Cell-Based Therapies for Post-Traumatic Ankle Osteoarthritis and Osteochondral Lesions of the Talus: A Systematic Scoping Review of an Emerging and Heterogeneous Evidence Base.

Background

Ankle osteoarthritis (OA) differs fundamentally from knee OA: it is predominantly post-traumatic, affects younger and more active patients, and frequently arises from focal osteochondral lesions of the talus (OCLT) rather than diffuse degeneration. Cell-based and orthobiologic therapies-bone marrow aspirate concentrate (BMAC), bone marrow-derived cell transplantation (BMDC), adipose-derived mesenchymal stromal cells (ADMSCs), stromal vascular fraction (SVF), micro-fragmented adipose tissue (mFAT), and peripheral blood-derived products-have been proposed as joint-preserving options, but the evidence base has not been mapped in a way that separates degenerative post-traumatic ankle OA from focal chondral repair, or that distinguishes cells given as a standalone injection from cells given alongside a therapeutic operation.

Methods

We conducted a systematic scoping review following the PRISMA-ScR framework. Human clinical studies applying cell-based therapies to post-traumatic ankle OA and/or OCLT were charted by population, cell source and preparation, mode of delivery, concomitant procedures, follow-up, and reported clinical and structural outcomes. Mode of delivery-standalone intra-articular injection versus adjunct to a concomitant surgical procedure-was pre-specified as a primary analytic axis, because it determines whether an observed effect can be attributed to the cell product at all. Given anticipated clinical and product heterogeneity and the near-absence of controlled trials of standalone injection, no meta-analysis was undertaken; the objective was to map the evidence, characterise its structure, and identify gaps.

Results

Eleven clinical studies were charted. The dominant structural feature of this literature is that in nine of 11 studies the cells were co-administered with a therapeutic surgical procedure-marrow stimulation, autologous osteochondral transplantation, supramalleolar or calcaneal osteotomy, or joint debridement-so that in no charted study can the contribution of the cells be separated from that of the operation. This attribution problem, rather than any efficacy estimate, is the principal finding of the review. The remaining evidence is small, heterogeneous, and uniformly non-randomised (Level of Evidence III-V). Only two studies used standalone injection, and for degenerative post-traumatic ankle OA specifically, the standalone-injection evidence consists of a single case report. Reported clinical outcomes (AOFAS, VAS, FAOS/KOOS, Tegner) and structural surrogates (MOCART, T2-mapping, second-look arthroscopy) were generally favourable, and adverse events were mild and self-limiting; however, no study demonstrated histologically confirmed hyaline regeneration, and no adequately powered randomised trial of standalone injection for degenerative post-traumatic ankle OA was identified.

Conclusions

Cell-based therapies for post-traumatic ankle OA and OCLT show promising but preliminary, hypothesis-generating signals within a fragmented evidence base in which the cellular contribution is confounded by concomitant surgery in nine of 11 charted studies; on present evidence, the field cannot claim an independent effect for the cell product. The knee OA evidence cannot be extrapolated to the ankle because of the joint's distinct biology, aetiology, and lesion pattern. Adequately powered randomised trials of standalone intra-articular injection in well-defined degenerative post-traumatic ankle OA, using standardised product characterisation and a core outcome set with quantitative structural endpoints, are the principal advance needed.