Physiological function and transplantation of scaffold-free and vascularized human cardiac muscle tissue.

Success of human myocardial tissue engineering for cardiac repair has been limited by adverse effects of scaffold materials, necrosis at the tissue core, and poor survival after transplantation due to ischemic injury. Here, we report the development of scaffold-free prevascularized human heart tissue that survives in vivo transplantation and integrates with the host coronary circulation. Human embryonic stem cells (hESCs) were differentiated to cardiomyocytes by using activin A and BMP-4 and then placed into suspension on a rotating orbital shaker to create human cardiac tissue patches. Optimization of patch culture medium significantly increased cardiomyocyte viability in patch centers. These patches, composed only of enriched cardiomyocytes, did not survive to form significant grafts after implantation in vivo. To test the hypothesis that ischemic injury after transplantation would be attenuated by accelerated angiogenesis, we created "second-generation," prevascularized, and entirely human patches from cardiomyocytes, endothelial cells (both human umbilical vein and hESC-derived endothelial cells), and fibroblasts. Functionally, vascularized patches actively contracted, could be electrically paced, and exhibited passive mechanics more similar to myocardium than patches comprising only cardiomyocytes. Implantation of these patches resulted in 10-fold larger cell grafts compared with patches composed only of cardiomyocytes. Moreover, the preformed human microvessels anastomosed with the rat host coronary circulation and delivered blood to the grafts. Thus, inclusion of vascular and stromal elements enhanced the in vitro performance of engineered human myocardium and markedly improved viability after transplantation. These studies demonstrate the importance of including vascular and stromal elements when designing human tissues for regenerative therapies.

The effects of force inhibition by sodium vanadate on cross-bridge binding, force redevelopment, and Ca2+ activation in cardiac muscle.

Strongly bound, force-generating myosin cross-bridges play an important role as allosteric activators of cardiac thin filaments. Sodium vanadate (Vi) is a phosphate analog that inhibits force by preventing cross-bridge transition into force-producing states. This study characterizes the mechanical state of cross-bridges with bound Vi as a tool to examine the contribution of cross-bridges to cardiac contractile activation. The K(i) of force inhibition by Vi was approximately 40 microM. Sinusoidal stiffness was inhibited with Vi, although to a lesser extent than force. We used chord stiffness measurements to monitor Vi-induced changes in cross-bridge attachment/detachment kinetics at saturating [Ca(2+)]. Vi decreased chord stiffness at the fastest rates of stretch, whereas at slow rates chord stiffness actually increased. This suggests a shift in cross-bridge population toward low force states with very slow attachment/detachment kinetics. Low angle x-ray diffraction measurements indicate that with Vi cross-bridge mass shifted away from thin filaments, implying decreased cross-bridge/thin filament interaction. The combined x-ray and mechanical data suggest at least two cross-bridge populations with Vi; one characteristic of normal cycling cross-bridges, and a population of weak-binding cross-bridges with bound Vi and slow attachment/detachment kinetics. The Ca(2+) sensitivity of force (pCa(50)) and force redevelopment kinetics (k(TR)) were measured to study the effects of Vi on contractile activation. When maximal force was inhibited by 40% with Vi pCa(50) decreased, but greater force inhibition at higher [Vi] did not further alter pCa(50). In contrast, the Ca(2+) sensitivity of k(TR) was unaffected by Vi. Interestingly, when force was inhibited by Vi k(TR) increased at submaximal levels of Ca(2+)-activated force. Additionally, k(TR) is faster at saturating Ca(2+) at [Vi] that inhibit force by > approximately 70%. The effects of Vi on k(TR) imply that k(TR) is determined not only by the intrinsic properties of the cross-bridge cycle, but also by cross-bridge contribution to thin filament activation.

Development and evaluation of a novel decellularized vascular xenograft.

