In situ spray deposition of cell‐loaded, thermally and chemically gelling hydrogel coatings for tissue regeneration

Abstract

In this study, the efficacy of creating cellular hydrogel coatings on warm tissue surfaces through the minimally invasive, sprayable delivery of thermoresponsive liquid solutions was investigated. Poly(N-isopropylacrylamide)-based (pNiPAAm) thermogelling macromers with or without addition of crosslinking polyamidoamine (PAMAM) macromers were synthesized and used to produce in situ forming thermally and chemically gelling hydrogel systems. The effect of solution and process parameters on hydrogel physical properties and morphology was evaluated and compared to poly(ethylene glycol) and injection controls. Smooth, fast, and conformal hydrogel coatings were obtained when pNiPAAm thermogelling macromers were sprayed with high PAMAM concentration at low pressure. Cellular hydrogel coatings were further fabricated by different spraying techniques: single-stream, layer-by-layer, and dual stream methods. The impact of spray technique, solution formulation, pressure, and spray solution viscosity on the viability of fibroblast and osteoblast cells encapsulated in hydrogels was elucidated. In particular, the early formation of chemically crosslinked micronetworks during bulk liquid flow was shown to significantly affect cell viability under turbulent conditions compared to injectable controls. The results demonstrated that sprayable, in situ forming hydrogels capable of delivering cell populations in a homogeneous therapeutic coating on diseased tissue surfaces offer promise as novel therapies for applications in regenerative medicine. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2383-2393, 2016.

A Review of the Fundamental Principles and Applications of Solution Blow Spinning

“…94,95 Crucial parameters such as polymer concentration, solution viscosity, and spraying technique may affect cell viability but do not prevent the simultaneous deposition of cells and material. 96 Biological materials, such as collagen and silk, merit further investigation as a material source for SBS given their outstanding mechanical properties, particularly if they can be spun in their native folded state and then used to fabricate low-cost biomimetic materials. 97 A number of biological materials have been spun into fibers by SBS, including soy protein, fish sarcoplasmic protein, and cellulose acetate (Table 2).…”

A versatile three-dimensional foam fabrication strategy for soft and hard tissue engineering

“…within normal body temperature), while maintaining properties of high viscosity and retrogradation [29]. This advantage allows cells, biomolecules and drugs to be loaded in situ into porous architectures made of different materials while preserving high cell viability and molecular activity, which is challenging to achieve for many other fabrication techniques [30].…”

In situ Enabling Approaches for Tissue Regeneration: Current Challenges and New Developments

“…This system conferred a temporary protection for the cells delivery (C2C12 cell line) to produce a fibrous cell-laden hybrid biograft (Weidenbacher et al, 2017). In situ thermoresponsive hydrogels composed of thermogelling macromers (TGM) of Poly(N-isopropylacrylamide) (pNiPAAm) sprayed with a high polyamidoamine (PAMAM) concentration at low pressure with encapsulated cells were deposited using single-stream, layer-by-layer, and dual-stream spraying as coatings on interior intestinal porcine tissue, to create a homogeneous therapeutic coating on the area to further treat lesions triggered by inflammatory bowel disease (Figure 3) (Pehlivaner et al, 2016).…”

“…(III) Fluorescence microscopy image of live(green)/dead(red)-treated sections of 10 wt% TGM and 10 wt% PAMAM hydrogels sprayed at 0.5 bar with dual-stream method. (IV) Images of (A) porcine intestinal tissue and (B) hydrogel formation on tissue after spraying for 1 min, scale bar: 1 cm(Pehlivaner et al, 2016).…”