Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:


Microneedling therapeutic stem cells into damaged tissues


Small and minimally invasive 'Detachable Microneedle Depots' effectively deliver stem cells for localized MSC therapy of skin disorders

Mesenchymal stem cells (MSCs) are multipotent in that they naturally replenish the cell types that build our bone, cartilage and adipose tissues.

Microneedles, made of a biomaterial mixed with therapeutic agents, are attached to a strip of tape, needles facing down. The strip is applied to the wound area of the skin and the tape removed. The needles are embedded into the skin and degrade, delivering the therapeutic agent under the skin.

Credit: Khademhosseini Lab

However, their much broader regenerative potential, based on their capacity to migrate and engraft in injured tissues and secrete factors that enhance the formation of new blood vessels, suppress inflammation and cell death, and promote healing, makes them exquisite candidates for cell-based therapies for diseases as varied as cardiovascular, liver, bone and cartilage diseases, lung and spinal cord injuries, autoimmune diseases and even cancer and skin lesions.

MSCs provoke no or negligible adverse reactions in patients that receive them from healthy donors, and can be easily isolated from human tissues, expanded to clinical scales, biopreserved, and stored for point-of-care delivery.

This efficiency in preparing medical grade MSCs contrasts with the relative inefficiency with which they currently can be delivered to target tissues in patients. Clinicians often need to administer massive numbers of MSCs with high precision to reach sufficient numbers of cells that successfully engraft and remain functional over time.

To overcome this bottleneck, researchers have developed materials-based approaches in which MSCs are embedded in biomaterial scaffolds that then can be implanted as "patches" in minimally invasive procedures into damaged tissues. However, those cells are often limited in their ability to migrate, overcome tissue barriers, and successfully engraft in tissue microenvironments where their action is needed most.

In principle, injection approaches can introduce MSCs into tissues via hypodermic needles in a more targeted manner, but any direct injection to the tissue is invasive and can cause inadvertent tissue damage and side effects like the formation of scar tissue.

Now, a new study reported in Advanced Functional Materials by a team at the Terasaki Institute for Biomedical Innovation in Los Angeles and the University of California, Los Angeles (UCLA) has developed a minimally invasive approach, which deploys "microneedles" that provide a bioactive depot of MSCs.

By embedding comparatively low numbers of MSCs in a gel-like material that prolongs their viability and functionality, and targeting damaged tissues with high spatial precision, the researchers showed their approach to accelerate wound healing in a mouse model with excised skin segments.

"Microneedles have been successfully used in the past to painlessly deliver drugs to target tissues such as skin, blood vessels and eyes. We demonstrate here with 'Detachable Microneedle Depots' that an analogous approach can deploy therapeutic cells at target sites," said co-corresponding author Ali Khademhosseini, the Director and CEO of the Terasaki Institute who was previously Director of the UCLA Center for Minimally Invasive Therapeutics.

"To achieve this, we developed an entirely new microneedle patch that supports stem cells' viability, responsiveness to wound stimuli, and ability to accelerate wound healing."

At the beginning of their study, Khademhosseini and his co-workers hypothesized that embedding MSCs in a biocompatible and biodegradable biomaterial matrix could help create a hydrated environment with the mechanical properties that stem cells need in order to remain alive and functioning over a longer time.

The researchers started by engineering a matrix of gelatin fibers that are cross-linked to each other into a network that could accommodate MSCs. The biomaterial mimicked the normal extracellular environment of tissues that MSCs normally reside in, and it helped to remodel the specific matrix environment in a way that allowed MSCs to take up nutrients and communicate with damaged tissue via soluble factors that they normally receive and dispatch.

The other part of the challenge was to introduce the literal "needle" quality into the cell-delivering device that would enable it to gently penetrate tissues in order to reach their target sites. To this aim, the researcher encased the softer MSC-containing gelatin matrix with a second, much harder biomaterial known as poly(lactic-co-glycolic)acid, in short PLGA.

Once the needles were brought into place in a wound bed, the "PLGA shell", which also is biocompatible and biodegradable, slowly degraded, but during the process kept the MSC-containing gelatin matrix in place, allowing MSCs to release their therapeutic factors through emerging gaps in the shell into the damaged tissue. The team showed that in the composite microneedle 90% of MSCs were kept viable for 24 hours, and that, importantly the cells did not lose their potential as stem cells ("stemness"), which was critical for their healing properties.

Finally, the team set out to investigate their microneedle concept in a mouse skin wound model in which a defined excision is made in the epidermal tissue layers. To be able to strategically place individual microneedles within the wound bed, a simple and effective deployment mechanism was devised by attaching an array of microneedles on a small strip of scotch tape with their pointy ends facing away from the tape.

Precisely positioning the tape with its patterned microneedle surface on the wound, allowed the individual microneedles to penetrate into the wound bed. Then, the tape was peeled off, causing the microneedles to detach and remain embedded in the wound tissue. Khademhosseini and his co-workers summarized the device's salient features by naming it: "Detachable Hybrid Microneedle Depot" (d-HMND).

In the mouse model, the MSC-loaded d-HMND device indeed stimulated a number of critical parameters associated with wound healing. Compared to an equal number of MSCs injected directly into wounded skin, and a version of the d-HMND device that did not contain any MSCs (cell-free), the MSC-containing d-HMND accelerated the contraction of the wound and re-growth of the epidermal skin layers (re-epithelialization).

The researchers used a panel of histological and molecular markers to confirm over a period of 14 days that the device suppressed inflammation, and stimulated tissue remodeling, the formation of new blood vessels, and re-growth of hair - all vital signs of a robust wound healing response.