Although autogenous saphenous vein remains the standard for coronary and infrapopliteal bypass, many patients do not have a suitable vein. Attempts at developing a small-caliber vascular graft have failed largely due to occlusion, neointimal hyperplasia, or aneurismal degradation. We have designed and characterized a novel small-caliber vascular xenograft that may overcome these failure modes. To reduce immune reactions, porcine common carotid arteries were decellularized by enzymatic and detergent treatments. Histology and electron microscopic examination showed complete removal of cellular components while the extracellular matrix structure remained intact. To reduce thrombogeneity, decellularized vascular grafts were covalently linked with heparin. The efficiency of heparin linkage was demonstrated with toluidine blue staining and the antithrombogeneity of the heparin-treated grafts was demonstrated with a clot time test. Mechanical testing of the graft was performed. Decellularized-heparin-treated grafts were similar in compliance to fresh vessels and burst testing showed grafts to withstand pressures exceeding 10 times physiologic blood pressure. There was no difference in suture retention strength between fresh vessels and decellularized-heparin-treated grafts. Decellularized, heparinized grafts were implanted in dogs as carotid artery bypass grafts and showed smooth muscle cells densely populating the wall, and endothelial cells lining the lumen by two months. This study provides a new strategy to develop a small-caliber vascular graft with excellent mechanical properties, antithrombogeneity, and tissue compatibility.

Fractures of the maxilla.

A basic understanding of midface fractures is essential for those involved in the initial evaluation, emergency and general management, diagnosis, specialty consultation, and maxillofacial surgery of patients with fractures of the maxilla. To achieve the goal of restoring proper form and function to the upper jaw and face, one must be able to recognize, diagnose, and treat maxillary fractures. This requires knowledge of the anatomy and physiology of the midface, as well as modalities of evaluation and treatment. Each of these topics are summarized in this paper.

Allergic fungal sinusitis.

Allergic fungal sinusitis (AFS) is a recently described entity that has been frequently misdiagnosed in the past. AFS is now felt to be the most common cause of fungal sinusitis. There is now a sufficient experience to make the diagnosis and the causative organisms have been elucidated. However, controversy continues to surround the pathophysiology and treatment of this challenging disease.

Penetrating injuries of the face.

In dealing with gunshot wounds to the face, the emergency department physician should have a basic knowledge of ballistics. Securing an airway (either intubation or surgical airway) should be the top priority. The location of the wound dictates which patient should be intubated. Plain x-ray films of the face and skull, as well as CT scan in certain situations, allow determination of the extent of damages to the skeleton as well as intracranial injuries. Clinical symptoms suggesting an underlying vascular injury require an angiogram. After thorough debridement of the wounds, fractures are treated either with open-reduction and internal fixation or closed-reduction and intermaxillary fixation.

Cementifying fibroma: resection of recurrent mandibular lesion with microsurgical preservation of inferior alveolar nerve and immediate reconstruction.

Cementifying fibroma is a benign fibro-osseous lesion that may occur in either the mandible or the maxilla, with a predilection for the mandible. In the patient described, a recurrent mandibular cementifying fibroma was successfully resected, with microsurgical preservation of the inferior alveolar nerve and immediate reconstruction via an autogenous iliac bone graft.

Surgical management of the temporomandibular joint in resection of regional tumors.

The temporomandibular joint (TMJ) may require surgical violation or resection when involved in primary malignant or benign tumors of bone, regional tumors of the oral cavity adjacent to the mandible or with mandibular erosion, or in soft tissue tumors around the joint. The TMJ may require total resection with or without reconstruction, subtotal resection with preservation of the glenoid fossa and meniscus, resection of the capsule with dermal graft reconstruction, condylar resection with reconstruction, or subcondylar resection with mandibular reconstruction. TMJ anatomy is important in using joint structures as margins in resection of tumors, in preservation of uninvolved structures to obtain maximum joint function after surgery, and in reconstruction of ablated structures to reestablish joint function. Surgical cases are presented to illustrate surgical management and rehabilitation of the TMJ.

Zygomatic fractures: reduction with the T-bar screw.

