David J. Mooney, Ph.D.

Researchers have developed a more durable way to repair the dural membrane (dura) that lines the brain and spinal cord. The strong and highly adhesive hydrogel called Dural Tough Adhesive (DTA) solves key problems that may happen when repairing the dural membrane lining after trauma or surgery.

The dural membrane is the outermost of three meningeal layers that line the central nervous system (CNS), which includes the brain and spinal cord. Together, the meninges function as a shock absorber to protect the CNS against trauma, circulate nutrients and remove waste.

The dura also contains cerebrospinal fluid that surrounds all CNS tissues. Injury, trauma or surgery may cause the fluid to leak, which can threaten patients’ lives, neurological functions and recovery… Continue reading.

CAMBRIDGE – December 13, 2016 – David Mooney, the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School for Engineering and Applied Sciences (SEAS) and a Core Faculty Member at the Wyss Institute for Biologically Inspired Engineering at Harvard, has been elected a Fellow of the National Academy of Inventors (NAI).  
Mooney is recognized by the NAI for having demonstrated “a highly prolific spirit of innovation in creating or facilitating outstanding inventions that have made a tangible impact on the quality of life, economic development, and the welfare of society.”
Mooney has authored more than 350 scientific papers and is an inventor on more than 28 issued U.S. patents.
“I am honored to be elected to an institution that celebrates American ingenuity and the translation of discoveries to practical use, and this is really a testimony to the brilliant students, fellows and co-workers with whom I’ve been able to work and invent over the years,” said Mooney.
Mooney has developed numerous technologies advancing tissue engineering, immunotherapy, and mechanotherapy. Most recently he and his team have developed a microfluidic-based method for encapsulating single cells within hydrogels, which could improve stem cell-based therapies and even enable precision tissue engineering using cell-by-cell construction. He has also recently developed a method for predicting how a tumor tissue’s physical properties affect the efficacy of chemotherapy drugs and also demonstrated that direct physical stimulation of injured skeletal muscles impacts biological processes and improves muscle regeneration.

Muscle regeneration through mechanical stimulation may one day replace or enhance drug- and cell-based regenerative treatments, according to a new study by a team of engineers and biomedical scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

The study suggests that mechanically driven therapies that promote skeletal muscle regeneration could augment or replace methods currently being used. The finding was published Monday in the journal Proceedings of the National Academy of Sciences.

“Chemistry tends to dominate the way we think about medicine, but it has become clear that physical and mechanical factors play very critical roles in regulating biology,” said Harvard bioengineer David Mooney, the study’s senior author. “The results of our new study demonstrate how direct physical and mechanical intervention can impact biological processes and can potentially be exploited to improve clinical outcomes.” Mooney is a Wyss Institute core faculty member and the Robert P. Pinkas Family Professor of Bioengineering at SEAS.

Researchers at the Harvard John A. Paulson School of Engineering and Applied Sciences and The Wyss Institute for Biologically Inspired Engineering have developed a new, more precise way to control the differentiation of stem cells into bone cells. This new technique has promising applications in the realm of bone regeneration, growth and healing. The research led by David Mooney, the Robert P. Pinkas Family Professor of Bioengineering at SEAS, was published in Nature Materials.

A cell’s microenvironment, the network of proteins and polymers that surrounds and connects cells within tissues, impacts a range of cellular behaviors, including stem cell differentiation. For about a decade, researchers have been able to direct the fate of stem cells by tuning the stiffness of its microenvironment, also known as the extracellular matrix. The problem with only tuning stiffness is that it assumes the environment behaves like an elastic material, like rubber. When a strain or deformation is exerted on an elastic material, elastic energy is stored and when the deformation is released, the material bounces back to its original shape like a rubber band. 

Possible stem cell therapies often are limited by low survival of transplanted stem cells and the lack of precise control over their differentiation into the cell types needed to repair or replace injured tissues. A team led by David Mooney, a core faculty member at Harvard’s Wyss Institute, has now developed a strategy that has experimentally improved bone repair by boosting the survival rate of transplanted stem cells and influencing their cell differentiation. The method embeds stem cells into porous, transplantable hydrogels.

