1 INTRODUCTION

Chronic osteomyelitis is a recurrent and persistent infection that lasts from months to years and is a common complication of open fractures, internal fixation surgery, diabetic foot, and blood-borne bone infections.1 The common sites of chronic osteomyelitis are mainly tibia and femur.2, 3 Clinical treatment mainly focuses on infection control, filling dead cavity, and repairing local bone and soft tissue defects.4, 5 The main challenges in the treatment of chronic osteomyelitis are the effective filling of long segments of bone and coverage of local soft tissue defects, and the need for permanent bone replacement with implants or prostheses for bone defects resulting from debridement. In recent years, non-degradable materials represented by polymethyl methacrylate6 and a variety of degradable materials, such as calcium sulfate,7 synthetic biodegradable polymers,8 hydrogels, and bio-derived polymers,9 as well as 3D printed models,10 have been developed to provide patients with a variety of options for bone replacement. However, for chronic osteomyelitis with local soft tissue defects, the replacement of implants or prostheses as bone must be temporary, and how to use an effective way to achieve wound repair is a more difficult and clinical problem in trauma orthopaedics. Studies have shown that flap, musculocutaneous flap, and greater omentum transplantation can effectively repair complex wounds and wound surfaces of lower limbs caused by various causes.11, 12 Among them, the flap is the most used clinically repairing lower limb soft tissue defect wound treatment, including the sural nerve nutritional flap,13, 14 sural artery femoral anterolateral flap perforators flap,15 posterior tibial artery perforators flap, iliac groin flap,16, 17 etc., with the development of microscopy techniques, all kinds of skin flap design to get continuous improvement. The key to the treatment of patients with chronic osteomyelitis complicated with soft tissue defect is to select appropriate flaps, fascia flaps, muscle flaps, and bone flaps to fill the local soft tissue defect and cover the wound according to the location, scope, and type of the defect, which provides the possibility of permanent prosthesis implantation for these patients. The purpose of our study was to investigate the effectiveness of different tissue grafting techniques in the treatment of soft tissue defects complicated by chronic osteomyelitis in clinical practice and to provide a reference value for the future treatment of soft tissue defects complicated by chronic osteomyelitis. Through retrospective analysis of 21 cases of adult patients with chronic osteomyelitis complicated with soft tissue defects in our hospital, our study explored the clinical application value and significance of different orthopaedic treatment options in patients with chronic osteomyelitis complicated with local soft tissue defects and found that the tissue transplantation technique was safe and effective to repair the local soft tissue defect in chronic osteomyelitis.

2 METHODS 2.1 General information

This study was approved by the ethics Committee of our hospital, retrospectively analysed patients diagnosed as chronic osteomyelitis with soft tissue defect in our Hospital from October 2016 to January 2021.

Inclusion criteria: (a) age ≥18 years; (b) a clear diagnosis of chronic osteomyelitis with bone defect in four limbs; and (c) incision closure barriers after bone cement or 3D printed prosthesis placement, accompanied by local soft tissue defects of varying degrees.

Exclusion criteria: (a) chronic osteomyelitis in acute inflammatory phase; (b) local soft tissue wounds or defects caused by other reasons, such as skin and soft tissue malignant tumours; (c) bone defect caused by other reasons, such as bone tumour, bone tuberculosis, etc.; (d) accompanied by severe comorbidities such as grade IV heart failure and severe immune dysfunction; and (e) follow-up data were missing.

A total of 21 patients meeting the criteria were included, including 19 males and 2 females.

2.2 Surgical method

All operations were performed by the same senior orthopaedic surgeon. Procedure: After selecting the appropriate anaesthesia method and position according to the scope and site of the wound: (a) After rinsing the wound with normal saline, the throat swab was scraped and scraped to take the wound secretions for bacterial culture and drug sensitivity test. Culture methods include general bacterial and fungal smear identification, general bacterial and fungal culture and drug sensitivity test, anaerobic and aerobic bacteria culture, and drug sensitivity test. (b) A 50 mL syringe with a needle was used to compress the gap between the internal fixator and the tissue, and a large amount of normal saline, 3% hydrogen peroxide and 2.5% iodophor were used to repeatedly rinse and scrape the wound to remove the necrotic or infected tissue. (c) The wound was soaked in 2.5% iodophor solution for 10 to 15 minutes.18 (d) Determine the specific wound closure operation according to the condition of the wound.

2.3 Data collection and statistics

The hospital electronic medical record system was used to collect the general information of patients, including gender, age, body mass index (BMI), length of stay, total cost of stay, surgical methods, postoperative complications, and further treatment plan. SPSS 21 was used to analyse data. Continuous variables were expressed as mean ± SD, and categorical variables were expressed as frequency or percentage.

