Oppositely Charged Gelatin Nanospheres as Building Blocks for Injectable and Biodegradable Gels

Abstract

biodegradable gels, since physical crosslinking based on electrostatic interactions is generally favored over the use of chemical crosslinking to achieve sustained drug release, [ 17 ] cell attachment, [ 18 ] or hydrogel formation. [ 19 ] Recently, oppositely charged dextran microspheres [ 20 ] or poly(lactic-co -glycolic acid) (PLGA) nanospheres [ 21 ] have been used to form moldable scaffolds, but only indirect proof for electrostatic self-assembly was provided based on rheological characterization, while the underlying gel formation mechanism was not elucidated. Moreover, disadvantages of these gels include: i) the necessity to derivatize dextran or PLGA by grafting charged groups onto the polymer backbone, which moreover induced cytotoxicity; [20b] ii) the release of harmful degradation byproducts, such as lactic and glycolic acid (in case of PLGA nanospheres), which can denature entrapped signaling proteins [ 22 ] and cause infl ammatory responses [ 23 ] of the host tissue; and iii) the absence of cell-adhesive peptide sequences required for the attachment of anchorage-dependent mesenchymal stem cells such as fi bro-and osteoblasts. [ 17 ]

Enhanced Bone Regeneration of Cortical Segmental Bone Defects Using Porous Titanium Scaffolds Incorporated with Colloidal Gelatin Gels for Time- and Dose-Controlled Delivery of Dual Growth Factors

“…17 Briefly, gelatin nanospheres were obtained using a desolvation method and crosslinked using GA. A crosslinking density (defined as molar ratios of GA relative to [NH 2 ] gelatin ) of one (low) or four (high) was applied to GelA and GelB nanospheres, respectively. That resulted in positively charged GelA and negatively charged GelB nanospheres.…”

The Use of Micro- and Nanospheres as Functional Components for Bone Tissue Regeneration

“…Nanosphere-based colloidal systems generally display superior properties (i.e., higher stability and better injectability/moldability) compared with microsphere-based systems owing to higher interparticle forces. 52,87,125,126 Still, nanospheres also display several drawbacks compared with microspheres that are related to (i) lack of costeffective preparation techniques for nanospheres which allow for easy upscaling without using harsh processing conditions, (ii) reduced stability under in vitro and in vivo conditions due to their intrinsic high surface area that maximizes interaction with the physiological environment, (iii) the tendency of nanospheres to aggregate into a microscale that mitigates potential benefits of the use of nanoscale particles, and, finally, (iv) unsuitability for various applications in bone tissue engineering that require micron-scale particles such as the creation of macroporosity and delivery of cells.…”

“…[49][50][51] Interestingly, injectable colloidal gels using gelatin nanospheres as building blocks have been recently developed in our group that are characterized by high elasticity, excellent handling properties, ease of functionalization, and cost effectiveness, which shows a great potential for tissue engineering (see Directed assembly section). 52 Despite the favorable properties, critical concerns of gelatin are related to its potential to induce immunogenic responses and the poor control on its physicochemical behavior due to the animal origin. To overcome these drawbacks, microspheres made of recombinant gelatin with well-defined and tunable molecular weights, amino acid sequences (such as RGD peptides), and isoelectric points have been recently developed by using emulsion methods.…”

“…162 To overcome these disadvantages, oppositely charged gelatin nanospheres have been developed by using commercially available cationic and anionic gelatin, which facilitated the fabrication of gelatin micro-/nanospheres with positive and negative charges without the necessity of additional functionalization. 52 As a result, the combination of oppositely charged gelatin nanospheres gave rise to injectable and biodegradable colloidal gels with high elasticity at low nanosphere concentrations owing to electrostatic selfassembly between and tight packing of gelatin nanospheres (Fig. 5).…”

Stimulus-Responsive Heteroaggregation of Colloidal Dispersions: Reversible Systems and Composite Materials

“…In tissue engineering gels are used as a supporting matrix for the delivery of cells. Gelatin nanospheres have been used to form biodegradable colloidal gels by mixing oppositely charged nanospheres under physiological conditions [43]. Elastic gels were formed at low solid content as a result of electrostatic self-assembly between the nanospheres as well as additional stabilization of the gels caused by intimate contact between the nanospheres owing to the deformable nature of the particles.…”