INTRODUCTION

Closed calcaneal fractures are a common trauma seen in orthopedics, accounting for approximately 2% of fractures.1–3 However, previous studies have shown a 31.2% complication rate after closed calcaneal fracture, 25% rate of wound infection, and 21% rate of reoperation due to complications.4 Patients with complications may undergo several debridements, usually resulting in skin defects or even lacunar soft tissue defects that penetrate deep to the bone.5 For small lacunar soft tissue defects, a long period of natural healing is required with careful routine wound care; there is a constant risk of reinfection throughout the healing period.

Conventional treatment includes split-thickness skin graft (STSG), but due to the lack of dermis, weak ductility, hyperpigmentation, scar contracture, inelasticity, and aesthetic problems often occur. If bone is exposed, the STSGs are not usually successful; even if the graft survives, it can significantly contract or fail.

Local flap transfer is often difficult to achieve because there is minimal soft tissue in the heel. Because of the immobility and inelasticity of the skin in this area, it is difficult to transfer local tissue for treatment.6 Although some flap techniques such as peroneal artery perforator flap and reverse sural nerve fasciocutaneous flap have achieved promising therapeutic results in repairing soft tissue defects in the foot and ankle, they require a high level of technical skills and are at risk of necrosis, donor site complications, flap bulking, and stress from shoes.6,7

Dermal substitutes have been widely used in procedures such as chest and abdominal wall reconstruction, facial defects, tendon repair, and urethral reconstruction, and satisfactory results have been obtained.8–11 Animal-derived dermal matrices can be bovine-derived, porcine-derived, or synthetic. However, these matrices may not deliver satisfactory outcomes for difficult-to-heal wounds, ulcerations, or infected wounds. Human-derived acellularized dermal matrices may compensate for such deficiencies, as it not only facilitates the migration of new cells and blood vessels but also inhibits collagen fibers and bacterial colonization given the preservation of the original skin structure and dermal basement membrane.

Accordingly, this study aimed to investigate the clinical effect of a human acellular dermal matrix (HADM) combined with STSG in repairing lacunar soft tissue defects of the lateral heel after calcaneal fracture.

METHODS

This study was approved by the Ethics Committee of the Third Hospital of Hebei Medical University. The Third Hospital of Hebei Medical University is the Orthopedic Treatment Center of Hebei Province, a comprehensive tertiary care hospital with 1,956 beds. All participants gave informed consent to take part in the study. The individuals discussed in this article provided written informed consent to publish their case details and photographs.

Patient Information

Patients were enrolled in this study during their hospitalizations from June 2018 to October 2020. All patients were evaluated separately by two orthopedic surgeons who knew the study’s inclusion and exclusion criteria and postoperative evaluation but were not familiar with the treatment. Patients were invited to participate if both recruiters agreed the patient met the inclusion criteria. Inclusion criteria were wound infection and rupture after internal fixation surgery for calcaneal fractures; after removal of internal fixation for two calcaneal fractures, wound infection and rupture occurred. Exclusion criteria were concomitant calcaneal osteomyelitis; a diagnosis of diabetes, thromboangiitis, or other diseases; or the patient cannot tolerate surgery.

Human Acellular Dermal Matrix

The HADM used in this study is a new type of tissue engineering material developed by Beijing Jieyalaifu Biotechnology Co, Ltd, and is derived from a cadaver. Via biological tissue engineering technology, the epidermis, dermis, and cellular components are completely removed without changing the extracellular matrix structure and basement membrane complexes, so the antigenicity is extremely low and rarely induces host immune reactions. In addition, because the basement membrane complex is retained, the HADM has two levels of tissue: basement membrane and dermis. The basement membrane surface facilitates the migration and colonization of epithelial cells, thus creating favorable conditions for epithelialization of the allogeneic dermis, whereas the dermal surface facilitates the migration of host cells and vascular regeneration. The HADM is designed to be reticulated, which may improve exudate and neovascularization compared with other integrated dermal matrices.12,13

Procedure

Routine preoperative examination focused on infection-related indicators such as C-reactive protein, procalcitonin, and bacterial culture of wound secretions. Lower limb vascular ultrasound or computed tomography angiography was performed to evaluate extremity blood supply. Intravenous antibiotics were used prophylactically according to inflammatory indicators.

