Impact of surgical innovation on tissue repair in the surgical patient.

BACKGROUND: Throughout history, surgeons have been prolific innovators, which is hardly surprising as most surgeons innovate daily, tailoring their intervention to the intrinsic uniqueness of each operation, each patient and each disease. Innovation can be defined as the application of better solutions that meet new requirements, unarticulated needs or existing market needs. In the past two decades, surgical innovation has significantly improved patient outcomes, complication rates and length of hospital stay. There is one key area that has great potential to change the face of surgical practice and which is still in its infancy: the realm of regenerative medicine and tissue engineering. METHODS: A literature review was performed using PubMed; peer-reviewed publications were screened for relevance in order to identify key surgical innovations influencing regenerative medicine, with a focus on osseous, cutaneous and soft tissue reconstruction. RESULTS: This review describes recent advances in regenerative medicine, documenting key innovations in osseous, cutaneous and soft tissue regeneration that have brought regenerative medicine to the forefront of the surgical imagination. CONCLUSION: Surgical innovation in the emerging field of regenerative medicine has the ability to make a major impact on surgery on a daily basis.

Wound healing and regenerative strategies.

Wound healing is a complex biological process that affects multiple tissue types. Wounds in the oral cavity are particularly challenging given the variety of tissue types that exist in close proximity to one another. The goal of regenerative medicine is to facilitate the rapid replacement of lost or damaged tissue with tissue that is functional, and physiologically similar to what previously existed. This review provides a general overview of wound healing and regenerative medicine, focusing specifically on how recent advances in the fields of stem cell biology, tissue engineering, and oral disease could translate into improved clinical outcomes.

Quantifying migration and polarization of murine mesenchymal stem cells on different bone substitutes by confocal laser scanning microscopy.

INTRODUCTION: Cell migration is preceded by cell polarization. The aim of the present study was to evaluate the impact of the geometry of different bone substitutes on cell morphology and chemical responses in vitro. MATERIALS AND METHODS: Cell polarization and migration were monitored temporally by using confocal laser scanning microscopy (CLSM) to follow green fluorescent protein (GFP)±mesenchymal stem cells (MSCs) on anorganic cancellous bovine bone (Bio-Oss(®)), ß-tricalcium phosphate (ß-TCP) (chronOS(®)) and highly porous calcium phosphate ceramics (Friedrich-Baur-Research-Institute for Biomaterials, Germany). Differentiation GFP±MSCs was observed using pro-angiogenic and pro-osteogenic biomarkers. RESULTS: At the third day of culture polarized vs. non-polarized cellular sub-populations were clearly established. Biomaterials that showed more than 40% of polarized cells at the 3rd day of culture, subsequently showed an enhanced cell migration compared to biomaterials, where non-polarized cells predominated (p<0.003). This trend continued untill the 7th day of culture (p<0.003). The expression of vascular endothelial growth factor was enhanced in biomaterials where cell polarization predominated at the 7th day of culture (p=0.001). CONCLUSIONS: This model opens an interesting approach to understand osteoconductivity at a cellular level. MSCs are promising in bone tissue engineering considering the strong angiogenic effect before differentiation occurs.

Bone formation and degradation of a highly porous biphasic calcium phosphate ceramic in presence of BMP-7, VEGF and mesenchymal stem cells in an ectopic mouse model.

INTRODUCTION: Angiogenesis and mesenchymal stem cells (MSCs) promote osteogenesis. The aim of the present study was to evaluate whether bone morphogenetic protein (BMP-7) promoted osteoinduction could be enhanced by combining it with vascular endothelial growth factor (VEGF) or MSCs in highly porous biphasic calcium phosphate (BCP) ceramics. MATERIALS AND METHODS: BCP ceramic blocks were implanted in an ectopic site in 24 mice (BMP-7 vs. BMP-7/VEGF; BMP-7 vs. BMP-7/MSCs and BMP-7 vs. Control; each group n=8). Specimens were analysed 12 weeks after surgery by environmental scanning electron microscopy (ESEM) and Giemsa staining. RESULTS: In all implanted scaffolds, newly formed bone was observed, even in the control site. No statistical differences in the amount of new bone were found in the presence of BMP-7 compared to BMP-7/VEGF (p=1.0) or BMP-7/MSCs (p=0.786). ESEM revealed a degradation of the scaffolds. A higher degradation was observed in areas where no bone-implant contact was present compared to areas where the ceramic was integrated in newly formed bone. CONCLUSIONS: Neither VEGF nor MSCs enhanced BMP-7 induced bone formation under the selected conditions. The present ceramic seemed to be osteoinductive and degradable, making this material suitable for bone tissue engineering.

