Long-Term Metabolic Assessment of Cryopreserved Sternal Allograft: A Case Series.

BACKGROUND: Sternal resection and reconstruction with cryopreserved allografts provides a safe alternative to traditional methods of anterior chest wall reconstruction. Despite favorable results, successful integration of the graft sternum has never been demonstrated owing to the invasiveness of bone biopsy. We describe our experience of using 18F-sodium fluoride positron emission tomography/computed tomography scans as a noninvasive method of evaluating graft integration. METHODS: Seven patients underwent surgery and radiologic follow-up. Surgical indications were sternal metastases (n = 5) and sternal dehiscence (n = 2). Sternal reconstruction was performed using a cryopreserved cadaveric sternal allograft fixed in place with titanium plates and screws. Follow-up with 18F-sodium fluoride positron emission tomography/computed tomography scans was performed at 1 and 2 years after surgery. RESULTS: Three patients underwent total sternectomy. Two underwent partial upper sternectomy involving the manubrium, clavicle (1 patient only), and upper sternal body; and 2 had partial sternectomy of the sternal body and xiphoid process. Focal tracer accumulation occurred at the junctions between native bone and graft bone. The median maximum standardized uptake value at 1 year was 16.8 (range, 11.2 to 37.9; interquartile range, 13.6 to 19.4), and at 2 years it was 10.8 (range, 6.1 to 30.2; interquartile range, 8.9 to 15.1). In 6 cases accumulation was lower at the second scan, whereas in 1 patient the accumulation was higher at the second scan. CONCLUSIONS: Sternal reconstruction with cryopreserved allograft is safe and well tolerated. The 18F-sodium fluoride positron emission tomography/computed tomography scans are a useful and promising noninvasive method of demonstrating the metabolic activity of the graft and its incorporation into the host skeleton during follow-up.

Indications and Results of Sternal Allograft Transplantation: Learning From a Worldwide Experience.

BACKGROUND: Reconstruction of the anterior chest wall defect after sternectomy is a challenge for cardiothoracic surgeons. In 2010, the Padua group published the first case of cadaveric sternum transplantation after sternectomy. This multicenter study reports the clinical indications and early and long-term results of sternal chondral allograft transplantation. METHODS: This is a retrospective multicenter study from 7 academic centers. We collected demographic data, surgical indications, technical details, and early postoperative results. The complications, long-term stability, and tolerance of the allografts were also analyzed. RESULTS: Between January 2008 and December 2019, 58 patients underwent sternectomy followed by reconstruction using cadaveric-cryopreserved sternochondral allografts. Thirty-two patients were male, median age 63.5 years (interquartile range, 50-72 years). Indications for sternectomy were secondary sternal tumors (n = 13), primary sternal tumors (n = 15), and nonneoplastic disease (n = 30). Thirty patients underwent total sternectomy, 16 lower-body sternectomy, and 12 upper-body manubrium resection. The 30-day mortality was 5%; overall morbidity was 31%. Six early reoperations were necessary because of bleeding (n = 1), titanium plate dislocation (n = 1), and resuture of the skin in the lower part of the incision (n = 4). Overall, 5-year survival was 74%. In all the survived patients, the reconstructions were stable and free from mechanical or infective complications. CONCLUSIONS: The main indications for sternal allograft implantation were complex poststernotomy dehiscence followed by primary or secondary tumor involvement of the sternum. The collected results demonstrate that sternochondral allograft transplantation is a safe and effective method in reconstructing the anterior chest wall after sternectomy. Further studies to demonstrate the integration of the bone grafts into the patients' sternal wall will be made.

Sternal allograft transplantation for anterior chest wall reconstruction after sternectomy.

The reconstruction of the anterior chest wall after sternectomy for cancer or after mediastinitis is still a challenging procedure for the thoracic surgeon. Different surgical techniques and materials have been used for anterior chest wall reconstruction, but none of them is yet considered to be the gold standard.  In this video tutorial, we report on our experience of using a sternal allograft for reconstruction of the anterior chest wall. Sternal allografts offer the same advantages as bone autografts and obviously are perfectly shaped for sternal replacement. They are simple to trim and to fix to the chest wall and, unlike autografts, do not require the patient to undergo an additional incision and procedure for harvesting the bone.

