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Posted: Mar 30, 2011

Injectable, biodegradable gels made from gelatin nanospheres aid tissue repair

(Nanowerk Spotlight) Regenerative medicine, in particular the area of tissue regeneration, is seeing a rapidly growing field of novel biomaterials that can act as bioactive scaffolds that induce tissue regeneration; that is in contrast to the more traditional concept of passively accepted implant materials.
"In order to present biological stimuli to the physiological environment and trigger tissue repair, optimal integration of synthetic biomaterials within the surrounding tissue is of paramount importance," Huanan Wang, a PhD student in the Department of Biomaterials at Radboud University Nijmegen Medical Center in The Netherlands, explains to Nanowerk. "In that respect, hydrogels made from biodegradable polymers are ideal candidates since they are generally biocompatible, biodegradable, and, in some cases, injectable."
Wang says that colloidal gels made by a bottom-up approach using particulate building blocks are very interesting to researchers since they are injectable and exhibit improved material performance compared to traditional monolithic scaffolds for tissue regeneration. To this end, the attractive forces between the building blocks are critical to establish cohesive gels that maintain their integrity upon implantation into the human body.
Previously, colloidal gels have been developed based on micro- or nanospheres made of polymers that were functionalized with additional charged groups to increase their mutual attraction. These polymers lacked naturally occurring cell-adhesif motifs and were often cytotoxic due to the high charge density.
New research by a joint team from Radboud University and Sichuan University in China, led by Sander Leeuwenburgh, has provided firm evidence for a feasible bottom-up approach for the preparation of injectable gels by employing oppositely charged gelatin nanospheres as building blocks.
Gelatin is a well-known biopolymer with excellent biocompatibility and biodegradability while the release of drugs from gelatin can be controlled to a large extent.
Reporting their findings in the March 10, 2011, online edition of Advanced Materials ("Oppositely Charged Gelatin Nanospheres as Building Blocks for Injectable and Biodegradable Gels"), the team demonstrate that, upon mixing oppositely charged gelatin nanospheres, it is possible to form injectable and biodegradable colloidal gels.
Injectable and biodegradable gels have been formed by a bottom-up synthesis strategy employing oppositely charged gelatin nanospheres as particulate building blocks. These gels are formed by electrostatic interactions between and tight packing of gelatin nanospheres of opposite charge. (Reprinted with permission from Wiley-VCH Verlag)
"We have used gelatin since both positively and negatively charged gelatin is commercially available without the need to chemically modify these biopolymers" says Wang. "Moreover, gelatin possesses cell-recognition sites since it is derived from collagen, the main organic substance in bone."
Mixing gelatin microspheres did not yield colloidal gels, but by mixing gelatin nanoparticles of opposite charge, cohesive gels were obtained that were elastic, injectable and cohesive (even at high ionic strengths).
The main benefit of this bottom-up approach towards formation of injectable gels relates to the fact that the particulate building blocks can be functionalized by design. For instance, the degradability and corresponding drug release behavior of encapsulated biomolecules can be tailored-made.
In addition, the researchers have shown for the first time, using dynamic light scattering, that these colloidal gels are formed due to attractive electrostatic forces that cause the aggregation of the nanoparticles and the formation of a gel.
What this research shows is that elastic colloidal gels can now be made from commercially available biopolymers without additional chemical modification that might reduce their biocompatibility. This means that gelatin gels can now be loaded with drugs and other bioactive components such as biominerals, while the gels can be applied using minimally invasive surgery which is not possible using conventional, pre-made gelatin gels.
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