Esther Vögelin

Healing of a critical-sized defect in the rat femur with use of a vascularized periosteal flap, a biodegradable matrix, and bone morphogenetic protein

BACKGROUND The purpose of this study was to evaluate the osseous healing of a critical-sized femoral defect in a rat model with use of recombinant human bone morphogenetic protein-2 (rhBMP-2), a matrix fabricated of D,D-L,L-polylactic and hyaluronan acid (OPLA-HY), and a vascularized periosteal flap. METHODS The carrier matrix OPLA-HY with or without rhBMP-2 was implanted in a 1-cm-long femoral defect and secured with a plate and screws. In some groups, a vascularized periosteal flap was harvested from the medial surface of the tibia. In group 1, the femoral defects in the animals were filled with the OPLA-HY matrix alone; in group 2, the OPLA-HY matrix was covered by the vascularized periosteal flap; in group 3, 20 mug of rhBMP-2 was added to the OPLA-HY matrix; and in group 4, the femoral defect containing the OPLA-HY matrix and 20 mug of rhBMP-2 was wrapped circumferentially by the vascularized periosteal flap. The presence and density of new bone formation in the femoral defect were evaluated radiographically, histologically, and with histomorphometry at four and eight weeks postoperatively. RESULTS Groups 1 and 2, which were not treated with rhBMP-2, showed no radiographic or histologic evidence of mature bone formation at four or eight weeks. Both groups 3 and 4, which were treated with rhBMP-2, demonstrated excellent bone formation. However, with the periosteal flap, group 4 demonstrated more bone formation on histomorphometric analysis at eight weeks (43.1%) than did group 3 (28.3%) (p < 0.01). Additionally, heterotopic bone formed outside the boundaries of the defect in eight of the fifteen animals in group 3, which had no periosteal flap. CONCLUSIONS Bone-tissue engineering with use of the OPLA-HY matrix and rhBMP-2 produced good bone formation in the rat femoral defect model. However, the addition of a vascularized periosteal flap significantly increased bone formation within the boundaries of the defect and prevented heterotopic ossification.

Effects of local continuous release of brain derived neurotrophic factor (BDNF) on peripheral nerve regeneration in a rat model.

The purpose of this study was to evaluate the effect of continuously released BDNF on peripheral nerve regeneration in a rat model. Initial in vitro evaluation of calcium alginate prolonged-release-capsules (PRC) proved a consistent release of BDNF for a minimum of 8 weeks. In vivo, a worst case scenario was created by surgical removal of a 20-mm section of the sciatic nerve of the rat. Twenty-four autologous fascia tubes were filled with calcium alginate spheres and sutured to the epineurium of both nerve ends. The animals were divided into 3 groups. In group 1, the fascial tube contained plain calcium alginate spheres. In groups 2 and 3, the fascial tube contained calcium alginate spheres with BDNF alone or BDNF stabilized with bovine serum albumin, respectively. The autocannibalization of the operated extremity was clinically assessed and documented in 12 additional rats. The regeneration was evaluated histologically at 4 weeks and 10 weeks in a blinded manner. The length of nerve fibers and the numbers of axons formed in the tube was measured. Over a 10-week period, axons have grown significantly faster in groups 2 and 3 with continuously released BDNF compared to the control. The rats treated with BDNF (groups 2 and 3) demonstrated significantly less autocannibalization than the control group (group 1). These results suggest that BDNF may not only stimulate faster peripheral nerve regeneration provided there is an ideal, biodegradable continuous delivery system but that it significantly reduces the neuropathic pain in the rat model.

Prefabrication of bone by use of a vascularized periosteal flap and bone morphogenetic protein

&NA; The purpose of this pilot study was to prefabricate a vascularized bone graft by using a vascularized periosteal flap containing osteoprogenitor cells, a structural matrix, and recombinant human bone morphogenetic protein‐2 (rhBMP‐2). In a rat model, a periosteal flap vascularized by the saphenous artery and vein was dissected off the medial surface of the tibia. This flap consisted of three layers—periosteum, muscle, and fascia—and was tubed on itself to form a watertight chamber that was then transferred on its vascular pedicle to the groin. A total of 78 vascularized periosteal chambers were constructed in 39 animals and divided into 10 groups. In group 1, the periosteal chamber was left empty. Groups 2, 3, and 4 consisted of the periosteal flap and rhBMP‐2, but in group 3, the proximal vascular pedicle was ligated, and in group 4, the flap was harvested without the periosteal layer and turned inside out. Groups 5 through 10 consisted of the vascularized periosteal flap containing several different structural matrices (calcium alginate spheres, polylactic acid, or demineralized bone matrix) with or without rhBMP‐2. Animals were killed at 2, 4, or 8 weeks in each group. The presence and density of any new bone formation was evaluated both radiologically and histologically. Significant bone formation was seen only in those periosteal flaps containing rhBMP‐2 and either the calcium alginate or polylactic acid matrix. New bone formation increased both radiologically and histologically from 2 weeks to 8 weeks only in the periosteal flaps containing the polylactic acid matrix and rhBMP‐2. This preliminary study therefore suggests that four factors—blood supply, osteoprogenitor cells in the periosteal layer, a biodegradable matrix, and rhBMP‐2—are required for optimal prefabrication of a vascularized bone graft.