In addition to Mooney, the team included Georg Duda, a Wyss associate faculty member and director of the Julius Wolff Institute for Biomechanics and Musculoskeletal Regeneration at Charité – Universitätsmedizin in Berlin, and Wyss Institute founding director Donald Ingber. The team published its findings in today’s issue of Nature Materials. Mooney is also the Robert P. Pinkas Family Professor of Bioengineering at the Harvard John A. Paulson School of Engineering and Applied Sciences.

Stem cell therapies have potential for repairing many tissues and bones, or even for replacing organs. Tissue-specific stem cells can now be generated in the laboratory. However, no matter how well they grow in the lab, stem cells must survive and function properly after transplantation. Getting them to do so has been a major challenge for researchers.

By isolating mechanical and biological variables one by one in vitro, a team of researchers led by Prof. David Mooney, identified a possible mechanism by which normal cells turn malignant in mammary epithelial tissues, the tissues frequently involved in breast cancer.After two years of effort, researchers led by Prof. Donhee Ham successfully measured the collective mass of ‘massless’ electrons in motion in graphene. Graphene is a one-atom-thick carbon sheet that has taken the world of physics by storm, in part because its electrons behave as massless particles. The research could provide a basis for the creation of miniaturized circuits with tiny, graphene-based components.Greg Morrisett was among five members of the Harvard faculty who were appointed Harvard College Professors, recognizing excellence in undergraduate teaching.Translucent hexagonal honeycomb printed using the baseline epoxy ink with carbon fibers added for visualization. Image courtesy of Brett G. Compton, Harvard University.Led by Prof. David Mooney, a research team loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release “on demand” drug bursts. The technique provides an innovative way to noninvasively administer drugs with a far greater level of control than was possible before. Harvard engineers led by Prof. Jennifer Lewis used new resin inks and 3D printing to develop cellular composite materials of unprecedented light weight and stiffness. Because of their mechanical properties and the fine-scale control of fabrication, these new materials mimic and improve on balsa, and even the best commercial 3D-printed polymers and polymer composites available.

The Gary Michelson Found Animals Foundation has awarded Harvard bioengineer David Mooney a three-year grant totaling more than $700,000 to pursue development of a vaccine technology that would provide a nonsurgical method for spaying and neutering dogs and cats.

Mooney is the Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS) and a Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard University.

Mooney’s team will use the grant award to adapt its existing work in implantable and injectable vaccines that activate the body’s immune system to attack cancer or infectious disease. This time, the team hopes to tune the technology towards targeting and disrupting a hormone crucial to reproduction in mammals.

Gonadotropin-releasing hormone (GnRH), which is produced in the brain, regulates the release of hormones from the pituitary gland that control reproduction in both male and female animals. Mooney and his team will explore how their various vaccine immunotherapies, which work by recruiting and activating the body’s immune cells to attack specific agents, could be used to target GnRH and produce antibodies against it, halting the reproductive process.
“As a pet owner myself, I’m excited to receive this grant award to help develop technology that could provide nonsurgical spay and neutering methods for dogs and cats,” Mooney said. “An accessible and affordable way to sterilize pets would reduce the number of animals in shelters and prevent a vast number of euthanizations.”

