Irradiation after immediate tissue expander/implant breast reconstruction: outcomes, complications, aesthetic results, and satisfaction among 156 patients

Chest wall irradiation is becoming increasingly common for mastectomy patients who have opted for immediate breast reconstruction with tissue expanders and implants. The optimal approach for such patients has not yet been defined. This study assesses the outcomes of a reconstruction protocol for patients who require irradiation after tissue expander/implant reconstruction. The charts of all patients who underwent immediate tissue expander/implant reconstruction at Memorial Sloan-Kettering Cancer Center between January of 1995 and June of 2001 and who had not previously undergone irradiation were retrospectively reviewed. A subgroup of patients who required chest wall irradiation after mastectomy and reconstruction was identified. Those patients were treated according to the following treatment algorithm: (1) reconstruction with tissue expander placement at the time of mastectomy , (2) tissue expansion during postoperative chemotherapy, (3) exchange of the tissue expander for a permanent implant approximately 4 weeks after the completion of chemotherapy, and (4) chest wall irradiation beginning 4 weeks after the exchange. All irradiated patients with at least 1 year of follow-up monitoring after the completion of radiotherapy were evaluated with respect to aesthetic outcomes, capsular contracture, and patient satisfaction. A control group of nonirradiated patients was randomly selected from the cohort of patients treated during the study period. During the 5-year study period, a total of 687 patients underwent immediate reconstruction with tissue expanders. Eighty-one patients underwent postoperative irradiation after placement of the final implant. A total of 68 patients who received postoperative chest wall irradiation underwent at least 1 year of follow-up monitoring after the completion of radiotherapy, with a mean follow-up period of 34 months. Seventy-five nonirradiated patients were evaluated as a control group. Overall, 68 percent of the irradiated patients developed capsular contracture, compared with 40 percent in the nonirradiated group (p = 0.025). Eighty percent of the irradiated patients demonstrated acceptable (good to excellent) aesthetic results, compared with 88 percent in the nonirradiated group (p = not significant). Sixty-seven percent of the irradiated patients were satisfied with their reconstructions, compared with 88 percent of the nonirradiated patients (p = 0.004). Seventy-two percent of the irradiated patients stated that they would choose the same form of reconstruction again, compared with 85 percent of the nonirradiated patients. The results of this study suggest that tissue expander/implant reconstruction is an acceptable surgical option even when followed by postoperative radiotherapy and should be considered in the reconstruction algorithm for all patients, particularly those who may not be candidates for autogenous reconstruction.     

Kinetics of chondrocyte growth in cell-polymer implants

In vitro cultivation of cartilage cells (chondrocytes) on biodegradable polyglycolic acid (PGA) scaffolds resulted in implants which could potentially be used to repair damaged joint cartilage or for reconstructive surgery. Cell growth kinetics were studied to define conditions under which the cellularity of implants made from isolated calf chondrocytes reached that of the parent calf cartilage. In static cultures, condrocyte growth rates decreased as either implant thickness or implant cell density increased. Over 4 weeks of cultivation, implant permeability to glucose decreased to 3% that of the plain polymer scaffold; this effect was attributed to the decrease in effective implant porosity associated with cartilage tissue regeneration.In a well-mixed culture, implants 1 cm in diameter by 0.3 cm thick maintained high cell growth rates over 7 weeks and hard normal cell densities. Regenerated cartilage with these dimensions is large enough to resurface small joints such as the trapezium bone at the base of the human thumb. Such implants could not be grown statically, since cell growth stopped at 3-4 weeks and cell densities remained below normal. Optimization of the tissue culture environment is thus essential in order to cultivate clinically useful cartilage implants in vitro. (c) 1994 John Wiley & Sons, Inc.     

