# Application of Alginate Hydrogels for Next-Generation Articular Cartilage Regeneration

**Authors:** Wei Liu, Henning Madry, Magali Cucchiarini

PMC · DOI: 10.3390/ijms23031147 · International Journal of Molecular Sciences · 2022-01-20

## TL;DR

This review explores how alginate hydrogels can be used to improve cartilage regeneration, especially when combined with cell and gene therapies.

## Contribution

The paper offers a comprehensive evaluation of alginate-based systems for cartilage healing, highlighting their potential in future clinical applications.

## Key findings

- Alginate hydrogels support cartilage healing by delivering cells and therapeutic agents.
- Combining alginate with gene therapy enhances cartilage regeneration outcomes.
- Further research is needed to optimize alginate-based systems for clinical use.

## Abstract

The articular cartilage has insufficient intrinsic healing abilities, and articular cartilage injuries often progress to osteoarthritis. Alginate-based scaffolds are attractive biomaterials for cartilage repair and regeneration, allowing for the delivery of cells and therapeutic drugs and gene sequences. In light of the heterogeneity of findings reporting the benefits of using alginate for cartilage regeneration, a better understanding of alginate-based systems is needed in order to improve the approaches aiming to enhance cartilage regeneration with this compound. This review provides an in-depth evaluation of the literature, focusing on the manipulation of alginate as a tool to support the processes involved in cartilage healing in order to demonstrate how such a material, used as a direct compound or combined with cell and gene therapy and with scaffold-guided gene transfer procedures, may assist cartilage regeneration in an optimal manner for future applications in patients.

## Linked entities

- **Chemicals:** alginate (PubChem CID 5102882)
- **Diseases:** osteoarthritis (MONDO:0005178)

