Background— Cardiac tissue engineering offers the prospect of a novel treatment for acquired or congenital heart defects. We have created vascularized pieces of beating cardiac muscle in the rat that are as thick as the adult rat right ventricle wall. Method and Results— Neonatal rat cardiomyocytes in Matrigel were implanted with an arteriovenous blood vessel loop into a 0.5-mL patented tissue-engineering chamber, located subcutaneously in the groin. Chambers were harvested 1, 4, and 10 weeks after insertion. At 4 and 10 weeks, all constructs that grew in the chambers contracted spontaneously. Immunostaining for α-sarcomeric actin, troponin, and desmin showed that differentiated cardiomyocytes present in tissue at all time points formed a network of interconnected cells within a collagenous extracellular matrix. Constructs at 4 and 10 weeks were extensively vascularized. The maximum thickness of cardiac tissue generated was 1983 μm. Cardiomyocytes increased in size from 1 to 10 weeks and were positive for the proliferation markers Ki67 and PCNA. Connexin-43 stain indicated that gap junctions were present between cardiomyocytes at 4 and 10 weeks. Echocardiograms performed between 4 and 10 weeks showed that the tissue construct contracted spontaneously in vivo. In vitro organ bath experiments showed a typical cardiac muscle length-tension relationship, the ability to be paced from electrical field pulses up to 3 Hz, positive chronotropy to norepinephrine, and positive inotropy in response to calcium. Conclusion— In summary, the use of a vascularized tissue-engineering chamber allowed generation of a spontaneously beating 3-dimensional mass of cardiac tissue from neonatal rat cardiomyocytes. Further development of this vascularized model will increase the potential of cardiac tissue engineering to provide suitable replacement tissues for acquired and congenital defects.
The final judgment of whether to replant may not be determined until after microscopic inspection of vessels and nerves is complete. Once committed, it is ultimately the attention to detail that will determine function; bone shortening and rigid fixation, multiple strand flexor tendon repair, and quality, meticulous repair of the extensor mechanism to permit early movement, periosteal approximation to aid gliding, radical debridement of damaged vessels and primary skin closure.
Locally advanced cutaneous malignancy of the scalp and forehead is a disease that requires an aggressive approach to resection and reconstruction. Free flap reconstruction in these sites has been advocated because of the advantages of importing large amounts of well-vascularized tissue into a recipient site, which has often been compromised by previous surgery or radiotherapy. A consecutive series of 32 free flap reconstructions in 29 patients with cutaneous malignancy of the scalp and forehead was reviewed. The flap failure rate was 6% (two flaps) and the major complication rate was 10%. Of the surviving flaps, 97% (N = 29) were successful in reconstructing a challenging group of defects. Three patients developed local recurrence of the primary malignancy (mean follow-up, 21 months). The use of a broad repertoire of free tissue transfers in reconstruction of the scalp and forehead defects has allowed effective treatment of locally advanced malignancy of this region. Critical analysis of the results, however, indicates that microsurgical reconstruction is not without morbidity and that there are refinements in the diagnostic and operative steps of management that can maximize the functional and aesthetic results.
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