Nanotechnology cell carriers for knee repair

(Nanowerk Spotlight) Damaged articular cartilages, like the ones found in the knee joint, ordinarily demonstrate a very limited capability for self-healing. Functional restoration of diseased or damaged articular cartilage is a major clinical challenge. There have been a number of successful approaches to tissue engineered cartilage, including the use of natural and synthetic biomaterial scaffolds, allogeneic and autologous sources of mature chondrocytes, and chondroinductive growth factors. Although recent progress has been made in engineering cartilage of various shapes and sizes for cosmetic purposes, current treatments for cartilage repair are less than satisfactory, and rarely restore full function or return the tissue to its native state.
Researchers have now developed nanofibrous hollow microspheres self-assembled from star-shaped biodegradable polymers as an injectable cell carrier. When the spheres are injected with cells into wounds, these spheres biodegrade, but the cells live on to form new tissue.
"Developing these nanofiber spheres as cell carriers that simulate the natural growing environment of the cell is a very significant advance in tissue repair," says Peter Ma, professor at the University of Michigan School of Dentistry and lead author of a paper in the April 17, 2011 online edition of Nature Materials ("Nanofibrous hollow microspheres self-assembled from star-shaped polymers as injectable cell carriers for knee repair").
A schematic of star-shaped polymers synthesis and nanofibrous hollow microsphere fabrication
A schematic of star-shaped polymers (SS-PLLA) synthesis and nanofibrous hollow microsphere fabrication. a) PAMAM (G2) as an initiator for the synthesis of SS-PLLA. The colors show the successive PAMAM generations. b) The SS-PLLA synthesized. Red coils represent the PLLA chains. Note that some hydroxyl groups on the PAMAM surface did not react with L-lactide. c) Preparation of SS-PLLA microspheres using a surfactant-free emulsification process. d) Nanofibrous hollow microspheres were obtained after phase separation, solvent extraction and freeze-drying. (Reprinted with permission from Nature Publishing Group)
"We formed a hypothesis that the extracellular matrix-mimicking nanofibrous architecture advantageously enhances cellmaterial interactions" explains Ma. "Channels/pores at multiple scales – between spheres, within spheres and between nanofibers – promote cell migration, proliferation and mass trans- port conditions, facilitating tissue regeneration and integration with the host."
The extracellular matrix (ECM) is a natural web of nanoscale structures and has an important role in the maintenance of cell and tissue structure and function. The researchers point out that, as an artificial ECM, a good scaffolding material should mimic the advantageous features of the natural ECM.
Ma says the nanofibrous microspheres are highly porous, which allows nutrients to enter easily, and they mimic the functions of cellular matrix in the body. "Additionally, the nanofibers in these hollow microspheres do not generate much degradation byproducts that could hurt the cells," he notes.
The nanofiber spheres are combined with cells and then injected into the wound. When the nanofiber spheres, which are slightly bigger than the cells they carry, degrade at the wound site, the cells they are carrying have already gotten a good start growing because the spheres provide an environment in which the cells naturally thrive.
Using several experimental models, Ma and his team evaluated these microspheres as injectable cell carriers for tissue regeneration: "We examined the nanofibrous hollow microspheres as an injectable scaffold for cartilage regeneration using three experimental models: 1) in vitro cartilage formation; 2) subcutaneous injection into nude mice for ectopic cartilage formation; and 3) rabbit osteochondral defect repair."
They found that the in vivo regenerated cartilage from nanofibrous hollow microspheres was closest to the native cartilage in histological appearance. During testing, the nanofiber repair group grew as much as three to four times more tissue than the control group.
"The outcome differences between nanofibrous carriers and solid-interior microspheres could be partially attributed to the nanofibrous architecture" says Ma. "The overall low material densities and high surface areas of the nanofibrous hollow microspheres probably enhance protein adsorption for cellscaffold interactions and facilitate mass transfer for tissue regeneration. The faster degradation rate of the nanofibrous hollow microspheres and their hollow structure probably provided additional space for the matrix accumulation, facilitating cartilage tissue formation."
The next step is to see how the new cell carrier works in larger animals and eventually in people to repair cartilage and other tissue types.
By Michael is author of three books by the Royal Society of Chemistry:
Nano-Society: Pushing the Boundaries of Technology,
Nanotechnology: The Future is Tiny, and
Nanoengineering: The Skills and Tools Making Technology Invisible
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