The autogenous graft versus transport distraction osteogenesis for reconstruction of the ramus-condyle unit: a prospective comparative study.

This study aimed to compare the joint function and morphology achieved following condylar reconstruction using sternoclavicular grafts (SCG) versus transport distraction osteogenesis (TDO) in temporomandibular joint (TMJ) ankylosis patients. Twenty-two patients with TMJ ankylosis underwent TMJ reconstruction with SCG or TDO (n=11 each). Radiographic and clinical evaluations were performed at 1 week and at 1, 3, and 6 months post-surgery. Clinical criteria examined included the duration of surgery, mean postoperative mouth opening, excursive jaw movements, and pain scores. The radiographic evaluation 6 months postoperatively (computed tomography) included subjective assessment of joint morphology and measurements of the mean condylar height, width achieved, and amount of condylar resorption. The χ2 test and Student t-test were used to compare qualitative and quantitative variables, respectively. Similar mean mouth opening (SCG=31.8mm, TDO=32.1mm at 6 months), excursive movements, and pain scores were observed in the two groups throughout follow-up. Mean condylar resorption was significantly greater in the TDO group (TDO=7.0mm, SCG=2.7mm; P=0.005). The duration of reconstruction surgery was greater in the SCG group (P=0.035). A greater incidence of complications was observed with TDO. In conclusion, based on the protocols used in this study, SCGs are superior to TDO in terms of condylar morphology, stability, and surgical safety.

Novel technique for harvesting the sternoclavicular graft.

PURPOSE: Originally introduced for mandibular reconstruction more than 40 years ago, the sternoclavicular graft (SCG) has gained widespread popularity for the reconstruction of the ramus-condyle unit (RCU) owing to its anatomic and histological likeness to the normal mandibular condyle. Conventional longitudinal osteotomy design for its harvest has been fraught with considerable complications at the donor site including fracture clavicle and major neurovascular injury. In an attempt to alleviate these ill effects, a new technique for procuring the sternoclavicular graft is presented. MATERIAL AND METHODS: A split-thickness cortico-cancellous graft was harvested form the sternal end of the clavicle along with the articular disk with the osteotomy cut oriented parallel to the coronal plane, with limited soft tissue dissection. Donor site complications were assessed in terms of incidence of clavicle fracture, neurovascular injury, pleural tear and radiographic healing as seen in the six-month postoperative chest radiograph. RESULTS: 17 patients suffering from unilateral temporomandibular joint ankylosis underwent SCG harvesting for RCU reconstruction following osteoarthrectomy. No adverse events were seen in the intra- and post-operative period in any patient and satisfactory radiographic osseous healing was observed after six months. CONCLUSION: The proposed harvest technique for SCG results in reduced donor site morbidity and favourable healing and greater patient comfort.

Safety and Effectiveness of Cadaveric Allograft Sternochondral Replacement After Sternectomy: A New Tool for the Reconstruction of Anterior Chest Wall.

BACKGROUND: Surgical excision with wide margins, prevention of respiratory impairment, and protection of surrounding organs are primary goals in resection and reconstruction of the chest wall. We describe our experience of the use of cadaveric cryopreserved sternal allograft. METHODS: Eighteen patients underwent surgery. Indications for sternectomy were sternal metastases (n = 9), primary chondrosarcoma (n = 4), sternal dehiscence (n = 2), soft tissue sarcoma (n = 1), malignant solitary fibrous tumor (n = 1), and direct involvement of thymic carcinoma (n = 1). The defect was reconstructed using a cadaveric sternal allograft harvested aseptically, treated with antibiotic solution, and cryopreserved (-80°C). The graft was tailored to fit the defect and fixed in place with titanium plates and screws. RESULTS: Four patients underwent a total sternectomy, 8 a partial lower sternectomy, and 6 a partial upper sternectomy. In 14 patients, muscle flaps were positioned to cover the graft. During the postoperative course, 1 patient died of pulmonary embolism, 1 had systemic Candida infection, and 1 had surgical revision for bleeding at the site of muscle flap. One patient required removal of a screw on the clavicle 4 months after operation because of partial dislocation. At a median follow-up of 36 months, neither infection nor rejection of the graft occurred; 13 patients are alive without disease, and 4 patients had died. None had local tumor relapse. CONCLUSIONS: Sternal replacement with cadaveric allograft is safe and effective, providing optimal stability of the chest wall and protection of the surrounding organs, even after extensive chest wall resections. The allograft was biologically well tolerated, allowing a perfect integration into the host.

