In this series of patients with chronic fracture-related infection (FRI) and combined bone and soft-tissue defects, managed with such a comprehensive three-stage limb-salvage protocol, we demonstrate a limb-salvage rate of 93.5% (29 out of 31 patients) after a median follow-up of 48 months. Employing our three-stage strategy, including formal soft-tissue reconstruction, we found no infection relapse among the patients with successful limb reconstructions. Functional and patient-satisfaction outcomes were encouraging, showing that our limb-salvage protocol is a valid therapeutic option in such limb-threatening situations and confirming the study’s initial hypothesis.
Two-stage reconstruction for infected post-traumatic injuries has been widely accepted for the past 30 years, with reported success rates of 89–94% [5, 6]. Others have reported favorable results with single-stage protocols [7,8,9]. Mifsud et al.  recently presented 57 cases of chronic osteomyelitis (COM) and infected non-union resolved in a single reconstruction with simultaneous debridement, Ilizarov method and free muscle flap transfer, with high rates of infection eradication (96.5%) and bone union (91.2%). A 5.3% rate of flap failure was observed. Spiegl et al.  presented a prospective series of 25 patients treated with multi-stage protocol with consolidation of 76% and a major complication rate of 0.52 per patient. To the best of our knowledge, there are few studies describing clinical features, treatment protocols and outcomes in such a difficult-to-treat scenario of limb threatening infected (LTI) tibial injuries [9, 19, 20].
The fundamental principle governing any infected-limb-salvage strategy is complete debridement of all necrotic and infected tissues, together with dead-space management, skeletal stabilization, and targeted antimicrobial treatment [5, 6]. Once the initial infection is controlled (iLDC), soft-tissue reconstruction often determines whether a limb can be successfully salvaged. Temporary NPWT between the first and second stage is used to manage such open wounds. It isolates the wound from the hospital environment, preventing recolonization and nosocomial contamination until the following surgery, which should be completed within a maximum of 10 days. Although with acute open fractures the value of NPWT has been debated  for its potential for colonization, during the second stage a new radical debridement, sample-taking and spacer change are performed to avoid new colonization.
The average soft-tissue defect in our cases was 124 cm2, with an overall flap failure rate of 16.7%. Local flap failure rate was 30%, with 9.5% for free flaps. Although not a significant difference, probably reflecting the small sample size, these results reinforce our conviction that a free tissue transfer is the best choice in this scenario. Local flap options are limited, particularly for the middle and distal segments of the tibia, with reports demonstrating better success rates with free flaps . Several studies have demonstrated similar success rates between muscular and fasciocutaneous flaps, in terms of flap survival, complications, and functional recovery in the lower extremity . The main advantage of fasciocutaneous flaps is their ease of subsequent elevation, making them ideal for staged protocols like ours; fasciocutaneous free flaps are therefore preferred, particularly the ALT. Although, free flaps are challenging due to their inherent complexity; microvascular reconstruction can be difficult due to vascular thrombosis, perivascular fibrosis or previous vessel lesion during the initial injury, with the appropriate microsurgical expertise free flaps are much safer . Donor site morbidity and the simultaneous use of external fixator can also present challenges.
Bone reconstruction of infected tibial non-unions with segmental bone defects is a formidable challenge. Despite the encouraging evolution of reconstruction techniques, there is no consensus as to which is the ideal procedure. The current biological techniques for reconstruction of massive bone defects are limited; they can be divided into two main groups: bone-replacement techniques (autologous cancellous bone grafting, induced membrane technique, or free vascularized bone grafting [24,25,26] and bone-regeneration techniques (techniques based on distraction osteogenesis).