After intraspinal anesthesia, wounds were cleaned and sterilized and then infected, necrotic, and inactive tissue around the wound and deep tissue were removed, working from superficial to the deeper layers. Upon reaching to the bone surface, the surgeon drilled holes on the bone surface until blood arose on the exposed surface. The surgical area was rinsed with 0.9% sodium chloride solution. Meanwhile, the HADM was soaked with 0.9% sodium chloride solution and trimmed into appropriate shapes according to the size of the wound. The remaining HADM was snipped into uneven blocks, and then the lacunar defect was filled uniformly, layer by layer, and the outermost surface was covered with a complete wound-sized layer of HADM. The filled wound was covered to keep the scaffold structure intact. The same surgeon performed all of the procedures.

An STSG was obtained from the front of the patient’s thigh through a skin extractor. Then, the skin graft was sutured onto the wound surface, and the skin graft surface was fixed via negative-pressure wound therapy (NPWT). The NPWT was replaced 7 days after surgery and removed 14 days after surgery so providers could observe the survival of the skin graft.

Follow-up

After surgery, regular outpatient reviews were conducted for more than 6 months. The two orthopedic surgeons who recruited patients also assessed outcomes. The main outcome measures were skin graft survival and donor site recovery, including scar color (ie, pink, grey, white, black), hyperplasia size and texture, healing time, and reoperation. Healing was defined as the skin graft has a rosy color, is closely adhered to the subcutaneous area and cannot be pushed forward, is nonfloating, and has no exudation. Skin flexibility and pinch ability refer to good skin elasticity and partial stretchability.

RESULTS

Eleven patients were enrolled, including seven men and four women. Their ages ranged from 12 to 65 years, with an average of 31.6 years. Three patients were referred for infection after internal fixation or removal of internal fixation in other departments of the hospital, and eight patients were transferred from other hospitals (Tables 1 and 2).

Table 1 - PATIENT DEMOGRAPHICS Patient No. Sex Age, y Cause of Calcaneal Fracture Comorbidities Smoker 1 Male 37 Fall None Yes 2 Male 62 Traffic accident Hypertension, diabetes Yes 3 Male 48 Fall Gout No 4 Female 43 Traffic accident None No 5 Female 51 Traffic accident Hypertension No 6 Male 53 Crushing injury None Yes 7 Male 46 Crushing injury Hypertension Yes 8 Female 65 Traffic accident Hypertension, hyperlipemia No 9 Male 45 Fall Depression Yes 10 Female 55 Fall None Yes 11 Male 56 Traffic accident Diabetes No
Table 2 - CLINICAL DETAILS Patient Extremity Wound Size, cm Osteomyelitis Debridements Prior to Surgery, n Skin Grafts 1 Left 9.1 × 0.75 No 3 1 2 Left 6.5 × 0.87 Yes 5 0 3 Right 0.8 × 1 Yes 2 0 4 Left 1 × 0.9 No 1 0 5 Right 8 × 0.85 No 3 1 6 Right 6.7 × 1.6 No 4 1 7 Left 7.3 × 1.7 No 3 1 8 Right 9 × 2.4 No 6 0 9 Left 6.5 × 1.6 No 2 2 10 Right 7.1 × 2.5 No 2 0 11 Left 6.6 × 1.65 Yes 5 2

Of the 11 patients, 8 patients achieved complete wound healing after debridement and HADM + STSG. In three patients, partial necrosis occurred at the edge of the skin graft area, but these wounds healed after conventional wound nursing. Evaluations at 6 and 12 months after surgery showed that all patients had good wound healing, no local scars, and no obvious pigmentation or scar formation in donor sites. Skin durability and pinch ability were good. The average time to heal was 37.5 days (range, 24-43 days; Table 3). None of the cases required a reoperation or rehospitalization.

Patient No. Debridements, n Survival of Skin Graft Healing Time, d 1 2 Whole 24 2 2 Major 41 3 1 Whole 39 4 1 Whole 42 5 1 Major 34 6 2 Major 43 7 1 Whole 40 8 2 Major 37 9 1 Whole 42 10 1 Whole 33 11 2 Whole 38
Case Exemplar

A 37-year-old man was referred to the authors’ facility after receiving treatment for calcaneal fracture with plate internal fixation through a lateral extensile approach on the lateral side of the heel at a district hospital 3 years prior. Internal fixation was removed on the original incision 18 months after the operation. A postoperative hematoma formed in the wound, and the wound did not heal and became infected after debridement of the hematoma. After repeated debridement, a skin defect of 8 × 2 cm2 was formed, and yellow and white secretions and necrotic tissue could be seen on the wound surface (Figure 1).