Characteristics of cartilage engineered from human pediatric auricular cartilage

In the repair of cartilage defects, autologous tissue offers the advantage of lasting biocompatibility. The ability of bovine chondrocytes isolated from hyaline cartilage to generate tissue-engineered cartilage in a predetermined shape, such as a human ear, has been demonstrated; however, the potential of chondrocytes isolated from human elastic cartilage remains unknown. In this study, the authors examined the multiplication characteristics of human auricular chondrocytes and the ability of these cells to generate new elastic cartilage as a function of the length of time they are maintained in vitro. Human auricular cartilage, harvested from patients 5 to 17 years of age, was digested in collagenase, and the chondrocytes were isolated and cultured in vitro for up to 12 weeks. Cells were trypsinized, counted, and passaged every 2 weeks. Chondrocyte-polymer (polyglycolic acid) constructs were created at each passage and then implanted into athymic mice for 8 weeks. The ability of the cells to multiply in vitro and their ability to generate new cartilage as a function of the time they had been maintained in vitro were studied. A total of 31 experimental constructs from 12 patients were implanted and compared with a control group of constructs without chondrocytes. In parallel, a representative sample of cells was evaluated to determine the presence of collagen. The doubling rate of human auricular chondrocytes in vitro remained constant within the population studied. New tissue developed in 22 of 31 experimental implants. This tissue demonstrated the physical characteristics of auricular cartilage on gross inspection. Histologically, specimens exhibited dense cellularity and lacunae-containing cells embedded in a basophilic matrix. The specimens resembled immature cartilage and were partially devoid of the synthetic material of which the construct had been composed. Analyses for collagen, proteoglycans, and elastin were consistent with elastic cartilage. No cartilage was detected in the control implants. Human auricular chondrocytes multiply well in vitro and possess the ability to form new cartilage when seeded onto a three-dimensional scaffold. These growth characteristics might some day enable chondrocytes isolated from a small auricular biopsy to be expanded in vitro to generate a large, custom-shaped, autologous graft for clinical reconstruction of a cartilage defect, such as for congenital microtia.     

Histologic and histomorphometric follow-up observations of osseointegration of corundum-blasted BMP-3 coated titanium test implants (Ti6Al4V) at orthotopic site in the giant rabbit]

AIM: To establish whether the additional coating of titanium implants with Bone Morphogenetic Protein-3 (BMP-3) might enhance osseous integration. METHOD: Each of 15 cylindrical titanium test implants (Ti-6AI-4V) was coated using 230 micrograms porcine BMP-3. A further 15 implants with identical (corundium-blasted) surface served as negative controls. An uncoated and a BMP-3-coated test object were implanted into the femurs of 15 adult giant rabbits. New formation of bone around the implants was examined microscopically and histomorphometrically on postoperative days 14, 35 and 56. RESULTS: Coated implants revealed superior osseointegration with statistical evaluation using the t-test for matched samples showing a significantly higher volume of new bone 5 weeks after surgery. Microscopic examination revealed osseointegration with no connective tissue membrane around the surface of the implants. CONCLUSIONS: Our results indicate that composite metal implants are suitable carriers for BMP-3 and that improved fixation of the implants can be achieved.     

An Animal Explant Model for the Study of Human Cutaneous Squamous Cell Carcinoma

We established a human tissue explant model to facilitate study of cutaneous squamous cell carcinoma. We accomplished this by implanting debulked SCC, from surgical discard, into nude rats. Human SCC remained viable and continued to proliferate for at least 4 weeks and showed evidence of neovascularization. At 4 weeks, SCC implants showed a trend toward increased PCNA positive cells compared to fresh SCC cells/mm² tissue) supporting continued proliferation throughout engraftment. Von Willebrand''s Factor (VWF) positive cells were found within implants and likely represented rat vessel neovascularization. Human Langerhans'' (Langerin+) cells, but no T cells (CD3+, CD8+, FoxP3+), macrophages (CD163), or NK cells (NKp46), were present in SCC implants at 4 weeks. These findings support the possibility that LCs fail to migrate from cutaneous SCC and thus contribute to lack of effective antitumor response. Our findings also provide a novel model system for further study of primary cutaneous SCC.     

