Nonunion after foot and ankle procedures is a challenging and expensive complication, often requiring additional medical care, including revision surgery 1-10. However, augmentation with bone grafting can be used to help facilitate bone healing. There has been significant interest in developing bone graft substitutes for bony fusions 1-10. More recently, there has been growing interest in stem cell products 1-10. Mesenchymal stem cell allografts (MSCAs) are allogenic bone grafts that contain live mesenchymal stem cells 1-10. The purpose of this systematic review is to summarize recent literature regarding the efficacy and safety of MSCA materials in foot and ankle fusion. In November 2025, a query of PubMed and Embase was undertaken to identify all studies evaluating the use of cellular bone allograft materials in foot and ankle fusion procedures. ClinicalTrials.gov was also queried for ongoing clinical trials. The exact search criteria are summarized in the Supporting Information. Studies published between January 1, 2000, and November 15, 2025, were included in the query. Identified studies were screened by two independent reviewers in a double-blinded manner. To be included in the final review, a minimum follow-up of at least 6 months was required. Studies that evaluated the use of MSCA as an independent graft material for any fusion procedures of the ankle, hindfoot, and midfoot were included. Studies that assessed other procedures were included if data pertaining to foot and ankle fusion procedures were reported separately. Studies that assessed other graft materials were included if data pertaining to the use of MSCA were reported separately. Revision or salvage procedures were included in the analysis and were identified as such. The following data were extracted from each study: study title, author names and affiliations, year of publication, type of study design, experimental and control groups, the date range of the procedures performed, age and sex of patients, stem cell formulations, follow-up intervals, comorbid conditions, the type of procedure, fusion scoring, and complications. The main outcome measures were the overall fusion rate and the rate of complications. Outcomes for specific graft materials and fusion procedures were included, if reported. Fusion rates were determined by plain radiographs alone, computed tomography (CT), or a combination of radiographs and CT. Our statistical analysis is summarized within the Supporting Information. The grading of each study is summarized in the Supporting Information. A total of 11 studies met the final inclusion criteria 1-11. The PRISMA flow diagram for all phases of the literature review is provided in the Supporting Information. The level of evidence varied—one study reached Level 1 criteria, two studies reached Level 2, three studies reached Level 3, and five studies reached Level 4 criteria (Table 1). One study was rated of “good quality,” nine studies of “fair quality,” and one study of “poor quality” (Table S1). In total, 684 cases were included in the final cohort, 499 involving an MSCA and 185 involving an autograft. The overall fusion rate was 84.8% (423/499) in the MSCA group and 88.6% (164/185) (p = 0.196). Regarding complications, there was a 10.8% (37/343) and 11.2% (11/98) complication rate in the MSCA and autograft groups, respectively (p = 0.902) (Table 1). MSCA Autograft MSCA + Autograft MSCA: 58 (45–64) years Autograft: 53 (41–63) years Combined: 54 (46–62) years MSCA: 29 males (36%) and 52 females (64%) Autograft: 41 males (47%) and 46 females (53%) Combined: 15 males (48%) and 16 females (52%) Radiographs CT used if obtained during work-up MSCA: 75/81 (92.6%) Autograft: 75/87 (86.2%) MSCA: NR Autograft: NR MSCA Autograft MSCA: 62.4 ± 11.9 years Autograft: 64.0 ± 10.3 years MSCA: 37/44 (84.1%) Autograft: 39/41 (95.1%) MSCA: 5/44 (11.4%) Autograft: 5/41 (12.2%) Men: 52.5 (range: 16–73) years Female: 54 (range: 17–82) years MSCA Autograft MSCA: 56.9 (range: 20.3–79.6) years Autograft: 54.6 (range: 20.7–80.1) years MSCA: 25 males and 27 females Autograft: 26 males and 31 females MSCA: 41/52 (78.8%) Autograft: 50/57 (87.7%) MSCA: 12/52 (23.1%) Autograft: 6/57 (10.5%) MSCA total: 423/499 (84.8%) Autograft total: 164/185 (88.6%) MSCA total: 37/343 (10.8%) Autograft total: 11/98 (11.2%) With regards to fusion rate, the three studies in this systematic review that directly compared MSCA to autograft yielded different conclusions. Frederick et al. found no difference in fusion rate, time-to-fusion, or the rate of revision surgery between MSCA, MSCA with autograft, and autograft groups 1. Anderson et al. reported similar fusion rates and improvement in AOFAS