# Subchondral bone repair potential of an osteochondral scaffold augmented with BMP-2 or strontium-enriched amorphous calcium phosphate: a co-culture in vitro model

**Authors:** Manuela Salerno, Marta Columbaro, Stefania Pagani, Janis Locs, Jana Vecstaudza, Laura Dolcini, Milena Fini, Gianluca Giavaresi, Giuseppe Filardo

PMC · DOI: 10.3389/fmed.2026.1738671 · Frontiers in Medicine · 2026-02-11

## TL;DR

Researchers tested two ways to improve bone repair in a lab model, finding that one method better supports bone cell development.

## Contribution

The study introduces and compares two augmentation strategies for an osteochondral scaffold to enhance subchondral bone repair.

## Key findings

- BMP-2-modified scaffolds showed higher metabolic activity and better osteoblast differentiation than controls and Sr-ACP scaffolds.
- Sr-ACP scaffolds tended to stimulate osteoclast activity more than BMP-2 scaffolds.
- Both modified scaffolds improved MSC adhesion and growth compared to the unmodified scaffold.

## Abstract

A collagen/collagen-magnesium-hydroxyapatite (Col/Col-Mg-HA) scaffold is currently used in the clinical practice to address osteochondral lesions (OCL). However, suboptimal bone regeneration still limits its overall reparative potential. The aim of this study was to test in vitro the osteoinductive potential of two different augmentation strategies: the addition of Bone Morphogenetic Protein-2 (BMP-2) or the incorporation of strontium ions-enriched amorphous calcium phosphate (Sr-ACP) granules.

Human mesenchymal stromal cells (MSCs) were seeded on the differently modified scaffolds and unmodified material used as a control, and grown for 14 days in a co-culture system in the presence of primary osteoclasts and conditioned medium of endothelial cells. The potential of the BMP-2- and Sr-ACP-enriched scaffolds compared to the control was then evaluated in terms of MSCs adhesion and morphology, metabolic activity, osteogenic differentiation, and osteoclasts’ markers expression.

Morphologically, both modified scaffolds sustained good cell adhesion. More secreted matrix was observed on the BMP-2 scaffold, together with higher metabolic activity and an upregulation of most of the evaluated osteoblast-related genes compared to the control and the Sr-ACP scaffold. Conversely, in the presence of the Sr-ACP scaffold, lower metabolic activity and a slower activation of osteoblast-related markers, together with a tendency to stimulate the osteoclasts’ activity, was observed.

Overall, both augmentation strategies were able to favor the adhesion and growth of MSCs compared to the unmodified scaffold, with the BMP-2-modified scaffold promoting more the differentiation of MSCs toward a mature osteoblastic phenotype than the Sr-ACP-modified scaffold, and the latter promoting more osteoclast activation.

## Linked entities

- **Chemicals:** hydroxyapatite (PubChem CID 14781), magnesium (PubChem CID 5462224)
- **Species:** Homo sapiens (taxon 9606)