冲击波诱导人骨髓基质细胞体内成骨研究

为了研究冲击波(SW)诱导人骨髓基质细胞(hMSCs)在动物体内成骨作用,根据前期工作结果,应用适宜能量冲击波(10kV,500次)处理体外培养的hMSCs,将SW组和对照组hMSCs与羟基磷灰石(HA)载体复合后体外培养2周,应用扫描电镜(SEM)检测细胞在载体表面的生长情况.将hMSCs-HA载体复合体植入裸鼠皮下,分别于术后4周、8周取材进行组织学、四环素荧光标记、SEM观察、碱性磷酸酶测定、RT-PCR检测骨钙素mRNA表达.结果表明,SW组及对照组细胞与HA载体体外复合后生长良好,且SW组细胞分泌较多的细胞基质;细胞载体复合体植入动物体内后,SW组载体表面有类骨组织形成,而对照组HA载体表面无骨组织形成;SW组与对照组的hMSCs-HA载体复合体碱性磷酸酶表达有显著性差异(P<0.01);SW组hMSCs-HA载体复合体术后4周与8周表达骨钙素mRNA,而对照组则无表达.提示hMSCs经适宜能量冲击波作用后与HA载体复合植入裸鼠体内具有成骨作用,适宜能量的冲击波作为一种新的促进hMSCs成骨分化的方法,可应用于组织工程领域.     

Prognostic significance of TP53 mutations in oral squamous cell carcinoma with human papilloma virus infection

PURPOSE: The aim of this study was to analyze the prognostic impact of mutated TP53 in patients with oral squamous cell carcinoma (OSCC) whose tumors were infected with human papillomavirus (HPV). METHODS: Thirty-two HPV-positive OSCC patients were included. Most of them were clinically classified as stage III (n=29). All patients underwent postoperative radiotherapy (follow-up from 12 to 60 months, median 32). There were 21 relapses. DNA was isolated by phenol extraction from tumor tissue. HPV DNA (type 16, 18, 31, 33) was detected in genomic DNA of the tumors by the PCR-PAGE method. TP53 mutations (exons 4-8) were detected by the PCR-SSCP method. RESULTS: A statistically significant difference in the number of relapses in HPV-infected (13/21) versus HPV-infected and TP53-mutated (8/8) patients was observed. Patients with both TP53 mutation and HPV infection had a significantly shorter disease-free interval than patients with HPV infection only (median 6 versus 31 months, respectively). CONCLUSIONS: TP53 mutations are associated with a higher risk of relapse and contribute to an even worse prognosis of patients with OSCC when the tumors are HPV infected. The shorter disease-free interval in patients with TP53 mutations indicates that the response to postoperative radiotherapy may be influenced by TP53 status. The presence of both HPV infection and TP53 mutations may define a particular group of tumors with a more aggressive phenotype in advanced OSCC.     

Hair multiplication with dermal papilla like tissue containing human dermal papilla cells

Alopecia is not a critical disease; however it is a disease that can affect the quality of life. Many remedies have been developed to cure alopecia, but only two have been approved by the FDA. Due to the steadily increasing number of young alopecia patients, the need for new therapies for curing alopecia is very high. Recent studies on cell therapy have reported using technique to treat various diseases. We introduce upgraded hair cell therapy which tested hair structure inducing activity with bioartificial dermal papilla tissue. Hair follicles contain two types of stem cells: Outer root sheath cells (ORSCs) derived epithelial cells, and dermal cells (DPCs). In this study, we reconstructed DP-like tissues (DPLTs) using cultured dermal papilla cells (DPCs) from human hair follicles. The DPLTs were produced special media (Dermal Papilla Forming Media: DPFM) conditions in vitro, which can induce epithelial stands from implanted healthy hair without DP. We tested in vivo hair-inducing with a modified hair sandwich model. Two to three weeks DPLT injection into the mouse scalp skin, we observed new hair in the injected site and detected injected human cells from DPLTs and Outer Root Sheath Cells (ORSCs) in the new hair via human Alu-DNA-specific probe. In the future, reconstructed DPLTs may be used in in vitro studies of hair development and the morphogenesis mechanism, as well as in vitro studies of the efficacy and toxicity of drugs for baldness. These tissues will be used as an alternative medicine product for hair transplantation     