A single localized dose of enzyme-responsive hydrogel improves long-term survival of a vascularized composite allograft

Tacrolimus-encapsulated hydrogels improve long-term survival of a vascularized composite allograft. A Leg Up for Transplant A one-shot delivery can enhance transplant survival in rats. Gajanayake et al. report that tacrolimus-encapsulated hydrogels improve long-term survival of a vascularized composite allograft (VCA). VCA is a promising alternative to reconstructive surgery or prosthesis use. However, transplant recipients must undergo systemic long-term immunosuppression, which increases their susceptibility to infection, kidney disease, and certain cancers. The authors encapsulated the immunosuppressive tacrolimus in a hydrogel composed of a material FDA classified as generally recognized as safe that was degraded by inflammatory enzymes. The tacrolimus-laden hydrogel increased graft survival time with one injection in a rat hindlimb transplant model. If reproduced in people, this delivery method could increase patient compliance and potentially decrease toxicity in transplant recipients. Currently, systemic immunosuppression is used in vascularized composite allotransplantation (VCA). This treatment has considerable side effects and reduces the quality of life of VCA recipients. We loaded the immunosuppressive drug tacrolimus into a self-assembled hydrogel, which releases the drug in response to proteolytic enzymes that are overexpressed during inflammation. A one-time local injection of the tacrolimus-laden hydrogel significantly prolonged graft survival in a Brown Norway–to–Lewis rat hindlimb transplantation model, leading to a median graft survival of >100 days compared to 33.5 days in tacrolimus only–treated recipients. Control groups with no treatment or hydrogel only showed a graft survival of 11 days. Histopathological evaluation, including anti-graft antibodies and complement C3, revealed significantly reduced immune responses in the tacrolimus-hydrogel group compared with tacrolimus only. In conclusion, a single-dose local injection of an enzyme-responsive tacrolimus-hydrogel is capable of preventing VCA rejection for >100 days in a rat model and may offer a new approach for immunosuppression in VCA.

Reconstruction of composite through-and-through mandibular defects with a double-skin paddle fibular osteocutaneous flap.

Microsurgical reconstruction of composite through-and-through defects of the oral cavity involving mucosa, bone, and external skin has often required two free flaps or double-skin paddle scapular or radial forearm flaps for successful functional and aesthetic outcomes. A safe, reliable technique using a double-skin paddle fibular osteocutaneous flap to restore the intraoral lining, mandibular bone, and external skin is described. A large elliptical or rectangular skin paddle is designed 90 degrees to the longitudinal axis of the fibula, over the junction of the middle and distal thirds of the lower leg, based only on the posterolateral septocutaneous perforators. This skin flap can be draped anteriorly and posteriorly over the fibular bone to reconstruct both the intraoral defect and the external skin defect. The area between the two skin islands of the intraoral flap and the external flap is deepithelialized and left as a dermal bridge between the two skin islands, as opposed to the creation of two separate vertical skin paddles, each based on a septocutaneous perforator. The transverse dimension of the flap can be as great as 14 cm, extending to within 1 to 2 cm of the tibial crest anteriorly and as far as the midline posteriorly, and with a length of up to 26 cm, this flap should be more than sufficient for reconstruction of most through-and-through defects. This technique has allowed the successful reconstruction of large composite defects, with missing intraoral lining, mandibular bone, and external skin, for 16 patients, with 100 percent survival of both skin islands in all cases and without the development of any orocutaneous fistulae.

IFSSH Flexor Tendon Committee report 2014: from the IFSSH Flexor Tendon Committee (Chairman: Jin Bo Tang).

Hand surgeons continue to search for the best surgical flexor tendon repair and treatment of the tendon sheaths and pulleys, and they are attempting to establish postoperative regimens that fit diverse clinical needs. It is the purpose of this report to present the current views, methods, and suggestions of six senior hand surgeons from six different countries — all experienced in tendon repair and reconstruction. Although certainly there is common ground, the report presents provocative views and approaches. The report reflects an update in the views of the committee. We hope that it is helpful to surgeons and therapists in treating flexor tendon injuries.

Preservation of Amputated Extremities by Extracorporeal Blood Perfusion; a Feasibility Study in a Porcine Model

BACKGROUND Successful extremity transplantations and replantations have to be performed within 6 h of amputation to avoid irreversible tissue loss. This study investigates ex vivo the technical feasibility and the limb preservation potential of extracorporeal whole blood perfusion in a porcine model. METHODS Forelimbs of eight large white pigs were divided into paired groups: I perfusion group, II contralateral cold ischemia controls. In group I axillary arteries and veins were cannulated and perfusion with anticoagulated autologous blood was performed for 12 h; O(2), CO(2), Hb, lactate, potassium, pH, and muscle contractility were monitored. Tissue biopsies were examined by histology and immunofluorescence. Group II was stored at 4°C. RESULTS Continuous limb perfusion could be performed in all extremities of group I for 12 h. pH was maintained normal and potassium controlled with insulin and glucose. Lactate levels increased initially during perfusion due to the lack of a metabolizing liver. Muscle stimulation was possible throughout the entire perfusion, whereas a complete loss of response was noted in cold ischemia controls. Minor tissue damage was observed histologically and by immunofluorescence in group I, whereas the samples of group II were apparently preserved with the exception of a loss of endothelial heparan sulfate. CONCLUSIONS The tissue preserving potential and the feasibility of extremity perfusion using common extracorporeal blood circulation techniques was demonstrated in this ex vivo study. The results encourage further investigations in prolonged perfusion followed by limb replantation. This approach harbors promising clinical potential for extremity preservation in extremity transplantation and replantation.