## Full-text entities

- **Genes:** BMP-2 [NCBI Gene 100051701], Bglap (bone gamma carboxyglutamate protein) [NCBI Gene 12096] {aka BGP, Bglap1, OC, OG1, mOC-A}, Alpl (alkaline phosphatase, liver/bone/kidney) [NCBI Gene 11647] {aka ALP, APTNAP, Akp-2, Akp2, TNAP, TNSALP}, CSF1 (colony stimulating factor 1) [NCBI Gene 1435] {aka CSF-1, MCSF, PG-M-CSF}, Runx2 (runt related transcription factor 2) [NCBI Gene 12393] {aka AML3, CBF-alpha-1, Cbf, Cbfa-1, Cbfa1, LS3}, TNFSF11 (TNF superfamily member 11) [NCBI Gene 8600] {aka CD254, ODF, OPGL, OPTB2, RANKL, TNLG6B}, Col1a1 (collagen, type I, alpha 1) [NCBI Gene 12842] {aka Col1a-1, Cola-1, Cola1, Mov-13, Mov13}, GAPDH (glyceraldehyde-3-phosphate dehydrogenase) [NCBI Gene 2597] {aka G3PD, GAPD, HEL-S-162eP}, SENP6 (SUMO specific peptidase 6) [NCBI Gene 26054] {aka SSP1, SUSP1}, BGLAP (bone gamma-carboxyglutamate protein) [NCBI Gene 632] {aka BGP, OC, OCN}, OSCAR (osteoclast associated Ig-like receptor) [NCBI Gene 126014] {aka PIGR3, PIgR-3}, Spp1 (secreted phosphoprotein 1) [NCBI Gene 20750] {aka 2AR, Apl-1, BNSP, BSPI, Bsp, ETA-1}, CTSK (cathepsin K) [NCBI Gene 1513] {aka CTS02, CTSO, CTSO1, CTSO2, PKND, PYCD}, Sparc (secreted acidic cysteine rich glycoprotein) [NCBI Gene 20692] {aka BM-40, ON}, TRAP [NCBI Gene 100187907], SPP1 (secreted phosphoprotein 1) [NCBI Gene 6696] {aka BNSP, BSPI, ETA-1, OPN}, Sp7 (Sp7 transcription factor 7) [NCBI Gene 170574] {aka 6430578P22Rik, C22, Osx}, SP7 (Sp7 transcription factor) [NCBI Gene 121340] {aka OI11, OI12, OSX, osterix}, BMP2 (bone morphogenetic protein 2) [NCBI Gene 650] {aka BDA2, BMP2A, SSFSC, SSFSC1}, ACP5 (acid phosphatase 5, tartrate resistant) [NCBI Gene 54] {aka HPAP, TRACP5a, TRACP5b, TRAP, TRAcP, TrATPase}, CASP3 (caspase 3) [NCBI Gene 836] {aka CPP32, CPP32B, SCA-1}, TNFRSF11B (TNF receptor superfamily member 11b) [NCBI Gene 4982] {aka OCIF, OPG, PDB5, TR1}, Bmp2 (bone morphogenetic protein 2) [NCBI Gene 12156] {aka Bmp2a}, PTH (parathyroid hormone) [NCBI Gene 5741] {aka FIH1, PTH1}, VEGFA (vascular endothelial growth factor A) [NCBI Gene 7422] {aka L-VEGF, MVCD1, VEGF, VPF}, CPAT1 (cerebral palsy, ataxic 1) [NCBI Gene 60502] {aka ACP}, EGF (epidermal growth factor) [NCBI Gene 1950] {aka HOMG4, URG}, RUNX2 (RUNX family transcription factor 2) [NCBI Gene 860] {aka AML3, CBF-alpha-1, CBFA1, CCD, CCD1, CLCD}, ALPP (alkaline phosphatase, placental) [NCBI Gene 250] {aka ALP, PALP, PLAP, PLAP-1}
- **Diseases:** arthritis (MESH:D001168), OC (MESH:D010007), cytotoxic (MESH:D064420), necrosis (MESH:D009336), inflammation (MESH:D007249), trauma (MESH:D014947), osteoclast (MESH:D001862), OA (MESH:D010003)
- **Chemicals:** Dulbecco's modified Eagle medium (-), HA (MESH:D017886), uranyl acetate (MESH:C005460), beta-glycerophosphate (MESH:C031463), dexamethasone (MESH:D003907), Chloroform (MESH:D002725), propylene oxide (MESH:C009068), Alamar Blue (MESH:C005843), CO2 (MESH:D002245), Mg (MESH:D008274), glucose (MESH:D005947), reactive oxygen species (MESH:D017382), calcium (MESH:D002118), Sr (MESH:D013324), glutaraldehyde (MESH:D005976), Heparin (MESH:D006493), osmium tetroxide (MESH:D009993), Hydrocortisone (MESH:D006854), TRIzol (MESH:C411644), cacodylate (MESH:D002101), ethanol (MESH:D000431), EPON 812 (MESH:C004875), calcium phosphate (MESH:C020243), Ascorbic Acid (MESH:D001205), Gentamicin (MESH:D005839)
- **Species:** Homo sapiens (human, species) [taxon 9606], Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** HUVEC — Homo sapiens (Human), Finite cell line (CVCL_2959), OC — Homo sapiens (Human), Induced pluripotent stem cell (CVCL_UD94)

## Full text

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## Figures

6 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12932489/full.md

## References

60 references — full list in the complete paper: https://tomesphere.com/paper/PMC12932489/full.md

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Source: https://tomesphere.com/paper/PMC12932489