Analysis of silicon in human tissues with special reference to silicone breast implants

The increase, in the last two decades, in the application of silicones (polysiloxanes) and inorganic silicon compounds in medicine and the food industry, has exposed the human body to extensive contacts with these substances. Most silicone breast implants contain a gel consisting of a crosslinked silicone elastomer swollen by silicone oil (PDMS). Diffusion of PDMS through the silicone elastomer envelope and rupture of the envelope with release of the gel contents both occur clinically. The amount and distribution of silicone compounds in various tissues are key issues in the assessment of health problems connected with silicone implants. We have measured by GFAAS the Si content of tissues from normal and implant patients and the organic solvent extractable Si levels (assumed to be silicone), using careful control of sample collection and preparation. Whole blood levels were: implant patients mean 38.8 (SD 25.6) (microg/kg), controls mean 24.2 (SD 26.7) (microg/kg) in one study and subsequently 103.8 (SD 112.1) and 74.3 (SD 86.5) (microg/kg) in another study. Capsular tissue levels were: gel implants 25047 (SD 39313) (mg/kg of dry tissue), saline implants 20.0 (SD 27.3) (mg/kg of dry tissue) and controls 0.24 (SD 0.39) (mg/kg of dry tissue). Breast milk levels were: implant patients mean 58.7 (SD 33.8) (microg/kg), controls mean 51.1 (SD 31.0) (microg/kg); infant formula mean was 4.40 (mg/kg). Various precautions were undertaken to avoid Si contamination in this work, the most important being a) the use of a Class 100 laboratory for sample preparation and b) application of strict and elaborate washing procedure for specimen collection tools and laboratory plasticware. This data demonstrated that to properly interpret the importance of these numbers for human health, a larger study of "normal" levels of Si in human tissues should be undertaken and factors such as diet, water, race and geographical location should be considered.     

Anti-cancer activities of tea epigallocatechin-3-gallate in breast cancer patients under radiotherapy

The purpose of this study was to test the hypothesis that administration of epigallocatechin-3-gallate (EGCG), a polyphenol present in abundance in widely consumed tea, inhibits cell proliferation, invasion, and angiogenesis in breast cancer patients. EGCG in 400 mg capsules was orally administered three times daily to breast cancer patients undergoing treatment with radiotherapy. Parameters related to cell proliferation, invasion, and angiogenesis were analyzed while blood samples were collected at different time points to determine efficacy of the EGCG treatment. Compared to patients who received radiotherapy alone, those given radiotherapy plus EGCG for an extended time period (two to eight weeks) showed significantly lower serum levels of vascular endothelial growth factor (VEGF), hepatocyte growth factor (HGF), and reduced activation of metalloproteinase-9 and metalloproteinase-2 (MMP9/MMP2). Addition of sera obtained from patients treated with combination of radiotherapy and EGCG feeding for 2-8 weeks to in vitro cultures of highly-metastatic human MDA-MB-231 breast cancer cells resulted in the following significant changes: (1) suppression of cell proliferation and invasion; (2) arrest of cell cycles at the G0/G1 phase; (3) reduction of activation of MMP9/MMP2, expressions of Bcl-2/Bax, c-Met receptor, NF-κB, and the phosphorylation of Akt. MDA-MB-231 cells exposed to 5-10 μM EGCG also showed significant augmentation of the apoptosis inducing effects of γ-radiation, concomitant with reduced NF-κB protein level and AKT phosphorylation. These results provide hitherto unreported evidence that EGCG potentiated efficacy of radiotherapy in breast cancer patients, and raise the possibility that this tea polyphenol has potential to be a therapeutic adjuvant against human metastatic breast cancer.     