## Full-text entities

- **Genes:** Fgf2 (fibroblast growth factor 2) [NCBI Gene 14173] {aka Fgf-2, Fgf2a, Fgfb, bFGF}, CLU (clusterin) [NCBI Gene 1191] {aka AAG4, APO-J, APOJ, CLI, CLU1, CLU2}, MAPK1 (mitogen-activated protein kinase 1) [NCBI Gene 5594] {aka ERK, ERK-2, ERK2, ERT1, MAPK2, NS13}, Bmp2 (bone morphogenetic protein 2) [NCBI Gene 12156] {aka Bmp2a}, SOX9 (SRY-box transcription factor 9) [NCBI Gene 6662] {aka CMD1, CMPD1, ENH13, SRA1, SRXX2, SRXY10}, LUM (lumican) [NCBI Gene 4060] {aka LDC, SLRR2D}, ELN (elastin) [NCBI Gene 2006] {aka ADCL1, SVAS, WBS, WS}, PTK2 (protein tyrosine kinase 2) [NCBI Gene 5747] {aka FADK, FADK 1, FAK, FAK1, FRNK, PPP1R71}, FGF2 (fibroblast growth factor 2) [NCBI Gene 2247] {aka BFGF, FGF-2, FGFB, HBGF-2}, ASPN (asporin) [NCBI Gene 54829] {aka OS3, PLAP-1, PLAP1, SLRR1C}, IGF1 (insulin like growth factor 1) [NCBI Gene 3479] {aka IGF, IGF-I, IGFI, MGF}, FMOD (fibromodulin) [NCBI Gene 2331] {aka FM, SLRR2E}, CILP (cartilage intermediate layer protein) [NCBI Gene 8483] {aka CILP-1, CILP1, HsT18872}, Tgfb3 (transforming growth factor, beta 3) [NCBI Gene 21809] {aka TGF-beta-3, Tgfb-3}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, TGFBR2 (transforming growth factor beta receptor 2) [NCBI Gene 7048] {aka AAT3, FAA3, LDS1B, LDS2, LDS2B, MFS2}, CD44 (CD44 molecule (IN blood group)) [NCBI Gene 960] {aka CDW44, CSPG8, ECM-III, ECMR-III, H-CAM, HCELL}, TGFB3 (transforming growth factor beta 3) [NCBI Gene 7043] {aka ARVD, ARVD1, LDS5, RNHF, TGF-beta3}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 282089], SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, PRRT2 (proline rich transmembrane protein 2) [NCBI Gene 112476] {aka BFIC2, BFIS2, DSPB3, DYT10, EKD1, FICCA}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, FGFR3 (fibroblast growth factor receptor 3) [NCBI Gene 2261] {aka ACH, CD333, CEK2, HSFGFR3EX, JTK4}, FN1 (fibronectin 1) [NCBI Gene 2335] {aka CIG, ED-B, FINC, FN, FNZ, GFND}, RHO (rhodopsin) [NCBI Gene 6010] {aka CSNBAD1, OPN2, RP4}, MAPK8 (mitogen-activated protein kinase 8) [NCBI Gene 5599] {aka JNK, JNK-46, JNK1, JNK1A2, JNK21B1/2, PRKM8}, BGN (biglycan) [NCBI Gene 633] {aka DSPG1, MRLS, PG-S1, PGI, SEMDX, SLRR1A}, ACAN (aggrecan) [NCBI Gene 176] {aka AGC1, AGCAN, CSPG1, CSPGCP, MSK16, SEDK}, PRG4 (proteoglycan 4) [NCBI Gene 10216] {aka CACP, HAPO, JCAP, MSF, SZP}, BMP7 (bone morphogenetic protein 7) [NCBI Gene 655] {aka OP-1}, DCN (decorin) [NCBI Gene 1634] {aka CSCD, DSPG2, PG40, PGII, PGS2, SLRR1B}, TGM2 (transglutaminase 2) [NCBI Gene 7052] {aka G(h), TG(C), TGC, hTG2, tTG}
- **Diseases:** SCID (MESH:D053632), endotoxin (MESH:D012772), ACI (MESH:D057873), CD (MESH:D003424), Arthrosis (MESH:D010003), hemarthrosis (MESH:D006395), chondral defects restricted (MESH:D002313), Articular cartilage injuries (MESH:D002357), pain (MESH:D010146), hypoxia (MESH:D000860), hypertrophy (MESH:D006984), trochlea CDs (MESH:C566022), femoral condyle (MESH:D000092443), severe combined immunodeficiency (MESH:D016511), necrosis (MESH:D009336), joint destruction (MESH:D008105), cytotoxic (MESH:D064420), hypoxic (MESH:D002534), trochlear groove OCDs (MESH:D000652), chondral defect (MESH:D000013), trauma (MESH:D014947), OCD (MESH:D009771), Microfracture (MESH:D015775), N (MESH:C536108), osteochondral defect (MESH:D010007)
- **Chemicals:** polyvinyl alcohol (MESH:D011142), Co2+ (MESH:D002245), -cellulose (MESH:D002482), CS (MESH:D002586), Na+ (MESH:D012964), graphene oxide (MESH:C000628730), F127 (MESH:C078661), ascorbic acid (MESH:D001205), flavonoid (MESH:D005419), PLA (MESH:C033616), lidocaine (MESH:D008012), rhein (MESH:C020491), AG (MESH:D012834), phosphate (MESH:D010710), CaSO4 (MESH:D002133), polyacrylamide (MESH:C016679), hyaluronate (MESH:D006820), Lysyl-pyridinoline (MESH:C036020), polyethylene glycol terephthalate (MESH:C475920), carbon (MESH:D002244), PVA (MESH:C063253), agarose (MESH:D012685), glycogen (MESH:D006003), N,O-carboxymethyl chitosan (MESH:C077199), Alginate (MESH:D000464), polybutylene terephthalate (MESH:C041733), sulfate (MESH:D013431), polysaccharide (MESH:D011134), Pluronic F127 (MESH:D020442), Ba2+ (MESH:C080430), chitosan (MESH:D048271), calcium (MESH:D002118), keratan sulfate (MESH:D007632), poly(epsilon-caprolactone) (MESH:C016240), PBS (MESH:D007854), MG (MESH:D008274), NaCl (MESH:D012965), poly(lactide-co-glycolide (MESH:D011098), alginic acid (MESH:D000077322), citrate (MESH:D019343), CaCO3 (MESH:D002119), polyelectrolytes (MESH:D000071228), water (MESH:D014867), PGs (MESH:D010715), La3+ (-), catechol (MESH:C034221), calcium phosphate (MESH:C020243), polymethacrylate (MESH:C030613), PMMA (MESH:D019904), CNC (MESH:D000069449), polyphosphate (MESH:D011122), starch (MESH:D013213), PVDF (MESH:C024865), MC (MESH:C061001), lactose (MESH:D007785), poly(glycolic acid) (MESH:D011100), chlorogenic acid (MESH:D002726), poly(2-ethyl-2-oxazoline) (MESH:C511916), periodate (MESH:C009288), sodium citrate (MESH:D000077559)
- **Species:** Ovis aries (domestic sheep, species) [taxon 9940], Oryctolagus cuniculus (domestic rabbit, species) [taxon 9986], Mus musculus (house mouse, species) [taxon 10090], Gallus gallus (bantam, species) [taxon 9031], Pseudomonas (RNA similarity group I, genus) [taxon 286], Escherichia coli (E. coli, species) [taxon 562], Bos taurus (bovine, species) [taxon 9913], Equus caballus (domestic horse, species) [taxon 9796], Phaeophyceae (brown algae, class) [taxon 2870], Azotobacter (genus) [taxon 352], Homo sapiens (human, species) [taxon 9606], Macrocystis pyrifera (giant kelp, species) [taxon 35122], Rattus norvegicus (brown rat, species) [taxon 10116]
- **Cell lines:** N — Homo sapiens (Human), Finite cell line (CVCL_UZ57), Ra — Homo sapiens (Human), Bare lymphocyte syndrome type 2, Transformed cell line (CVCL_B7K7), ) 2 — Homo sapiens (Human), Colon carcinoma, Cancer cell line (CVCL_A628)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC8835677/full.md

## References

402 references — full list in the complete paper: https://tomesphere.com/paper/PMC8835677/full.md

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Source: https://tomesphere.com/paper/PMC8835677