[Transplantation of allogeneic bone graft in the therapy of massive post-sternotomy defects - 6 years of experience with the method]. / Transplantace allogenního kostního stepu v lécbe rozsáhlých post-sternotomických defektu - 6 let zkuseností s metodou.

INTRODUCTION: Early complications due to deep sternal wound infection pose a serious problem in cardiac surgery, with an up to 40% risk of mortality. Massive loss of sternum bone tissue and adjacent ribs results in major chest wall instability difficult to resolve using classical AO osteosynthesis procedures, causing respiratory insufficiency making the disconnection from artificial pulmonary ventilation difficult, and additional defects of soft tissue healing. Based on orthopaedic experience with bone defect replacement, we used the allogeneic bone graft method to reconstruct the chest wall. METHODS: In the period of 20112015 we performed the transplantation of an allogeneic bone graft in 13 patients. In 10 cases, an allograft of the sternum was used, in one case an allograft of the calva bone and in two cases the crushed spongy bone was used. After primary cardiac surgery, a massive post-sternotomy defect of the chest wall developed in all the 13 patients due to deep sternal infection and osteomyelitis of the sternum and adjacent ribs. Vacuum wound drainage was applied in the treatment of all the patients. To stabilize the chest and the graft, transverse titanium plates were used, fixed using bicortical screws. The bone allograft was prepared by the official Tissue Centre. Crushed allogeneic spongy bone was applied to reinforce the line of contact of the graft and the edges of the residual skeleton. In 12 cases, the soft tissue was closed by direct suture of mobilized pectoral flaps. In one case, V-Y transposition of the pectoral flap was performed. RESULTS: In 8 cases, healing of the reconstructed chest wall occurred without further complications. In 4 cases, additional re-suture of soft tissues and skin in the lower pole of the wound was needed while the patients were still in the hospital. However, excellent chest wall stability along with adjustment of respiratory insufficiency and a very good cosmetic effect in the wound were achieved in all the 12 cases. In two cases, explantation of the plates was required. In one case, severe concomitant complications and no healing of the wound resulted in death within half a year after the reconstruction. The median follow-up period of all patients in the series was 21 months (136). In 5 cooperating patients, scintigraphy of the chest wall was performed repeatedly during the follow-up period showing a high healing activity of the graft and particularly of the crushed spongy bone. CONCLUSION: Our existing results show that allogeneic bone graft transplantation is a promising and easily applied method in the management of serious tissue loss in sternal dehiscence with favourable functional and cosmetic effects.Key words: sternotomy deep sternal wound infection massive post-sternotomy defect allogeneic bone graft.

Clinical Study of Allogeneic Graft Reconstruction for Sternum Tumor.

OBJECTIVES: This paper aimed to study the feasibility, the surgical methodology, and technique for reconstruction using allogeneic sternal graft after sternum tumor resection. MATERIALS AND METHODS: Three patients (2 men and 1 woman, aged 19, 44, and 52) with primary sternum malignant tumor were admitted from January 2008 to December 2010 to the Second Hospital of Shandong University, Jinan, China. We conducted subtotal resection of the sternum and simultaneous reconstruction with allogeneic sternal graft. Allogeneic sternum was frozen beforehand; the scope of removal was 2 cm away from the lesion. Transplanted allogeneic sternum was fixed using steel wire and residual cavity was filled with the greater omentum. RESULTS: Three patients recovered without major complication and were discharged from the hospital with successful operation and satisfactory results. They were followed-up for 6 months to 2 years, no tumor relapse or any obvious rejection were found. CONCLUSIONS: The freezing allogeneic sternum can be used as a substitute for reconstruction after sternum tumor resection.

Sternohyoid flap for facial reanimation: a comprehensive preclinical evaluation of a novel technique.