Autogenous augmentation mammaplasty with microsurgical tissue transfer

Many patients dream of reducing their abdominal or gluteal fat tissue and, in the same procedure, enlarging their breasts without the need for implants and their related problems. Following this demand, a new "natural" alternative to breast augmentation with autogenous tissue is presented. Since 1993, 16 patients have undergone either unilateral or bilateral breast augmentation with free fat transfer. These 20 augmentation mammaplasties consisted of nine deep inferior epigastric perforator flaps, eight superior gluteal artery perforator flaps, and three superficial inferior epigastric artery flaps. The postoperative results were judged aesthetically by independent examiners and by the patients according to Netscher's score. The additional operations for final shaping of the breasts and the postoperative complications at the donor and recipient sites are reported. The augmented breasts improved the aesthetic proportions more than 100 percent. All flaps survived, and except for minor postoperative complications such as small areas of wound dehiscence, the breasts could be shaped aesthetically in a second-stage procedure several weeks later. Breast augmentation with autogenous tissue offers a natural alternative to alloplastic augmentation mammaplasty.     

The role of radiotherapy in the prevention of recurrence and central nervous system metastases in childhood medulloblastoma

PURPOSE: To present the postoperative radiotherapy technique in children with medulloblastoma, and analyse the effectiveness of radiotherapy and the survival data. MATERIALS AND METHODS: 66 consecutive children (45 male and 21 female) received postoperative chemotherapy and radiotherapy between 1986 and 1998. The mean age was 8.3 years. The radiotherapy was performed with linear accelerator 9MV X-ray irradiation. The high risk patients received 36 Gy craniospinal irradiation, the low risk patients recived 30 Gy. The boost irradiation to the posterior fossa was 20 Gy in both patient groups. The patients received multi-drug chemotherapy immediately after the tumor resection. The radiotherapy started 6-8 weeks after the operation. RESULTS: All 66 patients were evaluated. The mean follow-up time was 45.4 months. The chance of cure is higher at age 8 or more, and less favorable under age 8. After 60 months 68.6% of children under age 8 and 75.9% older than 8 are alive. 20 children (64.5%) are alive after radical tumorectomy and 11 died. The 5 year overall survival was 71%. Recurrence was observed in 23/66 cases, it was the most frequent cause of death. Local failure was in posterior fossa in 15 patients (68.2%). CONCLUSION: The radicality of operation had no significant influence to the overall survival. The tumor stage, age of patients, risk group and metastases are important prognostic factors.     

The Use of Biodegradable Implants in the Fixation of Small Animal Cancellous Bone Fractures

In this study the cancellous bone fractures of 10 dogs and 2 cats were surgically treated with biodegradable implants to fixate the fractures. The implants were made of selfreinforced PGA homopolymers. The patients were allowed to walk on their operated limbs immediately after the fixation and they started to use them within one week. All patients except one used their operated limbs without lameness in 6 weeks and the twelfth case in 8 weeks, due to a postoperative periosteal infection. Radiographically, the fractures of 10 patients healed in 6 weeks and in 12 weeks in 2 cases. No other pathological reactions in the bone could be seen in the radiographs than the periosteal infection. Because the implants resolved spontaneously there was no need for a second operation to remove them.     

Foetal hepatocyte transplantation in a vascularized AV-Loop transplantation model in the rat