3 RESULTS 3.1 General information of patients

A total of 21 standard patients were included, including 2 females and 19 males, with an average age of 47.29 ± 18.18 years, an average BMI of 24.77 ± 3.89 kg/m2, and an average non-healing time of 31.05 ± 55.63 months. The average operation time was 316.13 ± 133.87 minutes, the average intraoperative blood loss was 226.87 ± 270.74 mL, the average hospitalisation time was 48.81 ± 20.43 days, and the average hospitalisation cost was 46 528.26 ± 37 183.35 yuan. One patient was complicated with hypertension, three patients were complicated with type II diabetes, and one patient was complicated with coronary heart disease. After admission, the above four patients were regularly treated with medication, which could be controlled, two patients were complicated with depression, and one patient was complicated with lumbar fracture and total paralysis of lower limbs. There were seven patients with positive wound bacterial culture, including two cases of Staphylococcus aureus, one case of Pseudomonas aeruginosa, one case of Staphylococcus hemolysis, one case of Acinetobacter baumannii, one case of Klebobacter aerigenesis, and one case of Enterobacter cloacae. Among the 21 patients, 6 patients received intraoperative blood transfusion, with an average blood transfusion volume of 283.33 ± 56.89 mL Table 1.

TABLE 1. General information of patients Item Mean Age 47.29 ± 18.18 (19-83) Gender (male:female) 19:2 Body mass index (kg/m2) 24.77 ± 3.89 (17.65-31.35) American Society of Anesthesiologists Classification (I:II:III) 7:12:2 Hospital stays (d) 48.81 ± 20.43 (15-93) The operation time (min) 316.13 ± 133.87 (112.00-648.00) Intraoperative blood loss (mL) 226.87 ± 270.74 (20.00-1080.00) Hospitalisation cost (yuan) 46 528.26 ± 37 183.35 (6182.95-145530.10) Intraoperative blood loss (mL) 226.87 ± 270.74 (20.00-1080.00) Preoperative HGB, haemoglobin (g/L) 127.67 ± 20.25 (93-162) Preoperative HCT, haematocrit 0.38 ± 0.05 (0.29-0.45) Preoperative PLT, platelet count (/L) 229.67 ± 70.27 (104-415) Intraoperative blood loss (mL) 226.87 ± 270.74 (20.00-1080.00) Preoperative PT, Prothrombin time (s) 11.16 ± 0.85 (10.10-13.60) Preoperative APTT, activated partial thromboplastin time (s) 34.15 ± 4.19 (26.60 ± 39.80) Preoperative ALT, alanine aminotransferase (U/L) 35.89 ± 54.15 (7.00-255.00) Preoperative AST, aspartate aminotransferase (U/L) 22.83 ± 16.16 (10.00-83.00) Preoperative ALB, albumin (g/L) 38.38 ± 4.31 (30.50-46.30) Preoperative CR, serum creatinine (μmol/L) 68.89 ± 14.33 (43.00-101.00) Note: The above parameters related to surgery and hospitalisation were all for patients undergoing soft tissue coverage surgery.

The pathological results of all 21 patients were dead bone and inflammatory necrotic tissue. Among the 21 patients with chronic osteomyelitis complicated with local soft tissue defect, 1 case was caused by diabetic foot, 20 cases were caused by trauma, including 13 cases of car accident injury, 4 cases of high fall injury, and 3 cases of other types of trauma. All the 20 patients with chronic osteomyelitis caused by injury were chronic osteomyelitis after fracture operation, including 11 cases of open fracture and 9 cases of closed fracture. For open fractures, four patients underwent internal fixation (including intramedullary nails and titanium plates), seven patients underwent external fixation, and all patients underwent internal fixation for closed fractures Supplemental Figure S1.

Among the 20 patients with chronic osteomyelitis caused by trauma, there were 13 patients with chronic osteomyelitis of the tibia combined with local soft tissue defect, of which 1 patient was repaired with soleus muscle flap combined with autologous skin graft, and the other 12 patients were transferred to cover the defect area with reverse sural neurotrophic muscle flap. Twelve cases with retrograde sural nerve nutrition myocutaneous flap transfer in patients with postoperative complications observed in four patients, including two cases of patients with different degree of skin flap necrosis in distal, and bone cement prosthesis was exposed in one case because of skin flap necrosis, debridement again after local rotation skin flap transfer to cover the defect, one case of patients with skin flap necrosis range is small, prosthesis did not expose, partial treatment after improving. Among the remaining two patients with complications, one patient developed sub-flap hematoma after surgery, and the flap survived well after timely removal of the hematoma, and the other patient suffered secondary necrosis in the skin graft area of the wound.

