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Welcome to The Visible Embryo, a comprehensive educational resource on human development from conception to birth.

The Visible Embryo provides visual references for changes in fetal development throughout pregnancy and can be navigated via fetal development or maternal changes.

The National Institutes of Child Health and Human Development awarded Phase I and Phase II Small Business Innovative Research Grants to develop The Visible Embryo. Initally designed to evaluate the internet as a teaching tool for first year medical students, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than one million visitors each month.

Today, The Visible Embryo is linked to over 600 educational institutions and is viewed by more than 1 million visitors each month. The field of early embryology has grown to include the identification of the stem cell as not only critical to organogenesis in the embryo, but equally critical to organ function and repair in the adult human. The identification and understanding of genetic malfunction, inflammatory responses, and the progression in chronic disease, begins with a grounding in primary cellular and systemic functions manifested in the study of the early embryo.

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Pregnancy Timeline by SemestersFetal liver is producing blood cellsHead may position into pelvisBrain convolutions beginFull TermWhite fat begins to be madeWhite fat begins to be madeHead may position into pelvisImmune system beginningImmune system beginningPeriod of rapid brain growthBrain convolutions beginLungs begin to produce surfactantSensory brain waves begin to activateSensory brain waves begin to activateInner Ear Bones HardenBone marrow starts making blood cellsBone marrow starts making blood cellsBrown fat surrounds lymphatic systemFetal sexual organs visibleFinger and toe prints appearFinger and toe prints appearHeartbeat can be detectedHeartbeat can be detectedBasic Brain Structure in PlaceThe Appearance of SomitesFirst Detectable Brain WavesA Four Chambered HeartBeginning Cerebral HemispheresFemale Reproductive SystemEnd of Embryonic PeriodEnd of Embryonic PeriodFirst Thin Layer of Skin AppearsThird TrimesterSecond TrimesterFirst TrimesterFertilizationDevelopmental Timeline
CLICK ON weeks 0 - 40 and follow along every 2 weeks of fetal development
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Home | Pregnancy Timeline | News Alerts |News Archive March 14, 2014

 

Tooth-precursor cells in the swollen gel (left) are elongated,
but as the gel warms and compresses, the cells shrink and round
up (right). They also become denser and begin to deposit
the minerals that harden teeth.

Image Credit: Basma Hashmi.



Tooth-precursor gell shrinking

When the temperature rises to just below body temperature, this biocompatible gel shrinks
dramatically within minutes, bringing tooth-precursor cells (green) closer together.

Movie Credit: Basma Hashmi






WHO Child Growth Charts

 

 

 

A gel that repairs bone and may replace teeth

Material inspired by an embryo's power to shape organs could enable doctors to engineer new teeth, bone, or even more tissues. A bit of pressure from a new shrinking, sponge-like gel is all it takes to turn transplanted unspecialized cells into cells that lay down minerals and begin to form teeth.

The bioinspired gel material could one day help repair or replace damaged organs, such as teeth and bone, and possibly other organs as well, scientists from the Wyss Institute for Biologically Inspired Engineering at Harvard University, Harvard School of Engineering and Applied Sciences (SEAS), and Boston Children's Hospital report recently in Advanced Materials.


"Tissue engineers have long raised the idea of using synthetic materials to mimic the inductive power of the embryo. We're excited about this work because it shows that it really is possible."

Don Ingber, M.D., Ph.D., Founding Director of the Wyss Institute, Judah Folkman Professor of Vascular Biology at Harvard Medical School, Professor of Bioengineering at SEAS, and senior author of the study.


A few years ago, Ingber and Tadanori Mammoto, M.D., Ph.D., (instructor in Surgery at Boston Children's Hospital and Harvard Medical School), investigated mesenchymal condensation.


Embryos begin forming a variety of organs, including teeth, cartilage, bone, muscle, tendon, and kidney, on the basis of condensation.

Two tissue layers — connective-tissue cells called mesenchyme and a sheet-like tissue that covers it called epithelium — exchange biochemical signals.

This cross talk drives the mesenchymal cells to form a small knot directly below where the new organ will form.


By examining tissues isolated from the jaws of embryonic mice, Mammoto and Ingber found that when compressed, mesenchymal cells turn on genes that generate whole teeth composed of mineralized tissues, including dentin and enamel.