The prominent zygomatic bone is one of the most commonly fractured. Fracture with displacement of the bone results in a cosmetic and functional deformity. The fractured zygomatic bone is usually dislocated in an inferomedial and posterior direction, which results in a cosmetic deformity with loss of ipsilateral malar prominence, possible depression of the zygomatic arch, asymmetry of the bony orbital circumference, and possible enophthalmos. Fracture of the zygomatic bone may result in ocular, maxillary antral, and mandibular dysfunction; diplopia, restricted extraocular muscle movement, or intraocular injuries; infection or obstruction of the maxillary antrum; and restricted mandibular function and malocclusion. Various surgical methods have been used to reduce the displaced fractured zygomatic bone. Our preferred method for reduction is the T-bar (Carroll-Girard) screw. This clinical study reviews 30 cases of zygomatic complex fractures, outlines the surgical technique used, illustrates the proper use of the T-bar screw with anatomic schematics and clinical cases, and presents illustrative case summaries.

Cysts of the mandible and maxilla.

Mandibular and maxillary cysts originate from elements of the teeth (odontogenic), or from epithelial remnants trapped in fusion lines during development (nonodontogenic). Both types can be clinically asymptomatic and must be treated surgically. The specific diagnosis of a jaw cyst and its recurrence depends upon the anatomical location, the radiographic appearance, and the pathological diagnosis.

Comprehensive surgical management of mandibular fractures.

Mandibular fractures are common facial injuries. Classifications are combined and correlated with specific treatment modalities. Combined classification of fractures indicates the difficulty of treatment required. Many surgical techniques have been used and accepted as proper methods for reduction and fixation of mandibular fractures. Most studies advocate one technique as superior to others. The range of procedures now available include observation, closed reduction with maxillomandibular fixation, transoral reduction, intraosseous wire fixation, miniplate rigid osseous fixation, compression rigid osseous fixation, and external skeletal fixation. Our evaluation of the specific advantages of each modality indicates that selection of a specific procedure is individualized according to combined classification of the mandibular fracture, the surgical procedure's advantages and disadvantages, the patient's desires, and the surgeon's ability and clinical judgment. Case presentations demonstrate the principles involved in comprehensive surgical management of mandibular fractures. The techniques advocated produce anatomic reduction and restoration of physiologic function and aesthetics, with rare complications.

Giant fibrous dysplasia of the mandible: surgical management.

Giant fibrous dysplasia of the mandible (GFDM) represents a far advanced lesion which may be monostotic, polyostotic, a component of craniofacial fibrous dysplasia, a component of Albright's syndrome, or associated with other endocrinopathies. The current philosophy is to consider fibrous dysplasia of the mandible (FDM) as one of a group of lesions classified as fibro-osseous lesions of the jaws. The natural course and manifestations in the mandible result in GFDM if they are unabated by curative therapy or if stabilization or regression does not occur. A rational therapeutic approach depends upon the extent of the disease at the time of diagnosis. The earlier in the disease process that the diagnosis is made, the more likely that a curative surgical procedure may be undertaken. Complete resection of the diseased mandible should be performed when feasible. A lesser surgical procedure has no curative potential and is performed only as a palliative, cosmetic delaying procedure.

Extended modified postauricular incision of the temporomandibular joint.

The traditional postauricular approach to the temporomandibular joint has excellent cosmetic results since the entire incision is concealed in the postauricular flexure. Excellent posterior joint exposure, good lateral joint exposure, and fair anterior joint exposure are obtained. The risk of injury to the facial nerve is decreased. An extended modification of the postauricular incision was developed to overcome some of the disadvantages of the postauricular incision while maintaining its advantages. The incision begins inferiorly in a curvilinear manner, over the mastoid tip and progresses superiorly 3 mm posterior to the postauricular flexure. As it ascends superiorly above the level of the external auditory canal, it progresses posteriorly from the flexure. It then progresses superiorly in a curvilinear fashion in the temporal area slightly superior to the customary superior aspect of the preauricular incision. The dissection is carried to and through the temporalis fascia and periosteum, over the root of the zygomatic arch, and anteriorly after crosscut of the external auditory canal to the parotideomasseteric fascia. Dissection anteriorly deep to these fused structures allows a single flap to the skin. With this anterior dissection, the temporal and zygomatic branches of the facial nerve are protected and contained within the skin-fascia flap. The capsule is thus exposed and further dissection into the joint is described. A representative case presentation demonstrates the extended modified postauricular incision.

Partial palatomaxillary core ostectomy with multiple flap reconstruction.