Wen et al.  recently published a retrospective study comparing DO, free vascularized fibular transfer, and the Masquelet technique in treatment of 371 post-traumatic long-bone defects, and observed no differences between methods with respect to complication rates, long-term quality of life, chronic pain, or ambulatory status. It should be noted that in the aforementioned study the authors included injuries to the tibia and femur, only 21% of the injuries were infected, and only 10% of the cases required soft-tissue reconstruction—a global scenario very different from ours. In our unit, DO-based techniques are preferred, as they provide unique advantages for infected segmental bone defects of the lower limb. However, the most appropriate bone reconstruction technique is carefully selected for each patient. Generally, bone transport is most suitable for defects > 3.5–4 cm, shortening-lengthening for defects from 1 to 3.5 cm, and acute shortening for defects < 1 cm. Using this protocol resulted in a bone union rate of 100%, with 100% of ASAMI bone scores good/excellent. The benefits of external fixation and DO techniques in the presence of infection are well known, including use of temporary implants far from the infected area, preservation of local vascularity, intraoperative flexibility, and the ability to successfully reconstruct very large bone defects without the restrictions of autograft availability or donor site morbidity. Most importantly, the characteristics of the regenerate bone are most similar to that which was lost .
In this study, the most obvious disadvantage of external fixation was the prolonged course, with an average treatment time of 45 weeks. For bone transport our EFT was 56 weeks, which is comparable to other reports. Wang et al.  reported EFT at 48 weeks in 15 infected tibial non-unions treated with bone transport using a circular frame, while Hohmann et al.  reported EFT of 42 weeks in 32 infected and aseptic tibial non-unions treated with bone transport. In a recent meta-analysis, Aktuglu et al.  evaluated Ilizarov methods for the treatment of infected or non-infected critical-size tibial bone defects, finding a mean EFT of 10.7 months (range 2.5–23.2).
In the authors’ opinion, these are complex techniques that are best performed in experienced bone and joint infection centers which can provide a multidisciplinary team. However, even in specialized centers the number of complications is not trivial, with an average of 1.1 per patient in this cohort, comparable to other studies . Pin-site infection is the most common complication of external fixation [31, 32]; we experienced 32.2% symptomatic pin-site infections, but only three of these required wire/pin replacement. Interestingly, there were 61.1% non-unions at the docking site requiring debridement and autogenous cancellous bone grafting, all resulting in union. The ideal docking-site management protocol is not well established. Ilizarov, classically, proposed a simple compression of the bone ends (closed docking site) with eventual periods of distraction. Some authors, on the other hand, suggest systematically approaching the bone ends (open docking site) with bone grafting as an additional procedure . Based on the results of this study and other previous investigations , currently the docking site is systematically approached for debridement and an iliac crest graft in all cases of bone transport > 4 cm.
Psychological impact and the likelihood of restoration of function are important considerations, as results can be disappointing when expectations are high  and the final outcome is suboptimal. Pain is reported to persist in over 50% of limb salvage patients , but in our series the mean VAS pain rating was 1.0, and 69% of the patients experienced no pain after completing the reconstruction. The ASAMI functional score was good-to-excellent in 86%. Moreover, all poor functional results were related to the incapacity to return to work, considered a reliable measure of treatment outcome . In fact, 83% of our patients who were of working age were able to return to their previous work activities; surprisingly high when compared to some prior reports .
We recognize both the strengths and limitations of the present research. The first limitation lies in the study’s retrospective nature. Retrospective studies rely on chart notes from which important data may be lacking, increasing bias incidence. A second major limitation is our lack of a comparison group; absence of a control group makes it impossible to compare results directly with other limb-salvage protocols in the same scenario. Our third limitation concerns sample size. Our patient cohort was small, although it was comparable in size to other studies with similar patients; this limited the study’s statistical power, and therefore the generalizability of its results. Fourth, the inherent heterogeneity of the study cohort resulted in a broad range of injuries, which rendered them difficult to analyze and compare objectively. Finally, we recognize that all care was provided at a single, high-volume, specialized center; it is difficult to extrapolate these results to less-experienced units. The consistencies of our well-established protocol and strict follow-up add, in our opinion, to the homogeneity and validity of our study. Studies employing prospective data retrieval, larger patient bases and more extensive follow-up are undoubtedly needed.