NCBI Gene 1499] {aka CTNNB, EVR7, MRD19, NEDSDV, armadillo}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, Akt1 (AKT serine/threonine kinase 1) [NCBI Gene 24185] {aka Akt}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, SIRT1 (sirtuin 1) [NCBI Gene 23411] {aka SIR2, SIR2L1, SIR2alpha}, ADAMTS4 (ADAM metallopeptidase with thrombospondin type 1 motif 4) [NCBI Gene 9507] {aka ADAMTS-2, ADAMTS-4, ADMP-1}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, LTBR (lymphotoxin beta receptor) [NCBI Gene 4055] {aka D12S370, LT-BETA-R, TNF-R-III, TNFCR, TNFR-RP, TNFR2-RP}, PPARGC1A (PPARG coactivator 1 alpha) [NCBI Gene 10891] {aka LEM6, PGC-1(alpha), PGC-1alpha, PGC-1v, PGC1, PGC1A}, Tgfb1 (transforming growth factor, beta 1) [NCBI Gene 59086] {aka Tgfb}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MMP13 (matrix metallopeptidase 13) [NCBI Gene 4322] {aka CLG3, MANDP1, MDST, MMP-13}, IL1B (interleukin 1 beta) [NCBI Gene 3553] {aka IL-1, IL1-BETA, IL1F2, IL1beta}, ULK1 (unc-51 like autophagy activating kinase 1) [NCBI Gene 8408] {aka ATG1, ATG1A, UNC51, Unc51.1, hATG1}, Il1b (interleukin 1 beta) [NCBI Gene 24494] {aka IL-1F2}, Pik3cb (phosphatidylinositol-4,5-bisphosphate 3-kinase, catalytic subunit beta) [NCBI Gene 85243], Tnf (tumor necrosis factor) [NCBI Gene 24835] {aka RATTNF, TNF-alpha, Tnfa}, TNF (tumor necrosis factor) [NCBI Gene 7124] {aka DIF, IMD127, TNF-alpha, TNFA, TNFSF2, TNLG1F}
- **Diseases:** joint injury (MESH:D000092464), cytotoxicity (MESH:D064420), knee OA (MESH:D020370), articular cartilage degradation (MESH:D002357), OA (MESH:D010003), functional disability (MESH:D003291), ischemic (MESH:D002545), pain (MESH:D010146), mitochondrial dysfunction (MESH:D028361), chronic inflammation (MESH:D007249), disease (MESH:D004194), degenerative disease (MESH:D019636), injury to (MESH:D014947)
- **Chemicals:** triamcinolone acetonide (MESH:D014222), glucosamine (MESH:D005944), calcium (MESH:D002118), ROS (MESH:D017382), dopamine (MESH:D004298), glutaraldehyde (MESH:D005976), hydrogen (MESH:D006859), polylactic acid (MESH:C033616), Hydroxyapatite (MESH:D017886), polycaprolactone (MESH:C016240), N-acetylglucosamine (MESH:D000117), dexamethasone (MESH:D003907), amino acids (MESH:D000596), RGD (MESH:C047981), glucuronic acid (MESH:D020723), benzoboroxole (-), genipin (MESH:C007834), Hyaluronic acid (MESH:D006820), carboxymethyl chitosan (MESH:C514968), peptides (MESH:D010455), polyacrylic acid (MESH:C006903), water (MESH:D014867), tyrosine (MESH:D014443), diclofenac sodium (MESH:D004008), polyhistidine (MESH:C033223), polymer (MESH:D011108), polyethylene glycol (MESH:D011092), chitosan (MESH:D048271), phosphorus (MESH:D010758), thioether (MESH:D013440), alginate (MESH:D000464), chondroitin sulfate (MESH:D002809)
- **Species:** Homo sapiens (human, species) [taxon 9606], Rattus norvegicus (brown rat, species) [taxon 10116]

## Full text

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## References

153 references — full list in the complete paper: https://tomesphere.com/paper/PMC12939073/full.md

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Source: https://tomesphere.com/paper/PMC12939073