The use of foetal liver cells (FLC) in the context of hepatic tissue engineering might permit efficient in vitro expansion and cryopreservation in a cell bank. A prerequisite for successful application of bioartificial liver tissue is sufficient initial vascularization. In this study, we evaluated the transplantation of fibrin gel-immobilized FLC in a vascularized arterio-veno-venous (AV)-loop model. FLC were isolated from embryonic/foetal (ED 16) rat livers and were enriched by using magnetic cell sorting (MACS). After cryopreservation, FLC were labelled by pkh-26. Cells were transplanted in a fibrin matrix into a subcutaneous chamber containing a microsurgically created AV-loop in the femoral region of the recipient rat. The chambers were explanted after 14 days. Subcutaneous implants without an AV-loop and cell-free implants served as controls. Fluorescence microscopy of the constructs was used to identify pkh-26⁺- donor cells. Characterization was performed by RT-PCR and immunhistology (IH) for CK-18 and CD31. Transplantation of FLC using the AV-loop permitted a neo -tissue formation in the fibrin matrix. A high-density vascularization was observed in the AV-loop constructs as shown by CD31 IH. Viable foetal donor cells were detected which expressed CK-18. FLC can be successfully used for heterotopic transplantation. Fibrin matrix permits rapid blood vessel ingrowth from the AV-loop and supports engraftment of FLC. It is therefore an appropriate environment for hepatocyte transplantation in combination with microsurgical vascularization strategies. Transplantation of fibrin gel-immobilized FLC may be a promising approach for the development of highly vascularized in vivo tissue-engineering-based liver support systems.     

Aptamer-based capture molecules as a novel coating strategy to promote cell adhesion

The improvement of the cytocompatibility of medical implants is a major goal in biomaterials research. During the last years many researchers worked on the fascinating approach to seed the respective cell types on various artificial substrates before implantation. For instance, cell-seeded implants are supposed to be better candidates for transplantable bone substitutes than conventional artificial bone grafts. To improve cell seeding efficiency and cytocompatibility, we designed a new coating material for medical implants. We used aptamers, highly specific cell binding nucleic acids generated by combinatorial chemistry with an in vitro selection called systematic evolution of exponential enrichment (SELEX). Aptamers do have high binding affinity and selectivity to their target. In our study, human osteoblasts from osteosarcoma tissue were used as a target to create the aptamer. Single aptamer mediated cell sorting assays showed the binding affinity with osteoblasts. Additionally, the aptamers immobilized on tissue culture plates could capture osteoblasts directly and rapidly from the cell solution. This model proves that aptamer coated artificial surfaces can greatly enhance cell adhesion. We assume that this strategy is capable to improve the clinical application of tissue engineered implants.     

Osteoradionecrosis of the mandible after oromandibular cancer surgery

Although postoperative radiotherapy has proved effective in improving local control and survival in patients with head and neck cancers, its complications, especially mandibular osteoradionecrosis, reduce the quality of life. Mandibular surgery before the radiotherapy adds an additional risk factor for osteoradionecrosis. This study reviews patients in Chang Gung Memorial Hospital, Taipei, Taiwan, over a 10-year period, who underwent intraoral cancer resection followed by postoperative radiotherapy and thereafter developed osteoradionecrosis of the mandible. A total of 24 men and three women with a mean age of 49.9 years were identified and included in the study. In 10 cases, tumor resection was performed with a marginal mandibulectomy; in eight cases, tumor resection was performed after mandibular osteotomy; and in three cases, a segmental mandibulectomy was performed, and the defect was reconstructed with a fibula osteoseptocutaneous flap. In six cases, tumor excisions were performed without interfering with the mandibular continuity. Patients received postoperative external beam radiotherapy into the primary site and the neck, with a mean dose (+/-SD) of 5900 +/- 1300 cGy in an average of 35 fractions during an average of 6.5 weeks. The average elapsed time between the end of radiation therapy and clinical diagnosis of osteoradionecrosis of the mandible was 11.2 months (range, 2 to 36 months). The time elapse between the end of the radiation therapy and the diagnosis of osteoradionecrosis was influenced by initial treatment (Kruskal-Wallis test: n = 27, chi-square = 12.884, p < 0.005), and this period was shorter if the mandibular osteotomy or marginal mandibulectomy was performed (the two lowest mean ranks in the test). However, if the initial surgery resulted in a segmental mandibulectomy reconstructed with a fibula osteoseptocutaneous flap, onset of the osteoradionecrosis was relatively late (Kruskal-Wallis test: n = 21, chi-square = 7.731, p = 0.052). After resection of osteoradionecrotic bone and surrounding soft tissue, 22 patients underwent reconstructive procedures with a fibula osteoseptocutaneous flap, and five patients underwent reconstructive procedures with an inferior genicular artery osteoperiosteal cutaneous flap. One fibula osteoseptocutaneous flap showed total failure and another showed a 25 percent skin loss; both were revised with pedicled flaps. The skin paddle of an inferior genicular artery flap was replaced with an anterolateral thigh flap because of anatomic variation of the skin vessel. Once the diagnosis of osteoradionecrosis is established, replacement of the dead bone and surrounding tissue with a vascularized free bone flap is inevitable, and a composite osteocutaneous free flap is a good option.     