scores between the MSCA and autograft groups, but an overall longer time to radiographic fusion and clinical fusion in the MSCA group 4. In contrast, Myerson et al. reported lower fusion rates in the stem cell group when evaluated with CT imaging 9. However, when measuring fusion based on clinical and radiographic evaluation, there were no differences in fusion rates between the groups. Furthermore, both groups had significant clinical improvement in functional outcome measures. Therefore, MSCA materials may yield a lower fusion potential in subtalar arthrodesis, but the clinical implications of this may not be significant. Complication rates varied widely among the different studies. Excluding nonunion, the rate of complications varied from 0% to 35% in the MSCA cohort 1-10, 11. Two studies directly compared complication rates between MSCA and autograft groups. Anderson et al. reported similar rates of surgical complications between the MSCA and autograft groups, which were all superficial wound dehiscence events that healed with local wound care 4. They reported no complications from autograft harvesting at the proximal tibia. Myerson et al. reported higher procedure-related adverse events in the ACBM group relative to the autograft group (42.3% vs. 24.5%, p = 0.049), but similar graft-related adverse events (15.4% vs. 12.3%, p = 0.639), suggesting that ACBM was not necessarily an inherently less safe graft material 9. The authors reported that only one patient was found to have postoperative donor site pain in the autograft cohort 9. Despite the low rate of donor site morbidity, it is important to consider that MSCA graft use inherently eliminates any donor site complications. Osteogenic materials (e.g., autograft or MSCA) may be particularly useful for patient populations that are at high risk for non-union 2, 7, 8. Dekker et al. specifically investigated the efficacy of MSCA for foot and ankle fusion procedures in a high-risk population, defined as patients who had a smoking history, diabetes, avascular necrosis of the involved bone, active same-site operative infection, history of nonunion, previous same-site surgery, or a gap of 5 mm or greater after joint preparation 2. The authors reported an overall fusion rate of 83%, demonstrating clinical utility of MSCA for cases with a higher risk of nonunion 2. Loveland et al. reported that there were no significant differences (p > 0.05) in fusion rates with MSCA materials at any time point among patients who were diabetic, 65 years of age or older, or obese 8. Rush et al. investigated the utility of MSCA in revision foot and ankle surgery and reported an overall fusion rate of 91.3% without any evidence of graft rejection or complications 7. These studies suggest that the biologic properties of MSCA may provide an effective adjunct for bony healing in cases with a higher risk for nonunion. This study was not without limitations. Many of the studies included in this review were Level 4 evidence, which limits the generalizability and strength of the conclusions therein. Although all studies reported fusion rates for MSCA materials, only three studies compared fusion rates with autograft control groups 2, 7, 8. Furthermore, the overall complication rates varied widely between studies. This makes it difficult to draw conclusions about the overall safety of the different graft materials. In summary, MSC-based allografts present a promising alternative to autograft in certain foot and ankle fusion procedures. These materials may be particularly useful in patients with a higher preoperative risk of nonunion. With regards to differences in other surgical complications and adverse events between MSCA and autograft materials, the literature is conflicting. Further randomized clinical trials are needed to add to this research to further confirm the findings summarized in this systematic review. Mark A. Plantz: conceptualization, methodology, software, data curation, investigation, formal analysis, visualization, writing – original draft, writing – review and editing. Michael P. Foy: manuscript writing, data analysis. Joseph G. Lyons: conceptualization, methodology, data curation, formal analysis, writing – original draft. Sara Shah: manuscript writing/editing, data analysis. Anish R. Kadakia: critical edits, project oversight, conceptualization. The authors have nothing to report. The authors received no specific funding for this work. The authors have nothing to report. The authors declare no conflicts of interest. All data are publicly available, as this is a review of current published literature. Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
Plantz et al. (Sun,) studied this question.