Inspired by this induction mechanism, Ingber along with Basma Hashmi, a Ph.D. candidate at SEAS — lead author on the current paper — aimed to engineer a tissue-friendly material with the same properties.

To develop such a material, Ingber and Hashmi teamed up with researchers led by Joanna Aizenberg, Ph.D., a Wyss Institute Core faculty member, who leads the Institute's Adaptive Materials Technologies platform. Aizenberg is an Amy Smith Berylson Professor of Materials Science at SEAS, and a professor of chemistry and chemical biology at Harvard University.

With Aizenberg's help, they found a special gel-forming polymer called PNIPAAm. PNIPAAm is used to deliver drugs to tissues in the body. A particuarly property of PNIPAAm gels is that it contracts abruptly when warmed to lukewarm temperature. However, the researchers needed it to shrink at 37°C — which is body temperature — or as soon as it is injected into the body.

Hashmi worked with Lauren Zarzar, Ph.D., a former SEAS graduate student, for more than a year to modify PNIPAAm. Ultimately, they developed a polymer that forms a tissue-friendly gel with two key properties: (1) cells stick to it and (2) it compresses abruptly when warmed to body temperature. In an initial test, Hashmi implanted mesenchymal cells in the gel and warmed it in the lab - and sure enough, when the temperature reached 37°C, the gel shrank causing the cells inside to pack tightly together.

"The reason that's cool is that the cells are alive," Hashmi said. "Usually when this happens, cells are dead or dying."

Not only were they alive — they activated three genes that drive tooth formation.


To see if the gel worked, mesenchymal cells were loaded into it and it was implanted beneath the mouse kidney capsule — an area well supplied with blood and often used in transplant experiments.

The implanted cells not only expressed tooth-development genes — they laid down calcium and minerals, just as mesenchymal cells do in the body before forming teeth.

"They were in full-throttle tooth-development mode," Hashmi added.


In the embryo, mesenchymal cells can't build teeth alone — they need to combine with cells that form the epithelium. In the future, the scientists plan to test whether the shrinking gel can stimulate both tissues to generate an entire functional tooth.

Keywords:
scaffold engineering;biomaterials;odontogenesis;poly(N-isopropylacrylamide);thermoresponsive

Abstract
A biologically inspired thermoresponsive polymer has been developed that mechanically induces tooth differentiation in vitro and in vivo by promoting mesenchymal cell compaction as seen in each pore of the scaffold. This normally occurs during the physiological mesenchymal condensation response that triggers tooth formation in the embryo.

The work was funded by the National Institutes of Health and the Wyss Institute. In addition to Hashmi, Mammoto, Ingber, Aizenberg and Zarzar, the research team also included Akiko Mammoto, Ph.D., Instructor in Surgery at Boston Children's Hospital and Harvard Medical School, and Amanda Jiang, a technician at Boston Children's Hospital.

About the Wyss Institute for Biologically Inspired Engineering at Harvard University

The Wyss Institute for Biologically Inspired Engineering at Harvard University uses Nature's design principles to develop bioinspired materials and devices that will transform medicine and create a more sustainable world. Working as an alliance among all of Harvard's Schools, and in partnership with Beth Israel Deaconess Medical Center, Brigham and Women's Hospital, Boston Children's Hospital, Dana Farber Cancer Institute, Massachusetts General Hospital, the University of Massachusetts Medical School, Spaulding Rehabilitation Hospital, Boston University, Tufts University, and Charité - Universitätsmedizin Berlin, the Institute crosses disciplinary and institutional barriers to engage in high-risk research that leads to transformative technological breakthroughs. By emulating Nature's principles for self-organizing and self-regulating, Wyss researchers are developing innovative new engineering solutions for healthcare, energy, architecture, robotics, and manufacturing. These technologies are translated into commercial products and therapies through collaborations with clinical investigators, corporate alliances, and new start-ups.

About the Harvard School of Engineering and Applied Sciences

The Harvard School of Engineering and Applied Sciences (SEAS) serves as the connector and integrator of Harvard's teaching and research efforts in engineering, applied sciences, and technology. Through collaboration with researchers from all parts of Harvard, other universities, and corporate and foundational partners, we bring discovery and innovation directly to bear on improving human life and society. For more information, visit: http://seas.harvard.edu.