Current drug delivery systems used to administer chemotherapy to cancer patients typically release a constant dose of the drug over time—but a new study challenges this “slow and steady” approach and offers a novel way to locally deliver the drugs “on demand,” as reported in the Proceedings of the National Academy of Sciences (PNAS).
Led by David J. Mooney, the Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS) and a Core Faculty member at Harvard’s Wyss Institute for Biologically Inspired Engineering, the research team loaded a biocompatible hydrogel with a chemotherapy drug and used ultrasound to trigger the gel to release the drug. Like many other injectable gels that have been used for drug delivery for decades, this one gradually releases a low level of the drug by diffusion over time. To temporarily increase doses of drug, scientists had previously applied ultrasound, but that approach was a one-shot deal as the ultrasound was used to destroy those gels.
This gel was different.
The team used ultrasound to temporarily disrupt the gel such that it released short, high-dose bursts of the drug—akin to opening up a floodgate. But when they stopped the ultrasound, the hydrogels self-healed. By closing back up, the gels were ready to go for the next “on demand” drug burst, providing an innovative way to administer drugs with a far greater level of control than was possible before.
That’s not all. The team also demonstrated—in lab cultures and in mice with breast cancer tumors—that the pulsed, ultrasound-triggered hydrogel approach to drug delivery was more effective at stopping the growth of tumor cells than traditional, sustained-release drug therapy.
“Our approach counters the current paradigm of sustained drug release and offers a double whammy,” said Mooney. “We have shown that we can use the hydrogels repeatedly and turn the drug pulses on and off at will, and that the drug bursts in concert with the baseline low-level drug delivery seem to be particularly effective in killing cancer cells.”

A team of researchers led by David J. Mooney, the Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS), has identified a possible mechanism by which normal cells turn malignant in mammary epithelial tissues, which are frequently involved in breast cancer.

Dense mammary tissue has long been recognized as a strong indicator of risk for breast cancer. This is why regular breast examinations are considered essential to early detection. Until now, however, the significance of that tissue density has been poorly understood.

By isolating mechanical and biological variables one by one in vitro, Mooney and his research team discovered how the physical forces and chemical environment in those dense tissues can drive cells into a dangerously invasive, proliferating mode. The findings were published online in Nature Materials.

“While genetic mutations are at the root of cancer, a number of studies over the last 10 to 20 years have implicated the cellular microenvironment as playing a key role in promoting or suppressing tumor progression,” said lead author Ovijit Chaudhuri, a former postdoctoral fellow in the Mooney Lab at Harvard who recently joined the mechanical engineering faculty at Stanford University.

The new research found that the stiffness of the extracellular matrix and the availability of certain ligands (molecules that bind to cell membranes) can together determine which genes are actually called on — and whether normal epithelial cells begin to exhibit the behaviors characteristic of highly malignant cancer cells.

A Harvard-led team is the first to demonstrate the ability to use low-power light to trigger stem cells inside the body to regenerate tissue, an advance they reported in Science Translational Medicine. The research, led by Wyss Institute Core Faculty member David Mooney, Ph.D., lays the foundation for a host of clinical applications in restorative dentistry and regenerative medicine more broadly, such as wound healing, bone regeneration, and more.

The team used a low-power laser to trigger human dental stem cells to form dentin, the hard tissue that is similar to bone and makes up the bulk of teeth. What’s more, they outlined the precise molecular mechanism involved, and demonstrated its prowess using multiple laboratory and animal models.

A number of biologically active molecules, such as regulatory proteins called growth factors, can trigger stem cells to differentiate into different cell types. Current regeneration efforts require scientists to isolate stem cells from the body, manipulate them in a laboratory, and return them to the body—efforts that face a host of regulatory and technical hurdles to their clinical translation. But Mooney’s approach is different and, he hopes, easier to get into the hands of practicing clinicians.

David Mooney, Ph.D., a Core Faculty member at the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences, has been elected to the Institute of Medicine (IOM) of the National Academies, which is one of the highest honors in the field of medicine in the United States.

The IOM is an organization with more than 1,900 members and foreign associates that recognizes individuals who have made seminal contributions to medicine, healthcare, and public health. Its members serve on committees and boards that advise government agencies, policy makers, and professionals on healthcare issues. Mooney joins 70 new members and ten foreign associates elected this year.

Mooney is being honored for his pioneering work in the tissue-engineering field, and his substantial contributions to the fields of biomaterials, drug delivery, and mechanotransduction. In addition, his recent work in therapeutic cancer vaccines could transform the treatment of cancer. Mooney leads the Programmable Nanomaterials Platform at the Wyss Institute. Scientists in that platform create therapeutic biomaterials that seek out injury sites, deliver drugs, and promote tissue repair.