种植体稳定系数测定与种植体负重时机选择

目的:通过测量ITI和Osstem-SS种植系统的稳定系数(ISQ),评价这两种种植体的骨结合情况,为临床确定其上部结构修复时机提供依据。方法:93例牙列缺损患者共植入179颗种植体,根据患者种植区骨量情况分为两组,其中A组为种植区骨量良好,不需骨增量手术病例(62例);B组为种植区骨量不足,需进行骨增量手术病例(31例)。A组共植入125颗种植体,其中ITI种植系统64颗,OSSTEM-SS种植系统61颗;B组共植入54颗种植体,其中ITI种植系统28颗,OSSTEM-SS种植系统26颗。术后即刻及第4、6、8、12、16、24周分别测量各时期种植体稳定系数(ISQ),并同期进行临床和影像学检查。结果:A组中ITI种植系统术后8周ISQ值平均(74.17±1.85),进行负重;OSSTEM-SS种植系统术后12周ISQ值平均(72.00±2.59),进行负重。B组中ITI种植系统术后16周ISQ值平均(65.09±3.42),进行负重;OSSTEM-SS种植系统术后24周ISQ值平均(62.09±6.16),进行负重。负重后临床随访3-24个月所有病例均成功,咀嚼功能良好,患者满意。结论:种植体稳定系数(ISQ)能反应种植体骨结合情况,可以协助医生选择种植后合适的冠修复时机。     

Tissue engineering in otorhinolaryngology

Tissue engineering is a field of research with interdisciplinary cooperation between clinicians, cell biologists, and materials research scientists. Many medical specialties apply tissue engineering techniques for the development of artificial replacement tissue. Stages of development extend from basic research and preclinical studies to clinical application. Despite numerous established tissue replacement methods in otorhinolaryngology, head and neck surgery, tissue engineering techniques opens up new ways for cell and tissue repair in this medical field. Autologous cartilage still remains the gold standard in plastic reconstructive surgery of the nose and external ear. The limited amount of patient cartilage obtainable for reconstructive head and neck surgery have rendered cartilage one of the most important targets for tissue engineering in head and neck surgery. Although successful in vitro generation of bioartificial cartilage is possible today, these transplants are affected by resorption after implantation into the patient. Replacement of bone in the facial or cranial region may be necessary after tumor resections, traumas, inflammations or in cases of malformations. Tissue engineering of bone could combine the advantages of autologous bone grafts with a minimal requirement for second interventions. Three different approaches are currently available for treating bone defects with the aid of tissue engineering: (1) matrix-based therapy, (2) factor-based therapy, and (3) cell-based therapy. All three treatment strategies can be used either alone or in combination for reconstruction or regeneration of bone. The use of respiratory epithelium generated in vitro is mainly indicated in reconstructive surgery of the trachea and larynx. Bioartificial respiratory epithelium could be used for functionalizing tracheal prostheses as well as direct epithelial coverage for scar prophylaxis after laser surgery of shorter stenoses. Before clinical application animal experiments have to prove feasability and safety of the different experimental protocols. All diseases accompanied by permanently reduced salivation are possible treatment targets for tissue engineering. Radiogenic xerostomia after radiotherapy of malignant head and neck tumors is of particular importance here due to the high number of affected patients. The number of new diseases is estimated to be over 500,000 cases worldwide. Causal treatment options for radiation-induced salivary gland damage are not yet available; thus, various study groups are currently investigating whether cell therapy concepts can be developed with tissue engineering methods. Tissue engineering opens up new ways to generate vital and functional transplants. Various basic problems have still to be solved before clinically applying in vitro fabricated tissue. Only a fraction of all somatic organ-specific cell types can be grown in sufficient amounts in vitro. The inadequate in vitro oxygen and nutrition supply is another limiting factor for the fabrication of complex tissues or organ systems. Tissue survival is doubtful after implantation, if its supply is not ensured by a capillary network.     