Reduction mammoplasty improves breast conservation therapy in patients with macromastia.

BACKGROUND: Macromastia has been considered a contraindication to breast conservation therapy because of difficulties with radiation therapy. This study evaluates the feasibility of bilateral reduction mammoplasty as a component of breast conservation therapy for breast cancer patients with pendulous breasts. METHODS: Of 153 patients undergoing reduction mammoplasty at the University of Texas M. D. Anderson Cancer Center, 28 were identified as breast cancer patients with macromastia receiving breast conservation therapy. Median follow-up was 23.8 months. RESULTS: Median patient age was 55 years. Nearly all patients were described as obese. Median weight of the reduction mammoplasty specimen on the cancerous side was 766 g. One patient (4%) required completion mastectomy for inadequate margin control. Major postoperative complications occurred in 2 patients (7%). There were no major postradiation complications. Patient survey revealed a satisfaction rate of 86%. CONCLUSION: Bilateral reduction mammoplasty is a reasonable and safe option for breast cancer patients with macromastia who desire breast conservation therapy.

Advances in head and neck reconstruction.

Head and neck deformities, which can be caused by trauma, congenital defects, infections, or neoplasms, produce a stereotypical constellation of functional and aesthetic deficits, depending on the specific anatomic region. These deformities can be classified into six major anatomic categories: intraoral, mandibular, midfacial, cranial base, cutaneous, and scalp. This article presents a reliable approach to the reconstruction of these six areas that is used at the University of Texas M. D. Anderson Cancer Center. The emphasis is on an analysis of the unique functional and aesthetic problems presented by each of these specific anatomic lesions, and the reconstructive options are selected to maximize outcomes. The problems and limitations of current methods are discussed, and areas of potential development are explored.

Immunotargeting of liposomes to activated vascular endothelial cells: a strategy for site-selective delivery in the cardiovascular system.

Endothelial-selective delivery of therapeutic agents, such as drugs or genes, would provide a useful tool for modifying vascular function in various disease states. A potential molecular target for such delivery is E-selectin, an endothelial-specific cell surface molecule expressed at sites of activation in vivo and inducible in cultured human umbilical vein endothelial cells (HUVEC) by treatment with cytokines such as recombinant human interleukin 1beta (IL-1beta). Liposomes of various types (classical, sterically stabilized, cationic, pH-sensitive), each conjugated with mAb H18/7, a murine monoclonal antibody that recognizes the extracellular domain of E-selectin, bound selectively and specifically to IL-1beta-activated HUVEC at levels up to 275-fold higher than to unactivated HUVEC. E-selectin-targeted immunoliposomes appeared in acidic, perinuclear vesicles 2-4 hr after binding to the cell surface, consistent with internalization via the endosome/lysosome pathway. Activated HUVEC incubated with E-selectin-targeted immunoliposomes, loaded with the cytotoxic agent doxorubicin, exhibited significantly decreased cell survival, whereas unactivated HUVEC were unaffected by such treatment. These results demonstrate the feasibility of exploiting cell surface activation markers for the endothelial-selective delivery of biologically active agents via immunoliposomes. Application of this targeting approach in vivo may lead to novel therapeutic strategies in the treatment of cardiovascular disease.

Effect of carbon dioxide pneumoperitoneum on bacteraemia and endotoxaemia in an animal model of peritonitis.

Laparoscopy is increasingly used in conditions complicated by peritonitis. A theoretical concern is that carbon dioxide pneumoperitoneum may increase bacteraemia. This study examines the effect of carbon dioxide pneumoperitoneum on bacteraemia, endotoxaemia and physiological correlates of sepsis in an animal model of peritonitis. New Zealand white rabbits were assigned to three groups of six animals. Group 1 received an intraperitoneal inoculation of 10(9) colony-forming units of Escherichia coli followed by a 10-cm midline laparotomy. Group 2 received an identical bacterial inoculum followed by a 12-mmHg carbon dioxide pneumoperitoneum for 1 h. Group 3 received no bacteria but had a 12-mmHg carbon dioxide pneumoperitoneum for 1 h. Groups 1 and 2 had significantly higher levels of bacteraemia (P < 0.01) and endotoxaemia (P < 0.01) accompanied by significantly lower mean arterial pressures (P < 0.05) and higher heart rates (P < 0.05) compared with group 3. After 6 h groups 1 and 2 were significantly hypocarbic (P < 0.01), leucopenic (P < 0.01) and thrombocytopenic (P < 0.01). There was no difference between group 1 and group 2. A carbon dioxide pneumoperitoneum of 12 mmHg does not increase bacteraemia or endotoxaemia, nor does it adversely affect physiological or laboratory correlates of sepsis compared with laparotomy in this animal model of peritonitis.

