Nature Materials - To repair complexly shaped tissue defects, an injectable cell carrier is desirable to achieve an accurate fit and to minimize surgical intervention. However, the injectable carriers available at present have limitations, and are not used clinically for cartilage regeneration. Here, we report nanofibrous hollow microspheres self-assembled from star-shaped biodegradable polymers as an injectable cell carrier. The nanofibrous hollow microspheres, integrating the extracellular-matrix-mimicking architecture with a highly porous injectable form, were shown to efficiently accommodate cells and enhance cartilage regeneration, compared with control microspheres. The nanofibrous hollow microspheres also supported a significantly larger amount of, and higher-quality, cartilage regeneration than the chondrocytes-alone group in an ectopic implantation model. In a critical-size rabbit osteochondral defect-repair model, the nanofibrous hollow microspheres/chondrocytes group achieved substantially better cartilage repair than the chondrocytes-alone group that simulates the clinically available autologous chondrocyte implantation procedure. These results indicate that the nanofibrous hollow microspheres are an excellent injectable cell carrier for cartilage regeneration.
Repairing tissue is very difficult and success is extremely limited by a shortage of donor tissue, says Ma, who also has an appointment at the U-M College of Engineering. The procedure gives hope to people with certain types of cartilage injuries for which there aren't good treatments now. It also provides a better alternative to ACI, which is a clinical method of treating cartilage injuries where the patient's own cells are directly injected into the patient's body. The quality of the tissue repair by the ACI technique isn't good because the cells are injected loosely and are not supported by a carrier that simulates the natural environment for the cells, Ma says.
To repair complex or oddly shaped tissue defects, an injectable cell carrier is desirable to achieve accurate fit and to minimize surgery, he says. Ma's lab has been working on a biomimetic strategy to design a cell matrix—a system that copies biology and supports the cells as they grow and form tissue—using biodegradable nanofibers.
Ma says the nanofibrous hollow 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 says.
The nanofibrous hollow 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 nanofiber spheres provide an environment in which the cells naturally thrive.
This approach has been more successful than the traditional cell matrix currently used in tissue growth, he says. Until now, there has been no way to make such a matrix injectable so it's not been used to deliver cells to complex-shaped wounds.
During testing, the nanofiber repair group grew as much as three to four times more tissue than the control group, Ma says. 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.
polymer concentration. SEM images of nanofibrous hollow microspheres prepared from
SS-PLLA with varying concentrations: (A) 1.0% (wt/v); (B) 6.0% (wt/v).
32 pages of supplemental material
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