IMPORTANCE: Neuromuscular reanimation of the face provides the correct specific neural functional input and thereby prevents synkinesis. Unfortunately, this ideal situation is rarely encountered in the clinical setting. OBJECTIVES: To assess the technical feasibility of and define the surgical procedure for harvesting the sternohyoid muscle as a novel free flap for use in facial reanimation indications. DESIGN, SETTING, AND PARTICIPANTS: Fresh, postmortem, nonfixed cadavers were used to define the anatomy and perform the flap harvest procedures. Twenty-four flap harvests were performed. Angiography was performed on the pedicle of the harvested flaps to assess potential flap perfusion. Adenosine triphosphatase staining was performed on the muscle specimens to establish fiber type. MAIN OUTCOME MEASURES: The harvest technique, pedicle (arterial or venous), nerve length, and flap geometry parameters were characterized. RESULTS: The sternohyoid muscle was found to be reliably vascularized by the superior thyroid artery in all cases with an appropriate arterial and venous pedicle for vascular anastomosis. The mean arterial (5.5 cm) and venous (5.9 cm) pedicle lengths are comparable with gracilis flaps. The mean motor nerve length was 10.7 cm. The inclusion of the hyoid bone allows rigid fixation, and the muscle size, fiber type, and volume profiles all compare favorably to the gracilis flap for use in the indication of facial reanimation. Mock surgical procedures were performed to define inset parameters. This flap potentially allows single-stage cross-facial neurorrhaphies to be performed. CONCLUSIONS AND RELEVANCE: This is the first article, to our knowledge, of the sternohyoid muscle as a potential donor site for free-tissue transfer. This muscle has a predictable vascular pedicle and neural innervation along with size and fiber type parameters that make it an ideal potential free flap for facial reanimation. LEVEL OF EVIDENCE: NA.

Sternal resection and reconstruction for local recurrence of breast cancer using the sternal allograft transplantation technique.

Sternal involvement in patients with breast cancer is relatively rare and its treatment is still controversial. Surgery is usually indicated in cases of single metastases in a multimodality protocol. Partial or complete sternectomy associated or not with the resection of surrounding tissues is the technique of choice to obtain safety margins and radical treatment of the disease. The most challenging part of the operation is the reconstruction of the anterior chest wall in order to avoid secondary complications and respiratory failure. In the last few years, different techniques and materials have been used to reconstruct the sternum. We report our experience in two patients with recurrent breast cancer using the sternal allograft technique to replace the sternum after partial sternectomy. The use of a sternal-allograft provides excellent functional and cosmetic results without complications during the follow-up period. The implantation technique is simple and reproducible.

Composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin allotransplantation model of bone marrow transplantation.

Cellular and vascularized bone marrow cells have been used to induce donor-specific chimerism in various models of composite tissue allotransplantation. Although thymus transplantation has been reported in the literature, the effect of thymus transplantation on chimerism levels in vascularized bone containing composite tissue allotransplantation has not been reported. In this study, a new method for composite vascularized sternal bone marrow transplant model is descried that can be applied to augment chimerism after transplantation. A total of seven composite osseomusculocutaneous sternum, ribs, thymus, pectoralis muscles, and skin transplantations were performed in two groups. The first group (n = 5) was designed as an allotransplantation group and the second group (n = 2) was designed as an isotransplantation group. Composite osseomusculocutaneous sternum, ribs, thymus, and pectoralis muscles allografts were harvested on the common carotid artery and external jugular vein and a heterotopic transplantation was performed to the inguinal region of the recipient rat. Cyclosporine A monotherapy was administered in order to prevent acute and chronic allograft rejection. Animals sacrificed when any sign of rejection occurred. The longest survival was 156 day post-transplant. Assessment of bone marrow cells within sternum bone component and flow cytometry analysis of donor-specific chimerism in the peripheral blood of recipients were evaluated. Our results showed that this composite allograft carried 7.5 × 10(6) of viable hematopoietic cells within the sternum component. At day 7 post-transplant chimerism was developed in T-cell population and mean level was assessed at 2.65% for RT1(n) /CD4 and at 1.0% for RT1(n) /CD8. In this study, a new osseomusculocutaneous sternum, ribs, thymus, pectoralis muscle, and skin allotransplantation model is reported which can be used to augment hematopoietic activity for chimerism induction after transplantation.

An alternative technique for anterior chest wall reconstruction: the sternal allograft transplantation.