Regulation of adipose tissue inflammation and systemic metabolism in murine obesity by polymer implants loaded with lentiviral vectors encoding human interleukin-4

Dysfunctional adipose tissue plays a central role in the pathogenesis of the obesity-related metabolic disease, including type 2 diabetes. Targeting adipose tissue using biopolymer implants is a novel therapeutic approach for metabolic disease. We transplanted porous poly(lactide-co-glycolide) (PLG) implants coated with human interleukin-4 (hIL-4)-expressing lentivirus into epididymal white adipose tissue (eWAT) of mice fed a high-fat diet. Tissue and systemic inflammation and metabolism were studied with flow cytometry, immunohistochemistry, quantitative real-time polymerase chain reaction, adipose tissue histology, and in vivo glucose tolerance testing at 2 and 10 weeks of a high-fat diet. PLG implants carrying hIL-4-expressing lentivirus implanted into epididymal white adipose tissue of mice-regulated adipose tissue inflammation, including increased CD3⁺CD4⁺ T-cell frequency, increased eWAT adipocyte hypertrophy, and decreased FASN and ATGL expression, along with reduced fasting blood glucose levels. These effects were observed in early obesity but were not maintained in established obesity. Local delivery of bioimplants loaded with cytokine-expressing lentivirus vectors to adipose tissue influences tissue inflammation and systemic metabolism in early obesity. Further study will be required to show more durable metabolic effects. These data demonstrate that polymer biomaterials implanted into adipose tissue have the potential to modulate local tissue and systemic inflammation and metabolism.     

Evaluation of Biological Properties of Electron Beam Melted Ti6Al4V Implant with Biomimetic Coating In Vitro and In Vivo

Background

High strength porous titanium implants are widely used for the reconstruction of craniofacial defects because of their similar mechanical properties to those of bone. The recent introduction of electron beam melting (EBM) technique allows a direct digitally enabled fabrication of patient specific porous titanium implants, whereas both their in vitro and in vivo biological performance need further investigation.

Methods

In the present study, we fabricated porous Ti6Al4V implants with controlled porous structure by EBM process, analyzed their mechanical properties, and conducted the surface modification with biomimetic approach. The bioactivities of EBM porous titanium in vitro and in vivo were evaluated between implants with and without biomimetic apatite coating.

Results

The physical property of the porous implants, containing the compressive strength being 163 - 286 MPa and the Young’s modulus being 14.5–38.5 GPa, is similar to cortical bone. The in vitro culture of osteoblasts on the porous Ti6Al4V implants has shown a favorable circumstance for cell attachment and proliferation as well as cell morphology and spreading, which were comparable with the implants coating with bone-like apatite. In vivo, histological analysis has obtained a rapid ingrowth of bone tissue from calvarial margins toward the center of bone defect in 12 weeks. We observed similar increasing rate of bone ingrowth and percentage of bone formation within coated and uncoated implants, all of which achieved a successful bridging of the defect in 12 weeks after the implantation.

Conclusions

This study demonstrated that the EBM porous Ti6Al4V implant not only reduced the stress-shielding but also exerted appropriate osteoconductive properties, as well as the apatite coated group. The results opened up the possibility of using purely porous titanium alloy scaffolds to reconstruct specific bone defects in the maxillofacial and orthopedic fields.