Fixation augmented with micro-fragmented adipose derived stem cells (ORIF+) in simultaneous bilateral femoral shaft fracture: A pilot study

Giuseppe Rovere; Amarildo Smakaj; Giuseppe Rollo; Mario Ronga; Pasquale Quassone; Andrea Perna; Francesco Liuzza; Fernando De Maio; Andrea Fidanza; Michele Coviello; Giuseppe Cottone; Giuseppe Maccagnano; Luigi Meccariello

doi:10.23750/abm.2026.18021

Fixation augmented with micro-fragmented adipose derived stem cells (ORIF+) in simultaneous bilateral femoral shaft fracture: A pilot study

Authors

Giuseppe Rovere Policlinico Tor Vergata Hospital, Rome, Italy; Department of Clinical Science and Translational Medicine, Section of Orthopaedics and Traumatology, University of Rome "Tor Vergata", Rome, Italy
Amarildo Smakaj Department of Orthopaedic Surgery, Bambino Gesù Children's Hospital, IRCCS, Rome, Italy; Department of Biomedicine and Prevention, "Tor Vergata" University of Rome, Rome, Italy
Giuseppe Rollo Department of Orthopedics and Traumatology, Vito Fazzi Hospital, Lecce, Italy
Mario Ronga Orthopaedic and Trauma Operative Unit, Department of Health Sciences, University of Eastern Piedmont, Novara, Italy
Pasquale Quassone Neuroradiology Department, Odpedale del Mare, Asl Napoli 1 centro, Napoli, Italy
Andrea Perna Department of Orthopaedics and Traumatology, Fondazione Casa Sollievo della Sofferenza IRCCS, San Giovanni Rotondo, Italy
Francesco Liuzza Policlinico Tor Vergata Hospital, Rome, Italy; Department of Clinical Science and Translational Medicine, Section of Orthopaedics and Traumatology, University of Rome "Tor Vergata", Rome, Italy
Fernando De Maio Policlinico Tor Vergata Hospital, Rome, Italy; Department of Clinical Science and Translational Medicine, Section of Orthopaedics and Traumatology, University of Rome "Tor Vergata", Rome, Italy
Andrea Fidanza Orthopaedic and Trauma Unit, Dep. Department of Life, Health and Environmental Sciences - University of L'Aquila, L'Aquila, Italy https://orcid.org/0000-0001-7766-0806
Michele Coviello Orthopaedics Unit, Department of Clinical and Experimental Medicine, Faculty of Medicine and Surgery, University of Foggia, Policlinico Riuniti di Foggia, Foggia, Italy
Giuseppe Cottone Orthopaedics Unit, Department of Clinical and Experimental Medicine, Faculty of Medicine and Surgery, University of Foggia, Policlinico Riuniti di Foggia, Foggia, Italy
Giuseppe Maccagnano Orthopaedics Unit, Department of Clinical and Experimental Medicine, Faculty of Medicine and Surgery, University of Foggia, Policlinico Riuniti di Foggia, Foggia, Italy
Luigi Meccariello Department of Orthopedics and Traumatology, AORN San Pio Hospital, Benevento, Italy

Keywords:

Delay Union, Fracture healing, RUS, ORIF augmented: ADSCs

Abstract

Background and aim: Simultaneous bilateral femoral shaft fractures are extremely rare, high-energy injuries often associated with multiple systemic traumas. Intramedullary nailing remains the gold standard for diaphyseal femoral fixation, but alternative strategies may be required in complex or contraindicated cases. This pilot study aimed to assess the feasibility of open reduction and internal fixation biologically augmented with micro-fragmented adipose-derived stem cells (ORIF+) and to evaluate the reliability of the Radiographic Union Score (RUS) as a tool to monitor bone healing in simultaneous bilateral femoral fractures.

Methods: Data from seven patients (14 femurs) with simultaneous bilateral femoral shaft fractures treated between 2016 and 2020 were analyzed. Each patient underwent intramedullary fixation in one limb and ORIF+ in the contralateral limb. Clinical outcomes were assessed using the Visual Analog Scale (VAS) for pain, and radiographic healing was quantified using the RUS on serial radiographs obtained postoperatively and at 1, 3, 6, and 12 months, then annually. The correlation between RUS and VAS was analyzed statistically.

Results: All patients achieved complete bone union without complications. Both RUS and VAS scores showed progressive and significant improvement during follow-up. ORIF+ demonstrated higher RUS values and lower VAS scores at 3 and 6 months, suggesting enhanced early bone healing and pain control. Strong inter-observer agreement was observed for radiographic assessments (κ > 0.85).

Conclusions: Open reduction and plate fixation augmented with micro-fragmented adipose-derived stem cells appears to be a safe and feasible biological alternative for managing complex femoral shaft fractures in selected cases. The Radiographic Union Score proved to be a reliable, reproducible, and objective method for assessing bone healing in this setting. Larger multicentric studies are needed to confirm these preliminary findings.

References

1. Wu CC, Shih CH. Simultaneous bilateral femoral shaft fractures. J Trauma. 1992;32:289-93. doi: 10.1097/00005373-199203000-00004.

2. Stavlas P, Giannoudis PV. Bilateral femoral fractures: does intramedullary nailing increase systemic complications and mortality rates? Injury. 2009;40(11):1125-8. doi: 10.1016/j.injury.2009.09.016.