"I’m deeply honored to be elected to this illustrious organization and join such an extraordinary group of medical scientists and physicians," Mooney said.

Cross-disciplinary team from Harvard University and Dana-Farber Cancer Institute brings novel therapeutic cancer vaccine to human clinical trials

A cross-disciplinary team of scientists, engineers, and clinicians announced today that they have begun a Phase I clinical trial of an implantable vaccine to treat melanoma, the most lethal form of skin cancer.

The effort is the fruit of a new model of translational research being pursued at Harvard University that integrates the latest cancer research with bioinspired technology development. It was led by David J. Mooney, who is the Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS) and a Core Faculty Member at the Wyss Institute for Biologically Inspired Engineering at Harvard, along with Glenn Dranoff, who is co-leader of Dana-Farber Cancer Institute’s Cancer Vaccine Center, a professor at Harvard Medical School, and an associate faculty member at the Wyss Institute.

Most therapeutic cancer vaccines available today require doctors to first remove the patient’s immune cells from the body, then reprogram them and reintroduce them back into the body. The new approach, which was first reported to eliminate tumors in mice in Science Translational Medicine in 2009, instead uses a small disk-like sponge about the size of a fingernail that is made from FDA-approved polymers. The sponge is implanted under the skin, and is designed to recruit and reprogram a patient’s own immune cells “on site,” instructing them to travel through the body, home in on cancer cells, then kill them.

Compressible bioscaffold pops back to its molded shape once inside the body

Bioengineers at Harvard have developed a gel-based sponge that can be molded to any shape, loaded with drugs or stem cells, compressed to a fraction of its size, and delivered via injection. Once inside the body, it pops back to its original shape and gradually releases its cargo, before safely degrading.

The biocompatible technology, revealed this week in the Proceedings of the National Academy of Sciences, amounts to a prefabricated healing kit for a range of minimally invasive therapeutic applications, including regenerative medicine.

"What we’ve created is a three-dimensional structure that you could use to influence the cells in the tissue surrounding it and perhaps promote tissue formation," explains principal investigator David J. Mooney, Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS) and a Core Faculty Member at the Wyss Institute for Biologically Inspired Engineering at Harvard.

Honor From The Tissue Engineering International & Regenerative Medicine Society-North America Recognizes His Significant Contributions

On behalf of the Tissue Engineering International & Regenerative Medicine Society-North America (TERMIS-NA), Harvard’s David Mooney has been awarded the Senior Scientist Award.

Mooney is the Robert P. Pinkas Family Professor of Bioengineering at the Harvard School of Engineering and Applied Sciences (SEAS) and a Core FacultyMember at the Wyss Institute for Biologically Inspired Engineering at Harvard.

Mooney, who earned his Ph.D. in Chemical Engineering at the Massachusetts Institute of Technology and B.S. in Chemical Engineering at the University of Wisconsin, Madison, designs and synthesizes new biomaterials that regulate the gene expression of interacting cells for a variety of tissue engineering and drug delivery projects.

Current projects conducted in his lab focus on therapeutic angiogenesis, regeneration of musculoskeletal tissues, and cancer therapies.

A cancer vaccine carried into the body on a carefully engineered, fingernail-sized implant is the first to successfully eliminate tumors in mammals, a team of Harvard bioengineers and biologists report today in the journal Science Translational Medicine.

The new approach uses plastic disks impregnated with tumor-specific antigens and implanted under the skin to reprogram the mammalian immune system to attack tumors. The journal article describes the use of such implants to eradicate melanoma tumors in mice.

“This work shows the power of applying engineering approaches to immunology,” said David J. Mooney, the Robert P. Pinkas Family Professor of Bioengineering in Harvard’s School of Engineering and Applied Sciences and a member of the faculty of the Wyss Institute for Biologically Inspired Engineering. “By marrying engineering and immunology through this collaboration with Harvard Medical School associate professor Glenn Dranoff, at the Dana-Farber Cancer Institute, we’ve taken a major step toward the design of effective cancer vaccines.”