Targeted disruption of the murine VCAM1 gene: essential role of VCAM-1 in chorioallantoic fusion and placentation.

Vascular cell adhesion molecule-1 (VCAM-1) is expressed on vascular endothelium in a variety of inflammatory conditions and mediates leukocyte recruitment from blood into tissues. In this study we report a novel role for VCAM-1 in the formation of the umbilical cord and placenta during development. The murine VCAM1 gene was disrupted by targeted homologous recombination, and a distinct phenotype was found in VCAM-1-deficient embryos. At 8.5 days of gestation, the allantois failed to fuse to the chorion, resulting in abnormal placental development and embryonic death within 1-3 days. In addition, a role for VCAM-1 in early placental formation after chorioallantoic fusion was observed. In a minority of VCAM-1-deficient embryos, the allantois was able to fuse with the chorion, but the allantoic mesoderm was abnormally distributed over the chorionic surface. A small number of VCAM-1-deficient embryos survived, presumably by circumventing the placentation defects. They became viable and fertile adult mice with lack of VCAM-1 expression, normal organs, and an elevated number of circulating blood mononuclear leukocytes.

Two-team synchronous oesophagectomy.

Between 1984 and 1992, 131 patients underwent two-team synchronous oesophagectomy for carcinoma. Some 95 per cent of tumours were successfully resected by this technique. In 5 per cent of patients the tumour was found to be irresectable at operation and gastric bypass was performed. The overall operative mortality rate was 8 per cent and the pulmonary complication rate 10 per cent. The actuarial survival rate was 55 per cent at 1 year, 22 per cent at 3 years and 16 per cent at 5 years. When compared with the traditional two-stage Lewis approach, two-team synchronous oesophagectomy was significantly faster (mean 222 versus 282 min), but was not significantly different with respect to blood loss, transfusion requirement, pulmonary complications or operative mortality rate. Patients undergoing two-team oesophagectomy had a significantly shorter hospital stay than those receiving the two-stage procedure (mean 16 versus 24 days).

Low density lipoprotein undergoes oxidative modification in vivo.

It has been proposed that low density lipoprotein (LDL) must undergo oxidative modification before it can give rise to foam cells, the key component of the fatty streak lesion of atherosclerosis. Oxidation of LDL probably generates a broad spectrum of conjugates between fragments of oxidized fatty acids and apolipoprotein B. We now present three mutually supportive lines of evidence for oxidation of LDL in vivo: (i) Antibodies against oxidized LDL, malondialdehyde-lysine, or 4-hydroxynonenal-lysine recognize materials in the atherosclerotic lesions of LDL receptor-deficient rabbits; (ii) LDL gently extracted from lesions of these rabbits is recognized by an antiserum against malondialdehyde-conjugated LDL; (iii) autoantibodies against malondialdehyde-LDL (titers from 512 to greater than 4096) can be demonstrated in rabbit and human sera.

Improved static lung preservation with corticosteroids and hypothermia.

With methylprednisolone as a chemical inhibitor of leukocytes, extended preservation was conducted with an isolated rabbit lung model. The heart-lung blocks of 39 New Zealand white rabbits were flushed in situ with 100 ml of Euro-Collins' solution, harvested, inflated (70%), and preserved at 4 degrees C. Lungs immediately reperfused with whole blood (control lungs, group 1) were compared with lungs preserved without methylprednisolone for 5, 12, and 24 hours (groups 2 to 4) and those preserved with methylprednisolone for 12 and 24 hours (groups 5 and 6, respectively). Methylprednisolone (30 mg/kg) was administered before harvest and was used as an additive to the flush and in the blood reperfusate. Hypothermia and Euro-Collins' flush alone provided adequate preservation for up to 5 hours; however, lung edema was evident by 12 hours of cold ischemia and became severe by 24 hours. By all measured parameters, the lungs in group 5 (treated with methylprednisolone) demonstrated values equal to or better than control lungs. By 24 hours of preservation the beneficial effects of the steroid treatment were no longer evident. Histologic evaluation revealed mild to moderate injury after 5 hours of cold ischemia; progressive edema and hemorrhage were found after 12 and 24 hours of preservation. This injury was significantly ameliorated by methylprednisolone treatment at 12 hours but not at 24 hours. This study suggests that static preservation for up to 5 hours is possible with hypothermia and a Euro-Collins' flush and that extended preservation to 12 hours is possible with pharmacologic dosages of methylprednisolone.(ABSTRACT TRUNCATED AT 250 WORDS)