OBJECTIVES: Sternal resection is indicated for a variety of pathological conditions, mainly neoplastic or related to sternotomy complications. Resection of the sternum generally leaves a large chest-wall defect, and reconstruction is thus the most difficult part of the operation. Correct stabilization of the anterior chest wall is very important to avoid secondary complications and respiratory failure. In the last few years, different technical solutions have been used to reconstruct the sternum. We describe our technique using a sternal allograft to reconstruct the anterior chest wall after partial or complete sternal resection. METHODS: Between June 2010 and February 2012, four patients underwent sternectomy followed by anterior chest wall reconstruction using sternal allograft. The sternal allograft was harvested from a multitissue donor following Italian legislation for tissue donation. Three patients had neoplastic involvement of the sternum, and one had a complete sternal defect as a complication of a cardiac operation. RESULTS: We had no operative mortality. Three patients underwent partial sternal transplantation, and one underwent total sternal replacement. We had no postoperative respiratory insufficiency, infections or mechanical failure of the reconstructions. The respiratory function was preserved in all patients. The follow-up period was free from complications related to the sternal allograft implantation. CONCLUSIONS: The technique of sternal allograft transplantation is simple, reproducible and provides excellent functional and cosmetic results. Further studies including a larger number of patients are needed to understand the biology of the allograft and the long-term results of this technique.

Impregnation of bone chips with alendronate and cefazolin, combined with demineralized bone matrix: a bone chamber study in goats.

BACKGROUND: Bone grafts from bone banks might be mixed with bisphosphonates to inhibit the osteoclastic response. This inhibition prevents the osteoclasts to resorb the allograft bone before new bone has been formed by the osteoblasts, which might prevent instability. Since bisphosphonates may not only inhibit osteoclasts, but also osteoblasts and thus bone formation, we studied different bisphosphonate concentrations combined with allograft bone. We investigated whether locally applied alendronate has an optimum dose with respect to bone resorption and formation. Further, we questioned whether the addition of demineralized bone matrix (DBM), would stimulate bone formation. Finally, we studied the effect of high levels of antibiotics on bone allograft healing, since mixing allograft bone with antibiotics might reduce the infection risk. METHODS: 25 goats received eight bone conduction chambers in the cortical bone of the proximal medial tibia. Five concentrations of alendronate (0, 0.5 mg/mL, 1 mg/mL, 2 mg/mL, and 10 mg/mL) were tested in combination with allograft bone and supplemented with cefazolin (200 µg/mL). Allograft not supplemented with alendronate and cefazolin served as control. In addition, allograft mixed with demineralized bone matrix, with and without alendronate, was tested. After 12 weeks, graft bone area and new bone area were determined with manual point counting. RESULTS: Graft resorption decreased significantly (p < 0.001) with increasing alendronate concentration. The area of new bone in the 1 mg/mL alendronate group was significantly (p = 0.002) higher when compared to the 10 mg/mL group. No differences could be observed between the group without alendronate, but with demineralized bone, and the control groups. CONCLUSIONS: A dose-response relationship for local application of alendronate has been shown in this study. Most new bone was present at 1 mg/mL alendronate. Local application of cefazolin had no effect on bone remodelling.

Allogenic sternal transplant after sternectomy for metastasis of ovarian carcinoma.

Sternal metastasis from ovarian carcinoma is extremely rare. We report a case of a young woman in whom a single metastasis at the level of the upper portion of the sternum developed. Surgical excision of the sternum was performed with replacement by a sternal allograft stabilized by titanium plates and transosseous high-tension sutures. With this simple and reproducible technique, we obtained a stable and dynamic reconstruction of the sternoclavicular joints and shoulder girdle. The use of a sternal allograft provides excellent functional and cosmetic results. The implantation technique is simple and reproducible.

Chest wall repair with engineered fetal bone grafts: an efficacy analysis in an autologous leporine model.