One patient with chronic osteomyelitis of femur complicated with local soft tissue defect was transferred by ilioinguinal skin flap to repair the defect area, and pedicles were broken again in the second stage. Follow-up of 3 and 6 months after the operation found that scar was acceptable and hip joint activity was not disagreeable. A case of chronic osteomyelitis of humerus complicated with local soft tissue defect, local Z flap was used to repair the small defect scope. With slow bone osteomyelitis in four patients complicated with local soft tissue defect, both of them were high falling injury causes, of which one patient plantar medial flap transfer repair, three cases were treated by sural nerve nutrition myocutaneous flap to repair the defect, 3 and 6 months follow-up flap and postoperative secondary wound skin graft healed well, and scarring is acceptable. One patient with chronic osteomyelitis of the first metatarsal bone caused by diabetic foot was covered with medial plantar skin flap. The flap survived well after surgery, and scar was acceptable after 3 and 6 months follow-up.

All the 21 patients underwent bone cement implantation after dead bone osteotomy, among which 19 patients underwent 3D replacement of bone cement implantation within 6 months to 1 year after surgery. Two patients carried bone cement for a long time, one of them was confined to bed for a long time without lower limb weight-bearing because of total paralysis of the lower limbs, and the other refused to undergo 3D prosthesis replacement because of economic problems.

3.2 Typical cases 3.2.1 Case 1

Male, 66 years old, the patient suffered a closed fracture of the left tibia caused by a car accident (Figure 1). After open reduction and internal fixation, the patient had chronic osteomyelitis of the left tibia with repeated soft tissue ulcers for 22 years. The patient had been treated with osteotomy, bone cement filling, external fixator fixation, multiple debridement +VSD in another hospital, but the effect was not good, and the ulcer persisted. Examination after admission: The skin of left calf and foot dorsal is widely pigmented, grey and black, and ulcer formation is widespread on the front and inside of calf, the extent of ulcer involvement is about 10 × 5 cm2, with visible purulent exudation. The external fixator is stable; a small amount of purulent exudation can be seen in the nail hole; the lower leg and the dorsalis of the foot are widely referred to as concave oedema; the skin temperature is higher than the contralateral side; the tenderness is obvious; the acupuncture sensation is decreased; the flexion and extension function of the toe is significantly limited; the ankle joint is stiff; the dorsalis of the foot artery is not touched; and the knee tendon and Achilles tendon reflex of the affected side is not drawn.

Surgical treatment of case 1. A, The patient was admitted for the first debridement. Long-term chronic inflammation of the left leg and foot dorsal skin led to severe local pigmentation, and the wound was covered by VSD. B, After the patient's final debridement, the defect of anterior tibial wound was obvious, with an area of about 11 × 5 cm2, and the bone cement was exposed below. C, The design of the sural nerve trophic level flap, the size is about 18 × 15 cm2, the specific shape is shown in the figure. D, Sural neurotrophic musculocutaneous flap was cut off and transferred to the original wound. Because of local sclerosis caused by long-term inflammation of the surrounding tissue of the original wound, the activity was poor, so part of the flap was removed. E, The flap was transferred to the original wound and fixed with suture. F, Full-thickness skin graft for secondary wounds. G-I, Two weeks after surgery, skin grafting on the skin flap and secondary wounds survived well and the bone cement was not exposed. It was improved after dressing change

3.2.2 Case 2

Male, 64 years old, after external fixation of left tibial open fracture, happened with slow-motion osteomyelitis with anterior tibial soft tissue defect for 1 month (Figure 2). Multiple debridement and VSD treatment were performed in other hospitals. After admission, physical examination showed that many incision scars were healed in the left leg, a soft tissue defect of about 5 × 3 cm2 was visible in the left anterior tibia, and the growth of peripheral tissue granulation was satisfactory.

Surgical treatment of case 2. A, The wound range after detrauma was about 6 × 4 cm2, the tibia was exposed below the wound, and an S-shaped incision was designed on the inner side of the calf. B-D, Soleus muscle was cut and transferred to the defect area of the original wound. E, Full-thickness skin was applied to the soleus muscle flap, and the secondary wound was directly sutured. F, Good skin survival 2 weeks after unpacking

