Compósito biológico-sintético reconstrói tecidos danificados

O material, um composto de moléculas biológicas e sintéticas, é injetado em forma líquida sob a pele e curado com luz, adquirindo o formato definitivo.

Reconstituição de tecidos

Engenheiros biomédicos desenvolveram um novo material líquido para substituir tecidos moles do corpo humano danificados em lesões muito graves.

Nos primeiros experimentos, já realizados in vivo, o material se mostrou promissor no restabelecimento dos tecidos moles danificados, sobretudo por ser muito duradouro.

O material, um composto de moléculas biológicas e sintéticas, é injetado sob a pele.

Em seguida, ele é curado usando a luz para formar uma estrutura mais sólida - de forma semelhante a usar o frio da geladeira para dar a consistência final a uma gelatina.

Compósito biológico-sintético

"Materiais biológicos implantados podem imitar a textura do tecido mole, mas geralmente eles são dissolvidos pelo próprio corpo rápido demais, enquanto os materiais sintéticos tendem a ser mais permanente, mas podem ser rejeitados pelo sistema imunológico e, normalmente, não se fundem bem com os tecidos circundantes naturais," explica Jennifer Elisseeff, da Universidade Johns Hopkins, nos Estados Unidos.

"Nosso material compósito tem o melhor dos dois mundos, com o componente biológico aumentando a compatibilidade com o corpo, e o componente sintético contribuindo para sua durabilidade."

Os pesquisadores criaram o material compósito usando ácido hialurônico, um componente natural que dá elasticidade à pele, e polietileno glicol (PEG), uma molécula sintética usada como cola cirúrgica e bem conhecido por não causar reações imunológicas graves.

O PEG forma ligações químicas resistentes e intercruzadas entre muitas moléculas individuais, aprisionando com ele as moléculas de ácido hialurônico. Essa reação é induzida pela luz.

Essas ligações cruzadas mantêm o formato do implante, evitando que ele fuja do local onde é aplicado.

Reconstrução da face

Os pesquisadores advertem que o novo material, descrito em um artigo na revista Science Translational Medicine, é "promissor", mas ainda não está pronto para uso clínico.

"Ainda temos de avaliar a persistência e a segurança do nosso material em outros tipos de tecidos humanos, como músculos ou regiões menos adiposas sob a pele do rosto, para que possamos otimizá-lo para procedimentos específicos", diz Elisseeff.

Elisseeff disse que a equipe está particularmente esperançosa com o uso do novo compósito em pessoas com deformidades faciais graves, que sofrem trauma social e psicológico.

Na reconstrução de tecidos moles, a recriação da forma natural, sobretudo do rosto, muitas vezes requer múltiplas cirurgias e pode resultar em cicatrizes.

Potential New Eye Tumor Treatment Discovered

ScienceDaily (Aug. 7, 2011) — New research from a team including several Carnegie scientists demonstrates that a specific small segment of RNA could play a key role in the growth of a type of malignant childhood eye tumor called retinoblastoma. The tumor is associated with mutations of a protein called Rb, or retinoblastoma protein. Dysfunctional Rb is also involved with other types of cancers, including lung, brain, breast and bone.

A close-up picture of retinoblastoma cells stained with two retinoblastoma markers.

Their work, which will be the cover story of the August 15th issue ofGenes & Development, could result in a new therapeutic target for treating this rare form of cancer and potentially other cancers as well.

MicroRNAs are a short, single strands of genetic material that bind to longer strands of messenger RNA--which is the courier that brings the genetic code from the DNA in the nucleus to the cell's ribosome, where it is translated into protein. This binding activity allows microRNAs to silence the expression of select genes in a targeted manner. Abnormal versions of microRNAs have been implicated in the growth of several types of cancer.

The paper from Carnegie's Karina Conkrite, Maggie Sundby and David MacPherson--as well as authors from other institutions -- focuses on a cluster of microRNAs called miR-17~92. Recent research has shown that aberrant versions of this cluster are involved in preventing pre-cancerous cells from dying and allowing them to proliferate into tumors. Previous work has shown that miR-17~92 can be involved in the survival of lymphoma and leukemia cells by reducing the levels of a tumor-suppressing protein called PTEN.

