Materials and manufacturing perspectives in engineering heart valves: a review.

Valvular heart diseases (VHD) are a major health burden, affecting millions of people worldwide. The treatments for such diseases rely on medicine, valve repair, and artificial heart valves including mechanical and bioprosthetic valves. Yet, there are countless reports on possible alternatives noting long-term stability and biocompatibility issues and highlighting the need for fabrication of more durable and effective replacements. This review discusses the current and potential materials that can be used for developing such valves along with existing and developing fabrication methods. With this perspective, we quantitatively compare mechanical properties of various materials that are currently used or proposed for heart valves along with their fabrication processes to identify challenges we face in creating new materials and manufacturing techniques to better mimick â€‹the performance of native heart valves.

Technique for heterotopic pig heart xenotransplantation in primates.

The primate is a commonly utilized model for the human immune response after heart transplantation. This report describes our experience with heterotopic abdominal transplantation of porcine hearts into primate recipients. Abdominal graft placement was surprisingly well tolerated, and we found this approach to be particularly useful in the setting of significant donor-recipient size mismatch. Continuous monitoring with an implantable monitoring system facilitated assessment of graft viability in awake recipients; progressive graft bradycardia and decreasing QRS amplitude were predictive of ensuing graft failure.

Vascularized auricular perichondrium in airway reconstruction: the effects of stenting with and without a mucosal graft.

This study quantitatively examines the effects of laryngotracheal stenting with and without mucosal grafting on chondrogenesis in a rabbit model. Vascularized auricular perichondrium was transferred to a cricothyroid membrane (CTM) defect in three groups of New Zealand white rabbits: group A, CTM defect alone; group B, CTM defect with endotracheal tube stent; and group C, CTM defect with a buccal mucosa graft (BMG) interposed between the stent and perichondrium. The rabbits were sacrificed at 7 weeks for histologic examination and determination of cartilage thickness by digitometry. Chondrogenesis was not significantly affected by stenting (n = 11; 0.719 mm +/- 0.203 mm) or by BMG (n = 12; 0.775 mm +/- 0.203 mm) as compared with controls (n = 14; 0.695 mm +/- 0.216 mm) (P value = not significant). Laryngotracheal stenting and BMG do not adversely influence chondrogenesis in airway reconstruction with vascularized perichondrium in the rabbit model. The application of these principles in human airway reconstruction is discussed.

Lengthening the short nose.

Correction of the aesthetically short nose is one of the most challenging problems in facial plastic surgery. We discuss several techniques aimed at the correction of this problem and propose an algorithm based on the desired effect of the lengthening procedure on tip rotation. Five principal techniques for nasal lengthening are discussed, with figures and cases to illustrate the concepts: (1) the flying buttress graft, which is made up of a single or paired spreader grafts secured to a columellar strut; (2) caudal septal grafts and (3) tip grafts of various shapes; (4) radix grafts placed to elevate the nasion; and (5) interposition grafts placed between the upper and lower lateral cartilages. When the tip is overrotated, small to moderate gains in nasal length may be achieved by a triangular-shaped caudal septal graft or a shield graft that is backed by wedge grafts near the tip. More substantial lengthening and derotation can be achieved by the flying buttress technique or by interposition cartilage or composite grafting between the upper and lower lateral cartilages. With a nasal tip that is adequately rotated or underrotated, nasal lengthening can be achieved by a rectangular-shaped caudal septal graft or by a full-length shield graft. An onlay graft to augment the radix and elevate the nasion to a higher point on the dorsum can be used alone or in combination with a tip or septal graft.

Effect of intraoperative ischemia on chondrogenesis by vascularized auricular perichondrium grafted in the airway.

Vascularized perichondrium and periosteum are potentially ideal grafts for airway reconstruction. We quantitatively evaluated the effect of a 2-hour interruption of blood supply on subsequent growth of cartilage from vascularized auricular perichondrium grafted in the rabbit airway. Two pedicled auricular perichondrocutaneous flaps were elevated and used to repair two small anterior airway defects in each animal (n = 17). One of the two flaps was randomly clamped for a 2-hour period during the operation, with the other flap serving as a paired control. We found no significant difference in chondrogenesis between the two groups. Our findings support the use of perichondrium and periosteum as free revascularized grafts for airway reconstruction.

Reconstruction of the rabbit trachea with vascularized auricular perichondrium.

Success in laryngotracheal reconstruction has been limited, in part, by the lack of an ideal grafting material. Perichondrium is thin, pliable, and highly vascularized and has the ability to generate new cartilage providing rigid support. These qualities make vascularized perichondrium potentially the ideal grafting material for circumferential airway stenosis. A pedicled vascularized flap of auricular perichondrium was used in a rabbit model (n = 39) to reconstruct a near-circumferential tracheal defect without a tracheostomy. A stent was used to support the reconstructed airway for 6 weeks, after which time it was removed by direct laryngoscopy. Animals were observed for an additional 6 weeks prior to sacrifice. Qualitative and quantitative histologic analysis of neochondrogenesis is reported. Vascularized perichondrium and periosteum show promise as potential grafts for reconstruction of circumferential tracheal defects.

The extended Abbe flap in the reconstruction of complex midfacial defects.