4 DISCUSSION

Slow-going osteomyelitis is more common in adults and young and middle-aged men than post-traumatic osteomyelitis.19 Studies have shown20 that the incidence of deep infection after open fractures in all parts of the body is 2% to 50%. The tibia is the most common site of open fractures and the most common site of slow osteomyelitis.21 The common site of slow osteomyelitis is the lower extremity, while the upper extremity is also susceptible to secondary infection because of traffic accident injuries.22 In our study, 13 patients had chronic osteomyelitis of the tibia, and 1 patient had chronic osteomyelitis of the ulnar and radius caused by car accident, which was consistent with previous research results. Severe soft tissue injury and loss often lead to bone exposure, which is a risk factor for osteomyelitis. According to the degree of soft tissue injury, Gustilo-Anderson classified open long bone fractures into types I, II, and III. The more serious the open fracture, the higher the probability of osteomyelitis.23 Type III open fractures are susceptible to infection because of the lack of fracture coverage, severe wound contamination, improper washing, and fracture instability. Previous studies have shown that S aureus is a common pathogen of chronic osteomyelitis and can be detected in 50% to 75% of patients with chronic osteomyelitis.24 Sheehy et al25 conducted bacterial culture on 166 patients with chronic osteomyelitis, and the results showed that 32% were positive for S aureus, 29% were mixed infection for bacterial culture. Mutluoglu et al26 cultured bone specimens of chronic diabetic osteomyelitis and showed that S aureus was the most common pathogenic bacteria. The second were Staphylococcus epidermis, P aeruginosa, Escherichia coli, Klebsiella pneumoniae, and Proteus. In this study, seven patients were positive for wound bacterial culture, accounting for 33.3% (7/21), among which two patients were S aureus, accounting for 28.6% (2/7), which was consistent with previous studies.

Clinically, thorough debridement is the key to the treatment of chronic osteomyelitis. Previous study27 believe that the key to the treatment of chronic osteomyelitis is the complete removal of necrotic substances. Esterhai et al28 believe that it is difficult to determine the scope of lesion clearance. What both have in common is that the treatment of chronic osteomyelitis requires complete removal of the necrotic and infected tissue, but because of the current clinical experience and technical limitations, it is still difficult to do this completely. At present, most experts and scholars believe that thorough removal should be carried out to remove all suspicious infected objects, including plants, dead bones, and foreign bodies in the infected site, and to remove the surrounding infected soft tissues as large as possible, until fresh bleeding occurs on the bone surface.29, 30 In our study, the typical case 1 had a good recovery after partial resection and suture because of local sclerosis caused by long-term inflammation of the surrounding tissue of the original wound.

Thorough debridement, necrotic tissue removal, multiple operations, and repeated incision will lead to local scar contracture, and long-term slow inflammation will lead to local soft tissue hardening and elasticity reduction, which will lead to local soft tissue coverage difficulties.31 How to use an effective way to achieve soft tissue repair is a more difficult clinical problem in the treatment of slow osteomyelitis, but also the key to the success of treatment. Multiple flap transfer technique in plastic surgery plays an important role in complex wounds of lower limbs. At present, the flaps used to repair soft tissue defects of the leg and foot include plantar medial flaps,32 sural nerve nutrition flaps,33 peroneal artery perforator flaps,34 posterior tibial artery perforator flaps,35 and so on. Masquelet confirmed the possibility of removing the sural nerve axial vascular island flap through latex perfusion, proposed the concept of axial skin flap with cutaneous nerve accompanied by blood vessels, namely “neurotrophic flap,” and applied the reverse sural nerve nutritional vessel island flap in clinical practice and achieved success.36 Sural neurotrophic musculocutaneous flap has been widely used in repairing lower extremity wound defect. In this study, 15 of the 20 patients with chronic osteomyelitis caused by trauma were sutured using sural neurotrophic musculocutaneous flaps. According to the results, patients with neurotrophic musculocutaneous flaps had superior recovery results, which may be based on the rich vascular nerves and resistance to infection of the neurotrophic musculocutaneous flap. Taking into account the convenience of flap extraction, we believe that neurotrophic musculocutaneous flap is the optimal choice for the treatment of patients with osteomyelitis combined with soft tissue defects.

Obviously, postoperative follow-up for chronic osteomyelitis complicated with soft tissue defect is of great significance to evaluate the effect of surgical treatment. At present, we do not have enough follow-up data, and we will follow up and arrange the rehabilitation status of patients in the future. One of the main problems of neurotrophic muscle flaps is the weakening of muscle strength in the donor area because of loss of muscle, which was not evaluate at follow-up in our study, and this is a limitation in the study. In addition, we did not pay enough attention to the aesthetic outcome after treatment while the grafted flaps are generally thick. All of these can be incorporated into evaluation of treatment in the future and may have implications for tissue graft repair techniques.

In conclusion, it is safe and effective to repair the local soft tissue defects in chronic osteomyelitis of adult limbs with plastic surgery tissue transplantation. Early intervention, thorough debridement, removal of necrotic/infected tissues, and selection of appropriate skin flap for effective wound filling and covering are important means to ensure the wound healing of chronic osteomyelitis.