RegenMed and stem cell gadgets review – 2012 part II

by Alexey Bersenev on August 31, 2012 · 0 comments

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Last year we introduced the term “regenmed gadget“. Since that we reviewed a variety of gadgets and new smart technologies. This is the 5th issue of our “gadgets review”.

1. The first prototype of cyborg tissue
Cyborg tissue is a hybrid of the cells and nanoscale electronics. The first prototype was recently created by Harvard-MIT researchers and published in Nature Materials. One would ask: “What is the point?” Well, drug screen, implantable prosthetics, engineering of excitable tissues (muscle, neural) – far not the complete list of potential applications:

Lieber says numerous pharmaceutical companies have already expressed interest in the scaffolds to monitor drug responses in different tissues. “That’s the nearest-term application,” he says—but not the ultimate goal. Someday, Lieber would like to develop tissue grafts that can report their function to doctors and provide immediate feedback to a tissue when necessary, such as releasing a drug into the skin or lungs. “We have the opportunity to merge electronics with cellular systems,” he says.

We will watch with a great interest the future development of this technology.

2. New biosutures
Biosutures is a new generation of smart surgical threads, with embedded cells, growth factors of biosensors. I’d like to bring your attention to the latest 3 types of biosutures.

(A) Coated with bone marrow mesenchymal stromal cells
There are few approaches, developed by different research groups, for embedding the mesenchymal stromal cells (MSC) into sutures. Standford’s group used suture pre-coated with cell adhesion molecule 1 for seeding of rat bone marrow-derived MSC. The tasted the advantage of biosuture with MSC in tendon repair model.

Yet another group have tested how pre-cating suture with proteins will affect MSC persistence and performance:

… coating absorbable sutures with proteins, especially serum albumin, improves attachment and proliferation of cells, and only 48 hours in culture is enough to cover the sutures sufficiently.
Long-term results at 5 weeks showed that transplanted cells survived and the sutures were partly absorbed
Using these stitches in vivo resulted in short-term and long-term survival of cells. As a result, albumin-coated suture can be a vehicle for stem cell therapy in soft tissues such as muscle, tendon, or peripheral nerves.

(B) Coated with adipose-derived stem cells
Spanish research group tested biosutures with adipose-derived stem cells in the mouse model of tracheal anastomosis:

Biosutures are a comfortable way of stem cell delivery to the surgical field without modification of the operative protocol. ASCs suppress the local acute inflammatory reaction (increased macrophage migration and decreased neutrophil infiltration) in the tracheal anastomosis and cause an early switch from acute to chronic inflammation.

(C) Temperature-sensitive biosuture
New biosuture, which able to sense a temperature change in a wound, could be applied in regenerative medicine:

The electronic sutures, which contain ultrathin silicon sensors integrated on polymer or silk strips, can be threaded through needles, and in animal tests researchers were able to lace them through skin, pull them tight, and knot them without degrading the devices.

The sutures can precisely measure temperature—elevated temperatures indicate infection—and deliver heat to a wound site, which is known to aid healing.

3. Engineered vascular niche in myocardium
One of the major problems in tissue engineering is a prolonged controlled release a growth factors in damaged tissue. If growth factors are not mobilized, they have very short half-life period. Very interesting study, which demonstrates that such prolonged growth factor release can create a “regenerative tissue niche”, was recently published in Science Translational Medicine.

… we carried out experiments to test whether intramyocardial injection of self-assembling peptide nanofibers (NFs) combined with vascular endothelial growth factor (VEGF) could create an intramyocardial microenvironment with prolonged VEGF release to improve post-infarct neovascularization in rats.

NF/VEGF injection not only allowed controlled local delivery but also transformed the injected site into a favorable microenvironment that recruited endogenous myofibroblasts and helped achieve effective revascularization. The engineered vascular niche further attracted a new population of cardiomyocyte-like cells to home to the injected sites, suggesting cardiomyocyte regeneration. Follow-up studies in pigs also revealed healing benefits consistent with observations in rats.

4. A prototype of vascular network for engineered tissue
The problem of vascularization of tissue engineered constructs could be solved by printing of artificial vascular network with following embedding it into the tissue. The prototype of such network was created by Christopher Chen’s team at The University of Pennsilvania, using RepRap printer:

With promising indications that their vascular networks will be compatible with all types of cells and gels, the team believes their 3D printing method will be a scalable solution for a wide variety of cell- and tissue-based applications because all organ vasculature follows similar architectural patterns.

“Cell biologists like the idea of 3D printing to make vascularized tissues in principle, but they would need to have an expert in house and highly specialized equipment to even attempt it,” Miller said. “That’s no longer the case; we’ve made these sugar-based vascular templates stable enough to ship to labs around the world.”

The study published in Nature Materials

5. A prototype of human textile for blood vessels
Cytograft has proposed a new way to create a strong non-degradable bioengineered blood vessels. They use allogeneic extracellular matrix sheets, produced by skin fibroblasts to create a “vessel” by rolling it into tubes:

The rolling process, however, is expensive and time-consuming, in part because cells must be used to fuse the tube together so that it is sturdy enough for transplantation. Slicing the sheets into thin ribbons that can be spooled into threads makes it possible to use automated weaving and braiding machines to create three-dimensional structures that do not require fusing.

“Woven textile” technique was initially developed in 2005, but new – automated version – was reported only this year.

Cytograft press-release (.pdf).

6. Stem cell microchip for neural toxicity monitoring
Korean researchers created a chip with neural stem cells, which could be used for testing of neurotoxins:

In this study, we fabricated peptide nanopatterned layer on gold electrode for increasing the affinity between the stem cell and an artificial electrode surface by self-assembly technique.
Our newly developed stem cell chip can be used as useful label-free analysis tool for detecting drug effects or for assessing the toxicity electrochemically.

7. Composite scaffold with nanoclay for controlled drug release
If we can solve a problem of growth factors short half-life in vivo, we can widely use it in regenerative medicine without necessity of cell transplantation. There are many prototypes of “smart scaffold”, which can mobilize and slowly release growth factors. The recent study, brought us closer to the possibilities of slow controlled drug release:

A rapid prototyped macroporous polycaprolactone scaffold was embedded with a porous matrix composed of chitosan, nanoclay, and β-tricalcium phosphate by freeze-drying. This composite scaffold was evaluated on its ability to deliver an anthracycline antibiotic and to promote formation of mineralized matrix in vitro.
The scaffolds comprising nanoclay released up to 45% of the drug for up to 2 months, while the scaffold without nanoclay released 95% of the drug within 4 days. Therefore, this scaffold can fulfill the requirements for both bone tissue engineering and local sustained release of an anticancer drug in vitro.

I’d imagine, that in the future we will able to control remotely release of growth factors or drugs, from implanted hydrogel. These growth factors can create a regenerative niche (see #3 above) or attract endogenous tissue-resident stem/ progenitor cells, which could heal the damage.

That’s all for this issue. Follow RegenMed and stem cell gadgets!

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