3. Giannoudis PV, Cohen A, Hinsche A, Stratford T, Matthews SJ, Smith RM. Simultaneous bilateral femoral fractures: systemic complications in 14 cases. Int Orthop. 2000;24:264-7. doi: 10.1007/s002640000161.

4. Rollo G, Ronga M, Bonura EM, et al. Surgical treatment of multifragmentary segmental femur shaft fractures with ORIF and bone graft versus MIPO: a prospective control-group study. Med Glas. 2020;17:498-508. doi: 10.17392/1150-20.

5. Smakaj A, De Mauro D, Rovere G, et al. Clinical application of adipose derived stem cells for the treatment of aseptic non-unions: current stage and future perspectives-systematic review. Int J Mol Sci. 2022;23:3057. doi: 10.3390/ijms23063057.

6. Ulivi M, Meroni V, Viganò M, et al. Micro-fragmented adipose tissue (mFAT) associated with arthroscopic debridement provides functional improvement in knee osteoarthritis: a randomized controlled trial. Knee Surg Sports Traumatol Arthrosc. 2022:1-12. doi: 10.1007/s00167-022-07101-4.

7. Deppe D, Gabriele M, Mazzoleni MG, et al. Interobserver reliability of the modified radiographic union score for tibial and femoral fractures. J Orthop Trauma. 2025;39(10):557-63. doi: 10.1097/BOT.0000000000003032.

8. Perlepe V, Cerato A, Putineanu D, et al. Value of a radiographic score for the assessment of healing of nailed femoral and tibial shaft fractures: a retrospective preliminary study. Eur J Radiol. 2018;98:36-40. doi: 10.1016/j.ejrad.2017.10.020.

9. Garnavos C, Kanakaris NK, Lasanianos NG, Tzortzi P, West RM. New classification system for long-bone fractures supplementing the AO/OTA classification. Orthopedics. 2012 May;35(5):e709-19. doi: 10.3928/01477447-20120426-26.

10. Carsen S, Park SS, Simon DA, Feibel RJ. Treatment with the SIGN nail in closed diaphyseal femur fractures results in acceptable radiographic alignment. Clin Orthop Relat Res. 2015;473(7):2394-401. doi: 10.1007/s11999-015-4290-1.

11. Rollo G, Falzarano G, Ronga M, et al. Challenges in the management of floating knee injuries: results of treatment and outcomes of 224 consecutive cases in 10 years. Injury. 2019;50 Suppl 4:S30-8. doi: 10.1016/j.injury.2019.03.016

12. Saracco M, Fidanza A, Necozione S, Maccauro G, Logroscino G. Could short stems THA be a good bone-saving option even in obese patients? J Clin Med. 2022;11(23):7114. doi: 10.3390/jcm11237114.

13. Chiavaras MM, Bains S, Choudur H, et al. The radiographic union score for hip (RUSH): the use of a checklist to evaluate hip fracture healing improves agreement between radiologists and orthopedic surgeons. Skeletal Radiol. 2013;42(8):1079-88. doi: 10.1007/s00256-013-1605-8.

14. Shih KS, Hsu CC, Hsu TP, Hou SM, Liaw CK. Biomechanical analyses of static and dynamic fixation techniques of retrograde interlocking femoral nailing using nonlinear finite element methods. Comput Methods Programs Biomed. 2014;113:456-64. doi: 10.1016/j.cmpb.2013.11.002.

15. Zhang J, Liu Y, Chen Y, et al. Adipose-derived stem cells: current applications and future directions in the regeneration of multiple tissues. Stem Cells Int. 2020;2020:8810813. doi: 10.1155/2020/8810813.

16. Parrilla C, Saulnier N, Bernardini C, et al. Undifferentiated human adipose tissue-derived stromal cells induce mandibular bone healing in rats. Arch Otolaryngol Head Neck Surg. 2011;137:463-70. doi: 10.1001/archoto.2011.61.

17. Greenwood V, Clausen P, Matuska AM. Micro-fragmented adipose tissue cellular composition varies by processing device and analytical method. Sci Rep. 2022;12:16107. doi: 10.1038/s41598-022-20581-1.

18. Van Genechten W, Vuylsteke K, Martinez PR, Swinnen L, Sas K, Verdonk P. Autologous micro-fragmented adipose tissue (MFAT) to treat symptomatic knee osteoarthritis: early outcomes of a consecutive case series. J Clin Med. 2021;10:2231. doi: 10.3390/jcm10112231

19. Saçak B, Certel F, Akdeniz ZD, et al. Repair of critical size defects using bioactive glass seeded with adipose-derived mesenchymal stem cells. J Biomed Mater Res B Appl Biomater. 2017;105(5):1002-8. doi: 10.1002/jbm.b.33634.

20. Fidanza A, Leonardi E, Migliore E, Calvisi V, Indelli PF. Isolamento, coltura e caratterizzazione di cellule staminali mesenchimali autologhe da donatori di tessuto adiposo e midollo osseo in età avanzata: un approccio alternativo della terapia cellulare in campo ortopedico. Giornale Italiano Di Ortopedia E Traumatologia. 2022;48(2):82-92. doi: 10.32050/0390-0134-392.