TABLE 3.

Comparative clinical maturity, evidence, and regulatory status of OA regenerative modalities.

Modality	Clinical stage	Key evidence	Regulatory status	Primary limitation
PRP (Glinkowski et al., 2025)	Established clinical use; numerous completed RCTs	Multiple RCTs vs. HA show pain/function benefit, though heterogeneous results	Device (510(k)) for preparation kits; product itself not FDA-approved as a drug — used off-label	Heterogeneous preparation protocols; inconsistent efficacy across trials
BMAC (Pintore et al., 2023)	Established clinical use; comparative trials vs. PRP/ADSCs completed	Meta-analysis of 27 Level I studies: BMAC/PRP > HA; BMAC not superior to PRP	Autologous, minimally manipulated tissue — generally exempt from FDA drug pathway	Heterogeneous cell yield; no significant advantage over PRP demonstrated
MSCs (Mautner et al., 2023)	Phase 2/3 RCT completed; most advanced cell-based therapy	480-patient RCT: no orthobiologic arm (BMAC, SVF, UC-MSC) superior to corticosteroid injection at 1 year	No FDA-approved MSC product for OA	True hyaline cartilage regeneration not demonstrated; effect largely paracrine
Exosomes (Wang et al., 2025)	Earliest clinical stage; first-in-human pilot trial only	Single ascending-dose pilot trial (n = 41) shows safety, preliminary efficacy signal	No FDA-approved exosome product for any indication; classified as biologic requiring IND	No standardized isolation/manufacturing; large controlled trials lacking
Gene therapy (Brandt et al., 2025)	Most clinically advanced DMOAD candidate; phase 2/3 completed	TissueGene-C (TGF-β1-overexpressing chondrocytes) improved pain/function in phase 2/3 trials	No DMOAD yet approved by FDA; furthest along among DMOAD candidates	Long development timeline; allogeneic cell-gene manufacturing complexity