Figure 2.

Shear-thinning hydrogel for injectable encapsulation and long-term delivery (SHIELD), a modified mixing-induced two-component hydrogel (MITCH) with optimal shear moduli that mechanically protects cells during injection and allows injectable cell encapsulation and long-term delivery.^[40a] (A) Schematic of SHIELD hydrogel components. A star-shaped poly(ethylene glycol)(PEG) copolymer incorporated with the proline-rich peptide EYPPYPPPPYPSGC (component 1) forms a weak physical hydrogel with a recombinant C7 linear protein copolymer bearing CC43 WW-domain (component 2) ^[35]. Poly(N-isopropylacrylamide) (PNIPAM) is also incorporated to component 1, and undergoes a second crosslinking at body temperature to strengthen the hydrogel and prolong cell retention in vivo. (B) Increasing PNIPAM incorporation increased the storage (G’) and loss moduli (G”) at body temperature (37 °C). SHIELD-0, SHIELD-0.7, and SHIELD-1 are hydrogels formed with 0, 0.7, and 1 wt% incorporated PNIPAM. (C) SHIELD hydrogels provide more protection to cells passed through a 28-G needle at 1.0 mL/min that does phosphate-buffered saline (PBS). Fluorescent LIVE/DEAD staining performed on human adipose derived stem cells injected with SHIELD-1 hydrogel and PBS. When delivered with the SHIELD hydrogel, cell survival was substantially increased. (D) Cell retention after transplantation via injection evaluated using bioluminescence imaging. SHIELD-1 and SHIELD-0.7 hydrogels significantly increased cell retention up to 14 days after injection compared to the PBS control and the MITCH hydrogel without PNIPAM.

(A–D) Reproduced with permission. ^[35] Copyright 2015, John Wiley and Sons.