Epidermoid carcinoma of the hard palate has most commonly been treated by surgical procedures such as total maxillectomy, hemimaxillectomy, palatectomy, intraoral maxillectomy, and local resection, which leaves the patient with problems of velopharyngeal incompetence, oral-nasal or oral-antral fistula, or an inability to wear a denture. This article describes a surgical procedure that uses a partial core palatomaxillary ostectomy for ablation and multiple buccal and palatal flaps for primary closure, thereby avoiding these postoperative problems.

Surgery of the temporomandibular joint. I. Surgical anatomy and surgical incisions.

Surgical anatomy is highly specific and correlates well with the surgical approaches to the temporomandibular joint (TMJ). The preauricular, endaural, and postauricular incisions are used for conventional surgery and microsurgery of the TMJ. Indications for the selection of the desired incision are given. The surgical technique of each incision is described in detail. Elevation of a continuous superoinferior flap of the temporalis fascia, the periosteum over the zygomatic arch, and the paratideomasseteric fascia lifts up and protects the branches of the facial nerve. Elevation in this fascia plane results in a skin-fascia flap with the branches of the facial nerve contained and protected within the tissues. This basic skin-fascia flap is developed in all three incisions--the preauricular, the endaural, and the postauricular.

Surgery of the temporomandibular joint. II. Microsurgery.

The operating microscope has revolutionized many surgical procedures. Pioneering microtechniques for exploring and reconstructing the temporomandibular joint have been modified. The preauricular, endaural, and postauricular incisions may be used for approaching the temporomandibular joint in microsurgery procedures. Determinations of pathologic conditions and observations of temporomandibular joint function-dysfunction are dramatic and rewarding. Precision surgery using microinstruments, microneedles, microdrills, bipolar cautery, and the laser allows accuracy of technique that previously was impossible. Representative case presentations illustrate patient treatment, surgical incision, microsurgical technique employed, and clinical results obtained.

Complex maxillofacial fractures: management and surgical procedures.

Complex maxillofacial fractures may be defined as combined, mixed, or unclassified. Adequate diagnostic technics must be used with the formulation of a plan for general management and sequential maxillofacial surgery. The basic principal of building from the stable mandible to the first superior stable bone must be adhered to. Exploration of all fracture sites with direct reduction and fixation is the most satisfactory technic for best cosmetic and functional results. The maxillary buccal vestibule incision in midfacial fractures provides exploration of the lateral walls of the maxilla, nasal aperture, zygomatic buttress, maxillary tuberosity and pterygoid area, maxillary antrum and roof (or orbital floor), and infraorbital rim. The extent of the injury can be determined and direct reduction and fixation obtained. Additional approaches for reduction and internal stabilization are used according to the findings. When direct wiring technics are inadequate, internal and external skeletal fixation must be used.

Microsurgical approach to the temporomandibular joint. A new horizon.

The operating microscope has revolutionized many surgical procedures. To my knowledge, this article records for the first time, pioneering microtechniques for exploring and reconstructing the temporomandibular joint. Determination of pathologic conditions and observation of temporomandibular joint function-dysfunction are dramatic and rewarding. Precision surgery using microinstruments, microneedles, microdrills, and bipolar cautery allows accuracy of technique that previously was impossible. Two representative case presentations illustrate patient treatment, microsurgical technique employed, and clinical results obtained.

Surgical management of complex maxillofacial fractures.

The surgical treatment of severe and complex maxillofacial injuries requires sophisticated modalities. Personal surgical principles of maxillofacial trauma management are delineated. Exploration of all fracture sites with direct reduction and fixation is the most satisfactory technique for best cosmetic and functional results. The maxillary buccal vestibule incision is stressed for routine use in midfacial fractures. A plea is made for utilization of this incision for exploration of the lateral wall of the maxilla, the nasal aperture, the zygomatic buttress, maxillary tuberosity and pterygoid area, the maxillary antrum and roof (or orbital floor), and the infraorbital rim. The extent of the injury can be ascertained and direct reduction and fixation obtained. Two case presentations illustrate the complex management of such injuries. Postoperative follow-up demonstrates the cosmetic results and rehabilitation of properly managed cases.