The team's new research shows that miR-17~92 can also be involved in retinoblastoma, although it does not act in the same way, via the PTEN protein, as it does in other types of cancers. Rather, miR-17~92 acts to help cells that lack the tumor-suppressing Rb protein to proliferate.

First the team demonstrated that miR-17~92 is expressed in higher-than-usual quantities in all human retinoblastomas examined and in some mouse retinoblastomas. The authors engineered mice to express high levels of miR-17~92 in their retinas. When coupled with inactivation of Rb family members, expression of miR-17~92 led to extremely rapid and aggressive retinoblastoma. Then they showed that this abundance of miR-17~92 acts to suppress an inhibitor of proliferation, called p21Cip1, which is supposed to compensate for the loss of Rb.

"These findings -- which show that miR-17~92 overcomes the cell's attempts to compensate for the loss of Rb -- could be similar in other types of cancers," MacPherson said. "This microRNA cluster could represent a new therapeutic target for treating tumors caused by Rb deficiency."

Frequent Mutations of Chromatin Remodeling Genes Discovered in Transitional Cell Carcinoma of the Bladder

ScienceDaily (Aug. 7, 2011) — BGI, the world's largest genomics organization, Peking University Shenzhen Hospital and Shenzhen Second People's Hospital, announced on August 7 that the study on frequent mutations of chromatin remodeling genes in transitional cell carcinoma (TCC) of the bladder was published online in Nature Genetics. This study provides a valuable genetic basis for future studies on TCC, suggesting that aberration of chromatin regulation might be one of the features of bladder cancer.

Bladder cancer is the ninth most common type of cancer worldwide, which affects three times as many men as women. Almost all bladder cancers originate in the urothelium, so they are also known as one of the most common tumors of the genitourinary tract. Each year, about 360,000 new cases of bladder cancer are expected, and about 150,000 people will die of this disease in the world. In North America, South America, Europe, and Asia, TCC is the most common type of bladder cancer diagnosed, accounting for 90% of all bladder malignancies in those regions.

"Considering the high risks of TCC and the lack of comprehensive analysis, we and our partners initiated this project to identify other previously unidentified genes associated with the bladder cancer." said Professor Zhiming Cai, President of Shenzhen Second People's Hospital and the former President of Peking University Shenzhen Hospital. "I hope our unexpected discoveries in this study can provide more important insights into potential diagnoses and the therapeutic applications." he added.

In this study, the exomes of nine patients with TCC were sequenced with BGI's exome sequencing platform. Then, all the somatically mutated genes were screened in a prevalence set of 88 additional patients with TCC at different tumor stages and grades. "After the detections and statistical analysis, we discovered 49 new significantly mutated genes associated with TCC, and these genes are previously unknown to be mutated in TCC." said Professor Yaoting Gui，the co-leading author of the study and Vice-Director of the Institute of Urology at Peking University Shenzhen Hospital, "Another interesting finding is that eight genes among them are associated with chromatin remodeling, which could be related with frequent mutations in the majority of TCCs."

"We identified the genetic aberrations of the chromatin remodeling genes in 59% of the 97 individuals with TCC, and discovered one gene, UTX, could be altered substantially more frequently in tumors with low stages and grades." said Guangwu Guo, one of the co-leading authors of the study and PI of this project at BGI. "This study indicates UTX may pose a potential role in the classification and diagnosis of bladder cancer."

As we all know, aberrations of the chromatin remodeling genes may directly lead to the misregulation of multiple downstream effector genes, consequently promoting the tumor genesis process. "In our study, the newly discovered genetic mutations in the chromatin remodeling genes, except for UTX, are previous unknown in the primary tumors of TCC." said professor Cai. "Our results demonstrate that the disruption of the chromatin remodeling machinery may be one of the main mechanisms that lead to TCC."

Professor Jun Wang, Executive Director of BGI, said, "This study provides further understanding of bladder cancer and other human cancers through the comprehensive analysis of genetic alterations in TCC. It also implicates the necessity to enhance the epigenomics research in the field of cancer studies in the future. "