Figure 1.:

WOUND CONDITION OF PATIENT ON ADMISSION

Routine examination was conducted, and intravenous antibiotic anti-infection treatment was given in hospital (30 minutes before surgery and at 2 days postsurgery). After infection was improved, the necrotic tissue was completely removed and the wound surface was covered with NPWT. One week later, the NPWT was removed. New granulation tissue had formed in the wound surface, with few yellow and white necrotic tissues apparent in the middle of the wound. After the necrotic tissue thoroughly degenerated, a lacunar defect about 3 × 1 cm formed that penetrated deeply into the bone surface (Figure 2). Thin layers of bone were chiseled off, and holes were drilled into the bone surface to extract fresh blood from the bone marrow cavity and allow nutrients to enter the HADM and skin graft.

Figure 2.:

DEBRIDEMENT OF THE WOUND, LACUNAR DEFECT IS VISIBLE

The HADM was soaked in 0.9% sodium chloride solution and then cut up and packed in the lacunar cavity (Figure 3). The HADM was trimmed to match the wound, and the STSG was placed to cover the HADM (Figure 4). Subsequently, NPWT was placed. After surgery, the patient was given intravenous antibiotics and standard wound care. The NPWT was replaced 7 days after surgery and removed 14 days after surgery to observe the survival of the skin graft (Figure 5). There were some areas of black necrosis at the edge of the skin graft area, but the wound healed after wound care without reoperation (Figure 6).

Figure 3.:

THE HUMAN ACELLULAR DERMAL MATRIX IS CUT AND FILLED INTO THE LACUNAR DEFECT

Figure 4.:

AFTER COVERING THE WOUND WITH HUMAN ACELLULAR DERMAL MATRIX

Figure 5.:

THE NEGATIVE-PRESSURE WOUND THERAPY WAS REMOVED 14 DAYS POSTOPERATION, AND NECROSIS OF THE SKIN GRAFT WAS VISIBLE

Figure 6.:

THE WOUND HEALED AT 2-MONTH POSTOPERATIVE FOLLOW-UP

DISCUSSION

Wound infection is one of the most common complications after internal fixation of calcaneal fractures.14 Influencing factors are related to (1) patient demographics such as age, body mass index, history of smoking, drug use, and diabetes; (2) the injury, including the cause of injury, type of fracture, and internal fixation; (3) the surgical approach: a lateral extensile approach often destroys the peroneal perforator artery, resulting in the destruction of the skin blood supply, and the soft tissue around the heel bone is thus vulnerable to extensive detachment during surgery, which damages the blood supply of the heel and the flap around the incision, eventually leading to interruption of the skin blood supply and incision complications;15 (4) the longer a tourniquet is used, the longer the limb ischemia and hypoxia, and the relaxation of congestion and swelling, secondary microcirculatory disorders and tissue damage due to ischemia-reperfusion injury, which are not conducive to incision healing; and (5) other factors such as the surgeon’s experience, surgical time, OR environment, and so forth.

Selection of Repair Methods

For small, superficial infections, most can heal with debridement and wound care. For larger areas, STSGs are feasible. In contrast, for patients with more soft tissue defects and tendon or bone exposure, flap repair is recommended. However, some patients with lacunar soft defects that remain after repetitive debridement are more difficult to heal and require consultation with an experienced surgeon. Conventional wound care or skin grafting results may not be satisfactory. Flap repair also has the disadvantages of donor site complication, flap bulking, and vulnerability to shoe wear. Currently, commonly used flaps include sural nerve flap, posterior tibial artery perforator flap, and free flaps such as anterolateral femoral flap and latissimus dorsi flap.16

Advantages of HADM in Combination with Simultaneous Implants

Numerous studies have confirmed the effectiveness and safety of HADM in the treatment of burns and trauma and oral, breast, and urologic surgery. Pontell et al17 compared reverse sural fasciocutaneous flaps combined with skin grafting and reverse sural fasciocutaneous flaps combined with ADM and NPWT in the treatment of complicated soft tissue defects in the foot or ankle and demonstrated a significant reduction in overall wound healing time and reoperation rate. Acevedo et al18 applied HADM to fill defects to enhance tendon healing strength as well as tension and fusion characteristics between the implant and the original recipient tissue in rotator cuff injury and biceps rupture.