PURPOSE: We sought to compare the efficacy of engineered fetal bone grafts with acellular constructs in an autologous model of chest wall repair. METHODS: Rabbits (n = 10) with a full-thickness sternal defect were equally divided in 2 groups based on how the defect was repaired, namely, either with an autologous bone construct engineered with amniotic mesenchymal stem cells on a nanofibrous scaffold or a size-matched identical scaffold with no cells. Animals were killed at comparable time-points 18 to 20 weeks postimplantation for multiple analyses. RESULTS: Gross evidence of nonunion confirmed by micro-computed tomography scanning was present in 3 (60%) of 5 of the acellular implants but in no engineered grafts. Histology confirmed the presence of bone in both types of repair, albeit seemingly less robust in the acellular grafts. Mineral density in vivo was significantly higher in engineered grafts than in acellular ones, with more variability among the latter. There was no difference in alkaline phosphatase activity between the groups. CONCLUSIONS: Chest wall repair with an autologous osseous graft engineered with amniotic mesenchymal stem cells leads to improved and more consistent outcomes in the midterm when compared with an equivalent acellular prosthetic repair in a leporine model. Amniotic fluid-derived engineered bone may become a practical alternative for perinatal chest wall reconstruction.

No effect of ketoprofen and meloxicam on bone graft ingrowth: a bone chamber study in goats.

BACKGROUND AND PURPOSE: There is increasing awareness that non-steroidal anti-inflammatory drugs (NSAIDs), and especially the cyclooxygenase-2 (COX-2) selective ones, may retard bone healing. We have used NSAIDs (indomethacin for at least 7 days) to prevent heterotopic ossification after acetabular reconstructions using impacted bone grafts. The long-term clinical results have been satisfying, making it difficult to believe that there is an important negative effect of NSAIDs on graft incorporation. We studied the effect of two different NSAIDs on bone and tissue ingrowth in a bone chamber model in goats, using autograft, rinsed allograft, and allograft that had been rinsed and subsequently irradiated. METHODS: 9 goats received no NSAIDs, 9 received ketoprofen, and 9 received meloxicam--all for 6 weeks. In each goat 6 bone chambers were implanted: 2 filled with autograft, 2 with rinsed allograft, and 2 with allograft that had been rinsed and irradiated. The amount of bone ingrowth and total tissue ingrowth was compared between the groups. RESULTS: There were no statistically significant differences in bone ingrowth between the different groups. Also, no differences in bone ingrowth were found with respect to the type of graft used. Furthermore, there was no statistically significant difference in the total amount of ingrowth of fibrous tissue between the treatment groups. INTERPRETATION: No differences in bone ingrowth in titanium bone chambers could be detected with both ketoprofen and meloxicam compared to untreated control animals. This confirms our hypothesis that the effect of NSAIDs on the incorporation and ingrowth of bone graft is limited.

Impact of donor bone marrow on survival of composite tissue allografts.

Composite tissue allotransplants (CTA) involves transplantation of various tissues including vessels, nerves, skin, and immune cells and bears significant antigenic load. Different immunosuppressive protocols are used for experimental and clinical CTA. Immunosuppressive agents maintain survival of the different components of composite tissue allografts. However, the potential side effects of chronic immunosuppression currently limit the widespread application of CTA transplants. Bone marrow therapy in many tolerance induction protocols therefore provides a guide to reaching the target of permanent immunotolerance. Multiple studies suggest that bone marrow is immunomodulatory and may facilitate allograft acceptance. In this review, bone marrow-based therapy protocols of experimental and clinical models are presented in composite tissue transplantation.

Irradiation has no effect on the incorporation of impacted morselized bone: a bone chamber study in goats.

BACKGROUND: Gamma irradiation has been widely used for sterilization of bone allografts. However, gamma irradiation alters proteins. This is favorable when it reduces immunogenicity, but is undesirable when osteoinductive proteins are damaged. Although the effect of gamma irradiation on BMPs has been studied, the effect of irradiation on the process of incorporation of morselized bone chips remains unclear. We studied the effects of sterilization by gamma irradiation on the incorporation of impacted morselized allografts. METHODS: Bone chambers with impacted allografts, rinsed impacted allografts, allografts that were rinsed and subsequently irradiated, and an empty control were implanted in proximal medial tibiae of goats. Incorporation was evaluated using histology and histomorphometry. RESULTS: Histology revealed evidence of bone graft incorporation, which proceeded in a similar way in unprocessed, rinsed, and both rinsed and irradiated bone grafts. After 12 weeks, no difference in bone and tissue ingrowth was found between the unprocessed, the rinsed, and the rinsed and subsequently irradiated allografts. The amount of unresorbed graft remnant was highest in the unprocessed bone grafts. INTERPRETATION: We conclude that sterilization with gamma irradiation does not influence the incorporation of impacted rinsed bone allografts.