"In future scenarios, d-HMNDs could be rapidly fabricated in clinical laboratories shortly before use, applied to treat skin injuries, and explored more broadly as treatments for a variety of other disorders, including melanoma and other dermatological disorders that could benefit from the power of MSC cells," said Khademhosseini. "The concept would even be compatible with using patient-derived cells in more personalized device approaches." Khademhosseini and his colleagues are exploring further uses of this technology as part of the Terasaki Institute's research program.


The study also included co-first authors KangJu Lee, Ph.D., who co-corresponded the work with Khademhosseini, and Yumeng Xue; as well as Junmin Lee, Ph.D., Han-Jun Kim, DVM/Ph.D., Yaowen Liu, Peyton Tebon, Einollah Sarikhani, Wujin Sun, Ph.D., Shiming Zhang, Ph.D., Reihaneh Haghniaz, Ph.D., Betül Çelebi-Saltik, Ph.D., Xingwu Zhou, Serge Ostrovidov, Ph.D., Samad Ahadian, Ph.D., Nureddin Ashammakhi, M.D., Ph.D., and Mehmet Dokmeci, Ph.D. It was funded by the National Institutes of Health under grants EB021857, AR066193, AR057837, CA214411, HL137193, EB024403, EB023052, and EB022403.


Terasaki Institute for Biomedical Innovation

Stewart Han,, +1 818-836-4393

The Terasaki Institute for Biomedical Innovation ( is a non-profit research organization that invents and fosters practical solutions that restore or enhance the health of individuals. Research at the Terasaki Institute leverages scientific advancements that enable an understanding of what makes each person unique, from human tissues down to genes, to create technological solutions for some of the most pressing medical problems of our time. We use innovative technology platforms to study human disease on the level of individual patients by incorporating advanced computational and tissue-engineering methods. Findings yielded by these studies are translated by our research teams into tailored diagnostic and therapeutic approaches encompassing personalized materials, cells and implants with unique potential and broad applicability to a variety of diseases, disorders and injuries.

The Institute is made possible through an endowment from the late Dr. Paul I. Terasaki, a pioneer in the field of organ transplant technology.

Media Contact

Stewart Han


Stewart Han | EurekAlert!
Further information:

More articles from Life Sciences:

nachricht Rising water temperatures could endanger the mating of many fish species
03.07.2020 | Alfred-Wegener-Institut, Helmholtz-Zentrum für Polar- und Meeresforschung

nachricht Moss protein corrects genetic defects of other plants
03.07.2020 | Rheinische Friedrich-Wilhelms-Universität Bonn

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Electrons in the fast lane

Solar cells based on perovskite compounds could soon make electricity generation from sunlight even more efficient and cheaper. The laboratory efficiency of these perovskite solar cells already exceeds that of the well-known silicon solar cells. An international team led by Stefan Weber from the Max Planck Institute for Polymer Research (MPI-P) in Mainz has found microscopic structures in perovskite crystals that can guide the charge transport in the solar cell. Clever alignment of these "electron highways" could make perovskite solar cells even more powerful.

Solar cells convert sunlight into electricity. During this process, the electrons of the material inside the cell absorb the energy of the light....

Im Focus: The lightest electromagnetic shielding material in the world

Empa researchers have succeeded in applying aerogels to microelectronics: Aerogels based on cellulose nanofibers can effectively shield electromagnetic radiation over a wide frequency range – and they are unrivalled in terms of weight.

Electric motors and electronic devices generate electromagnetic fields that sometimes have to be shielded in order not to affect neighboring electronic...

Im Focus: Gentle wall contact – the right scenario for a fusion power plant

Quasi-continuous power exhaust developed as a wall-friendly method on ASDEX Upgrade

A promising operating mode for the plasma of a future power plant has been developed at the ASDEX Upgrade fusion device at Max Planck Institute for Plasma...

Im Focus: ILA Goes Digital – Automation & Production Technology for Adaptable Aircraft Production

Live event – July 1, 2020 - 11:00 to 11:45 (CET)
"Automation in Aerospace Industry @ Fraunhofer IFAM"

The Fraunhofer Institute for Manufacturing Technology and Advanced Materials IFAM l Stade is presenting its forward-looking R&D portfolio for the first time at...

Im Focus: AI monitoring of laser welding processes - X-ray vision and eavesdropping ensure quality

With an X-ray experiment at the European Synchrotron ESRF in Grenoble (France), Empa researchers were able to demonstrate how well their real-time acoustic monitoring of laser weld seams works. With almost 90 percent reliability, they detected the formation of unwanted pores that impair the quality of weld seams. Thanks to a special evaluation method based on artificial intelligence (AI), the detection process is completed in just 70 milliseconds.

Laser welding is a process suitable for joining metals and thermoplastics. It has become particularly well established in highly automated production, for...

All Focus news of the innovation-report >>>



Industry & Economy
Event News

International conference QuApps shows status quo of quantum technology

02.07.2020 | Event News

Dresden Nexus Conference 2020: Same Time, Virtual Format, Registration Opened

19.05.2020 | Event News

Aachen Machine Tool Colloquium AWK'21 will take place on June 10 and 11, 2021

07.04.2020 | Event News

Latest News

Rising water temperatures could endanger the mating of many fish species

03.07.2020 | Life Sciences

Risk of infection with COVID-19 from singing: First results of aerosol study with the Bavarian Radio Chorus

03.07.2020 | Studies and Analyses

Efficient, Economical and Aesthetic: Researchers Build Electrodes from Leaves

03.07.2020 | Power and Electrical Engineering

Science & Research
Overview of more VideoLinks >>>