Sonographic Follow-Up of Patients With Carpal Tunnel Syndrome Undergoing Surgical or Nonsurgical Treatment: Prospective Cohort Study

PURPOSE To compare changes in the largest cross-sectional area (CSA) of the median nerve in wrists undergoing surgical decompression with changes in wrists undergoing non-surgical treatment of carpal tunnel syndrome (CTS). METHODS This study was a prospective cohort study in 55 consecutive patients with 78 wrists with established CTS, including 60 wrists treated with surgical decompression and 18 wrists with non-surgical treatment. A sonographic examination was scheduled before and 4 months after initiation of treatment. We compared changes in CSA of the median nerve between wrists with surgical treatment and wrists with non-surgical treatment using linear regression models. RESULTS Decreases in CSA of the median nerve were more pronounced in wrists with CTS release than in wrists undergoing nonsurgical treatment (difference in means, 1.0 mm(2); 95% confidence interval, 0.3-1.8 mm(2)). Results were robust to the adjustment for age, gender, and neurological severity at baseline. Among wrists with CTS release, those with postoperative CSA of 10 mm(2) or less tended to have better clinical outcomes than those with postoperative CSA of greater than 10 mm(2) (p=.055). Postoperative sonographic workup in the 3 patients with unfavorable outcome or recurrence identified likely causes for treatment failure in 2 patients. CONCLUSIONS In this observational study, surgical decompression was associated with a greater decrease in median nerve CSA than was nonsurgical treatment. Smaller postoperative CSAs may be associated with better clinical outcomes. Additional randomized trials are necessary to determine the optimal treatment strategy in different subgroups of patients with CTS. TYPE OF STUDY/LEVEL OF EVIDENCE Therapeutic III.

Fate of failed Meuli total wrist arthroplasty.

Sixteen Meuli wrist arthroplasties in 13 patients suffering mainly from rheumatoid arthritis were revised for failure. Causes for failure were mechanical problems with the implant in three wrists, soft tissue problems in two wrists and a combination of mechanical failure and soft tissue problems in 11 wrists. Management included 11 revision arthroplasties in ten wrists, four arthrodeses and two primary soft tissue reconstructions. Twenty-six additional soft tissue procedures were required in association with the revision arthroplasties or arthrodeses. Five of the 11 revision arthroplasties had to be converted to arthrodeses after an average of 5 (range 3–8) years. After removal of a failed wrist implant union of the salvage arthrodesis was diffcult to achieve in two of the nine instances. This series demonstrates that revision arthroplasty may be a useful alternative to arthrodesis for the salvage of primary wrist arthroplasties in rheumatoid patients. However, complications and reoperations may occur after both revision arthroplasty and arthrodesis.

Inter- and intraobserver reliability of predefined diagnostic levels in high-resolution sonography of the carpal tunnel syndrome - a validation study on healthy volunteers

PURPOSE High-resolution ultrasound is becoming increasingly important in the diagnosis of carpal tunnel syndrome (CTS). Most studies define cut-off values of the cross-sectional area (CSA) of the median nerve in different locations. The individual range of nerve swelling, the size of the nerve, and its CSA are not addressed. The aim of the study is to define the intra- and interobserver reliability of diagnostic ultrasound using two different cross-sectional areas of the median nerve at the carpal tunnel in predefined locations. MATERIALS AND METHODS Two observers using high-resolution ultrasound examined 50 wrists of healthy volunteers independently. The CSA of the median nerve was measured at the entrance of the carpal tunnel and 2 cm proximal to the palmar wrist crease. The height and width of the carpal tunnel were determined using anatomical landmarks. The intra- and interobserver reliability was determined using Cronbachs alpha. RESULTS Depending on the observer, the mean width of the carpal tunnel ranged from 3.37 to 3.43 cm with the height ranging from 1.18 and 1.19 cm. The CSA of the nerve was measured with values of 8.43 and 9.05 mm (2) on the pisiform level and 9.37 and 9.68 mm (2) on the proximal level. Cronbachs alpha ranged from 0.754 to 0.940 for the interobserver reliability and from 0.924 to 0.996 for the intraobserver reliability. CONCLUSION To use high-resolution ultrasound for the diagnosis of carpal tunnel syndrome, the reproducibility of this method has to be evaluated. Our study confirms examiner-independent reproducibility of two predefined diagnostic cross-sectional areas resulting in good alpha values.