The Abbe flap is most commonly used to repair full-thickness defects of the lip that do not involve the commissure. This well-perfused axial flap is based on the labial branches of the facial artery. The inferior labial vessels have been shown to support a cutaneous territory, including the entire lower lip, chin, and submental skin. Defects extending beyond the confines of the upper lip may be reconstructed with an extended lip switch flap that is based on the inferior labial artery. This "extended" Abbe flap allows functional and cosmetically acceptable repair of the upper lip, medial cheek, columella, and nasal sill. Case presentations illustrate the technique and outcome.

Effect of nucleotide on the binding of peptides to 70-kDa heat shock protein.

In previous work we found that bovine brain hsp70 has a single binding site for nucleotide, and that, with ATP at this site, the rates of association and dissociation of clathrin from hsp70 are fast, whereas with ADP at this site, these rates are unmeasurably slow. In the present study we show, first, that peptide C, cytochrome c peptide, and RNase S peptide bind competitively with clathrin, suggesting that they bind to the same site on hsp70, although RNase S peptide binds an order of magnitude more weakly than peptide C and cytochrome c peptide. Second, we show that, with ADP bound to hsp70, as occurs with clathrin, the rate constant for dissociation of peptide markedly decreases compared to the rate constant observed in ATP. In contrast, ADP only slightly decreases the rate of association of peptide. Based on these data we propose a model in which substrates of hsp70 bind to and dissociate from the ATP form of the enzyme, while, following ATP hydrolysis, they are locked onto the ATP form of the enzyme, unable to dissociate until ADP is released and ATP rebinds.

Role of unsaturated derivatives of spermidine as substrates for spermine synthase and in supporting growth of SV-3T3 cells.

Synthetic unsaturated analogues of the natural polyamine were examined as possible substrates for spermine synthase and as replacements for spermidine in supporting the growth of SV-3T3 cells. It was found that N-(3-aminopropyl)-1,4-diamino-cis-but-2-ene [the cis isomer of the alkene analogue of spermidine] was a good substrate for spermine synthase, but that the trans isomer [N-(3-aminopropyl)-1,4-diamino-trans-but-2-ene] and the alkene analogue [N-(3-aminopropyl)-1,4-diaminobut-2-yne] were not substrates. These results provide the first demonstration of stereospecificity in the spermine synthase reaction. All three of the unsaturated spermidine analogues described above and the cis-alkene analogue of spermine [N1N4-bis-(3-aminopropyl)-1,4-diamino-cis-but-2-ene] were able to support the growth of SV-3T3 cells that were prevented from the endogenous synthesis of spermidine by treatment with alpha-difluoromethylornithine. Since N-(3-aminopropyl)-1,4-diamino-trans-but-2-ene] and N-(3-aminopropyl)-1,4-diaminobut-2-yne were not converted into a spermine derivative, it is apparent that this conversion is not needed for the stimulation of growth. However, since N1N4-bis-(3-aminopropyl)-1,4-diamino-cis-but-2-ene was also able to support growth and was not degraded to the spermidine derivative, it appears that either polyamine can be effective in this respect. All of the unsaturated analogues tested accumulated in the SV-3T3 cells to a much greater extent than spermidine itself. This indicates that these compounds are substrates for the polyamine transport system, but that they are less effective than the natural polyamines in the feedback regulation of this system.

Adenoid cystic carcinoma of the paranasal sinuses.

Adenoid cystic carcinoma of the paranasal sinuses is a rare neoplasm whose propensity for perineural spread frequently results in positive surgical margins at the skull base. Radiation therapy (RT) may be used to treat unresectable tumors or as an adjuvant for positive surgical margins after attempted resection. A retrospective review of the experience at the University of Michigan Medical Center was undertaken to study the factors influencing survival and to compare the efficacy of RT alone versus as an adjuvant treatment to surgical resection. All patients selected for review (n = 17) had a histologically confirmed diagnosis of adenoid cystic carcinoma arising from the paranasal sinuses with an average follow-up of 6 years. The choice of treatment modality was based upon the resectability of the tumor by clinical and radiologic parameters. This was therefore not a randomized study and there was a clear bias against the radiation only group, which contained the more advanced and locally aggressive tumors. The 6-year survival for the combined surgery + RT group was 73% compared with 50% for the radiation only group (p = NS). The overall local recurrence rate was 76% and the rate of distant metastases was 18%. Of the 10 patients who underwent surgical resection eight (80%) had positive surgical margins at the skull base.

Hearts from transgenic pigs constructed with CD59/DAF genomic clones demonstrate improved survival in primates.

We have previously created transgenic pigs bearing the human complement regulatory proteins CD59 and decay-accelerating factor (DAF) by either the intercellular transfer or the cDNA transgenic method. To achieve more physiologic protein expression, we constructed a new line of transgenic pigs with CD59 and DAF human genomic clones. We transplanted these CD59/DAF transgenic pig hearts into baboons immunosuppressed with cyclosporine, methylprednisone or leflunomide/mofetil mycophenolate. The four wild-type hearts survived for 20-80 min, whereas the four CD59/DAF hearts functioned for 85-130 h. Immunohistochemical staining showed levels of CD59 and DAF protein expression similar to that in human hearts. Wild-type and transgenic hearts demonstrate a similar level of IgM deposition, although transgenic hearts suffered less hyperacute rejection and thus less membrane attack complex deposition. The histology of the transgenic grafts after explant was consistent with acute vascular rejection, with a high level of IgG deposit compared with wild-type control. We conclude that this new line of CD59/DAF transgenic pigs express high levels of the transgene products, which conferred longer survival because of better protection from hyperacute rejection. Similar to previous transgenic pigs, however, these animals suffered from delayed xenograft rejection.