Orthobiologic Injections Adjunctive to Cartilage-Preserving Surgery May Improve Outcomes for Focal Knee Chondral Defects: A Systematic Review of Randomized Controlled Trials With Subgroup Meta-analyses

To perform a systematic review evaluating the efficacy of orthobiologic injections as adjuncts to cartilage-preserving surgery in improving clinical, radiographic, and histologic outcomes in adults with focal knee cartilage defects. Four databases (PubMed, MEDLINE, EMBASE, and Scopus) were searched through September 2025 for randomized controlled trials assessing adjunctive orthobiologic injections for knee focal chondral lesions. Inclusion criteria were randomized controlled trials reporting pain, function, or cartilage outcomes. Risk of bias was assessed using the Cochrane RoB 2 tool. Five randomized controlled trials involving 217 patients were included. Interventions included platelet-rich plasma (PRP), peripheral blood stem cells, adipose-derived mesenchymal stem cells, and human adipose-derived mesenchymal progenitor cells, administered intra- or postoperatively after cartilage-preserving procedures including subchondral drilling and microfracture. Random-effects subgroup meta-analyses of 2 PRP studies showed a small reduction in pain (mean difference, -0.93; 95% confidence interval, -1.39, -0.47; I = 17%) and improvement in International Knee Documentation Committee scores in the injection group (mean difference, 13.4; 95% confidence interval, 10.1, 16.7; I = 0%). Peripheral blood stem cell + hyaluronic acid significantly improved magnetic resonance imaging and histological cartilage scores versus hyaluronic acid alone. Human adipose-derived mesenchymal progenitor cell + hyaluronic acid improved Western Ontario and McMaster Universities Osteoarthritis Index and histological scores. Adipose-derived mesenchymal stem cells + PRP showed promising arthroscopic and histological outcomes without patient improvement versus PRP alone. Per the RoB 2 tool, 3 studies had some concerns, 1 had low risk, and 1 had high risk of bias. Orthobiologic injections, including peripheral blood stem cells, adipose-derived stem cells, and PRP, appear safe and may provide limited functional, radiographic, and histological benefits in select protocols and populations when used alongside cartilage-preserving surgery for focal knee chondral lesions. Current evidence is insufficient to support such injections as stand-alone procedures. Significant heterogeneity across included studies precludes specific clinical recommendations. Level II, systematic review of Level I and II studies.