Patients have achieved significant pain relief and favorable function with this technology. Bertasi et al8 applied HADM to repair Achilles tendon ruptures and demonstrated excellent infiltration of ADM in the paratendon with no inflammatory response (assessed via immunohistochemistry). In addition, intensive revascularization and cellularization were observed on the interface between the ADM and the paratendon, demonstrating the superior tissue fusion properties of the scaffold. Yao et al19 applied HADM to the area of the bone defect after resection of the trapezium bone in the first carpal metacarpal arthritis and showed less space loss on radiologic imaging 6 months after surgery, a significant improvement in postoperative pain scores and grip strength, and no complications such as rejection or infection.

This study was designed to repair lacunar soft tissue defects using HADM + STSG. There are several advantages of this approach, primarily the HADM itself, which includes the epidermis and cellular components from the dermis while preserving the three-dimensional spatial structure composed of elastin and collagen in the dermis. Not only does it have a very low rate of rejection, providing revascularization and fibrosis, but it also delays granulation tissue neogenesis, thus promoting the migration of epithelial cells and fibroblasts and providing a well-defined scaffold structure. Further, the HADM preserves the excellent mechanical properties and three-dimensional spatial structure of the human dermis, which can fill the defect and act as a soft tissue scaffold to promote vascular regeneration and the formation of connective tissue and lymphatic system. This facilitates the regeneration and repair of the defective tissue. In addition, covering the wound with HADM not only reduces the loss of tissue fluid and plasma protein, but also reduces bacterial invasion, prevents infection, and restores the imbalanced microenvironment to physiologic equilibrium to promote healing.20

Another advantage is that simultaneous implantation of the STSG on the surface of the HADM reconstructs both the epidermal and “dermal scaffold” structures. The preserved extracellular matrix structure and basement membrane complex contain elastin and collagen, which can reduce skin tension, maintain the appearance characteristics of the implanted area, increase the elasticity of the new skin, and provide mechanical protection to the body. The implantation of HADM results in less proliferation of collagen fibers, which can weaken scarring and reduce contracture production, both of which are important for aesthetic and functional results.21 Finally, compared with flap surgery, this method has several advantages, including simple technique, short operation time, less invasion of the donor area, less swollen appearance, and ease of use.

The HADM is compatible with various body tissues and provides good scaffolding, and the matrix is recognized by the host cells and completely absorbed by the host cells after implantation without rejection and inflammatory reactions.22,23

Negative-pressure wound therapy is a wound repair modality that can be used in complex wounds and even severely infected wounds because of its good histocompatibility and continuous suction properties, which can reduce debridements, pain, and hospitalization time.24–27 Further, NPWT increases local blood flow, reduces hematoma and edema, reduces bacterial colonization, enhances cellular activity, and improves granulation and re-epithelialization.17 When applied to the implant area, the continuous negative pressure provides a stable pressure with uniform distribution of the matrix, thus reducing shear and providing positive wound adhesion. Using exudate drainage reduces hematoma and edema under the implant, reduces the risk of infection, and provides uniform and continuous pressure and stability compared with traditional gauze fixation, making it easy to change and reducing patient pain.28

However, there are some drawbacks to the HADM. Because of its inherent lack of blood flow and poor resistance to infection, it requires enhanced preoperative conditions such as blood flow at the defect and infection control. Further, for big soft tissue defects, especially in patients with combined bone and tendon exposure, the repair effect is inferior to that of flaps. Finally, HADM is expensive, which increases the burden on patients.

Limitations

This study included a limited number of cases and no control group. Further randomized controlled studies will be designed to include more cases and longer follow-up periods. In the future, cases with special conditions, such as diabetes, thromboangiitis obliterans, and other refractory wounds, will be added to evaluate the application range of acellular dermal materials.

CONCLUSIONS

This HADM combined with STSG and NPWT may be a safe and effective treatment for lateral heel cavity soft tissue defects after calcaneal fracture.

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