Sustained Release of Curcumin from Cur-LPs Loaded Adaptive Injectable Self-Healing Hydrogels

Abstract

Biological tissue defects are typically characterized by various shaped defects, and they are prone to inflammation and the excessive accumulation of reactive oxygen species. Therefore, it is still urgent to develop functional materials which can fully occupy and adhere to irregularly shaped defects by injection and promote the tissue repair process using antioxidant and anti-inflammatory mechanisms. Herein, in this work, phenylboronic acid modified oxidized hyaluronic acid (OHAPBA) was synthesized and dynamically crosslinked with catechol group modified glycol chitosan (GCHCA) and guar gum (GG) into a hydrogel loaded with curcumin liposomes (Cur-LPs) which were relatively uniformly distributed around 180 nm. The hydrogel possessed rapid gelation within 30 s, outstanding injectability and tissue-adaptive properties with self-healing properties, and the ability to adhere to biological tissues and adapt to tissue movement. Moreover, good biocompatibility and higher DPPH scavenging efficiency were illustrated in the hydrogel. And a more sustainable release of curcumin from Cur-LPs-loaded hydrogels, which could last for 10 days, was achieved to improve the bioavailability of curcumin. Finally, they might be injected to fully occupy and adhere to irregularly shaped defects and promote the tissue repair process by antioxidant mechanisms and the sustained release of curcumin for anti-inflammation. And the hydrogel would have potential application as candidates in tissue defect repair.

Keywords: antioxidant and anti-inflammatory; injectable adhesive self-healing hydrogel; repair of biological tissue defect; sustainable release of curcumin.

Figure 1

(a) Preparation of OHAPBA; (b) preparation of GCHCA; (c) structure diagram of GG; (d) preparation of the hydrogel and schematic diagram of the dynamic networks.

Figure 2

(a) DLS; (b) TEM; (c) UV-vis spectrum of Cur-LPs; (d) standard curve of curcumin.

Figure 3

(a) ¹H NMR spectroscopy of OHAPBA, OHA and HA; (b) fluorescence spectroscopy of OHAPBA with GCHCA and GG.

Figure 4

(a) Gelation process by inverted method; (b) injectable performance; (c) shear-thinning behavior; (d) swelling ratios; (e) G′ and G″ changes versus strain. (* p < 0.05 significant, ** p < 0.01 very significant).

Figure 5

(a) Self-healing property illustrated by two-cracked hydrogel pieces; (b) G′ and G″ recovery after four cycles of alternating strain; (c) schematic diagram of the self-healing mechanism; (d) adhesive property, adaptability on finger skin of the hydrogel and typical reaction of hydrogel adhesion on tissue.

Figure 6

(a) Cell viability calculated from CCK-8 results; (b) hemolytic property; (c) DPPH scavenging ratio; (d) release of curcumin from Cur-LPs-loaded hydrogel. (** p < 0.01 very significant).