Design of Nanocomposite Injectable Hydrogels for Minimally Invasive Surgery

Abstract

CONSPECTUS: Biocompatible hydrogels are materials that hold great promise in medicine and biology since the porous structure, the ability to entrap a large amount of water, and the tunability of their mechanical and tissue adhesive properties make them suitable for several applications, including wound healing, drug and cell delivery, cancer treatment, bioelectronics, and tissue regeneration. Among the possible developed systems, injectable hydrogels, owing to their properties, are optimal candidates for in vivo minimally invasive procedures. To be injectable, a hydrogel must be liquid before and during the injection, but it must quickly jellify after injection to form a soft, self-standing, solid material. The possibility to work with a liquid precursor encoding the functions that will be available after gelation allows the development of biocompatible materials that can be employed in surgery and, in particular, in noninvasive procedures. The underlying idea is to reach the target tissue by using just a needle, or by exploiting the natural body orifices, reducing surgery procedure time, induced pain, and risk of infections. Hydrogels with different properties can be obtained by changing the type of cross-linking, the cross-linking density or the molecular weight of the polymer, or by introducing pending functional groups. The introduction of a nanofiller in the hydrogel network allows for expanding the suite of the structural and functional properties and for better mimicking native tissues. In this Account, we discuss how to provide a hydrogel network with designed properties by playing with both the polymeric chains and the fillers. We present selected examples from the literature that show how to introduce stiffness, stretchability, adhesiveness, self-healing, anisotropy, antimicrobial activity, biodegradability, and conductivity in injectable hydrogels. We further describe how the chemical composition, the mechanical properties, and the microarchitecture of the hydrogel influence cell adhesion, proliferation, and differentiation. Examples of injectable hydrogels for innovative minimally invasive procedures are then discussed in detail; in particular, we showcase the use of hydrogels for tumor resection and as vascular chemoembolization agents. We further discuss how one can improve the rheological properties of injectable hydrogels to exploit them in osteochondral tissue engineering. The effect of the introduction of a conductive filler is then presented in relation to the development of electroactive scaffolds for cardiac-tissue engineering and neural and nerve repair. We believe that the rational design of biocompatible, injectable hybrid hydrogels with tunable properties will likely play a crucial role in reducing the invasiveness and improving the outcome of several clinical and surgical setups.

<p>Nano-Silicate-Reinforced and SDF-1α-Loaded Gelatin-Methacryloyl Hydrogel for Bone Tissue Engineering</p>

“…Consistent with previous studies, 17,22,59 the composited polymer-embodied SN provided the polymer with excellent injectability. The injectability of the GelMA-SN-SDF -1α (uncrosslinked) hydrogel is primarily attributed to the shear-thinning property of SN.…”

“…[29][30][31] In particular, injectable osteogenic hydrogels have been attracting attention owing to their unique ability to fill irregular bone defects using minimally invasive procedures. [15][16][17] However, considering the complication of most synthetic processes, most fabrication strategies to date are time-consuming and expensive. [51][52][53] Although some stem cell-loaded hydrogels have demonstrated the capability to promote bone regeneration in animal models, 25,54,55 these strategies are affected by limited cell sources, low cell viability, or controversial therapeutic effects.…”

“…The injectability of the GelMA-SN-SDF -1α (uncrosslinked) hydrogel is primarily attributed to the shear-thinning property of SN. 17,60 SN is a nano diskshaped plate (25 nm in diameter, 0.92 nm in height) characterized by a positively charged surface and negatively charged edge. 61 In dry powder form, the electrostatic interactions typically result in SN crystal stacks.…”

“…In detail, the injection force was analyzed using Instron 5940 (Instron, Norwood, MA, USA). GelMA-SN hydrogel (2%) was injected from a 1-mL syringe with 1.5-inch needles of 17,19,21,23,25, and 27 G ( Figure 1D). All measurements were obtained at a flow rate of 2 mL/h.…”

“…15 Injectable osteogenic hydrogels have been attracting considerable attention because of their ability to fill irregular bone defects using a minimally invasive procedure. 16,17 However, from a clinical perspective, the fabrication of an injectable hydrogel platform involving simple and rapid production possessing long-term osteogenic ability remains highly desirable.…”