TY - JOUR

T1 - A hybrid injectable hydrogel from hyperbranched PEG macromer as a stem cell delivery and retention platform for diabetic wound healing

AU - Xu, Qian

AU - A, Sigen

AU - Gao, Yongsheng

AU - Guo, Linru

AU - Creagh-Flynn, Jack

AU - Zhou, Dezhong

AU - Greiser, Udo

AU - Dong, Yixiao

AU - Wang, Fadang

AU - Tai, Hongyun

AU - Liu, Wenguang

AU - Wang, Wei

AU - Wang, Wenxin

PY - 2018/7/15

Y1 - 2018/7/15

N2 - The injectable hydrogel with desirable biocompatibility and tunable properties can improve the efficacy of stem cell-based therapy. However, the development of injectable hydrogel remains a great challenge due to the restriction of crosslinking efficiency, mechanical properties, and potential toxicity. Here, we report that a new injectable hydrogel system were fabricated from hyperbranched multi-acrylated poly(ethylene glycol) macromers (HP-PEGs) and thiolated hyaluronic acid (HA-SH) and used as a stem cell delivery and retention platform. The new HP-PEGs were synthesized via in situ reversible addition fragmentation chain transfer (RAFT) polymerization using an FDA approved anti-alcoholic drug - Disulfiram (DS) as the RAFT agent precursor. HP-PEGs can form injectable hydrogels with HA-SH rapidly via thiol-ene click reaction under physiological conditions. The hydrogels exhibited stable mechanical properties, non-swelling and anti-fouling properties. Hydrogels encapsulating adipose-derived stem cells (ADSCs) have demonstrated promising regenerative capabilities such as the maintenance of ADSCs’ stemness and secretion abilities. The ADSCs embedded hydrogels were tested on the treatment of diabetic wound in a diabetic murine animal model, showing enhanced wound healing.Statement of significanceDiabetic wounds, which are a sever type of diabetes, have become one of the most serious clinical problem. There is a great promise in the delivery of adipose stem cells into wound sites using injectable hydrogels that can improve diabetic wound healing. Due to the biocompatibility of poly(ethylene glycol) diacrylate (PEGDA), we developed an in situ RAFT polymerization approach using anti-alcoholi drug - Disulfiram (DS) as a RAFT agent precursor to achieve hyperbranched PEGDA (HP-PEG). HP-PEG can form an injectable hydrogel by crosslinking with thiolated hyaluronic acid (HA-SH). ADSCs can maintain their regenerative ability and be delivered into the wound sites. Hence, diabetic wound healing process was remarkably promoted, including inhibition of inflammation, enhanced angiogenesis and re-epithelialization. Taken together, the ADSCs-seeded injectable hydrogel may be a promising candidate for diabetic wound treatment.

AB - The injectable hydrogel with desirable biocompatibility and tunable properties can improve the efficacy of stem cell-based therapy. However, the development of injectable hydrogel remains a great challenge due to the restriction of crosslinking efficiency, mechanical properties, and potential toxicity. Here, we report that a new injectable hydrogel system were fabricated from hyperbranched multi-acrylated poly(ethylene glycol) macromers (HP-PEGs) and thiolated hyaluronic acid (HA-SH) and used as a stem cell delivery and retention platform. The new HP-PEGs were synthesized via in situ reversible addition fragmentation chain transfer (RAFT) polymerization using an FDA approved anti-alcoholic drug - Disulfiram (DS) as the RAFT agent precursor. HP-PEGs can form injectable hydrogels with HA-SH rapidly via thiol-ene click reaction under physiological conditions. The hydrogels exhibited stable mechanical properties, non-swelling and anti-fouling properties. Hydrogels encapsulating adipose-derived stem cells (ADSCs) have demonstrated promising regenerative capabilities such as the maintenance of ADSCs’ stemness and secretion abilities. The ADSCs embedded hydrogels were tested on the treatment of diabetic wound in a diabetic murine animal model, showing enhanced wound healing.Statement of significanceDiabetic wounds, which are a sever type of diabetes, have become one of the most serious clinical problem. There is a great promise in the delivery of adipose stem cells into wound sites using injectable hydrogels that can improve diabetic wound healing. Due to the biocompatibility of poly(ethylene glycol) diacrylate (PEGDA), we developed an in situ RAFT polymerization approach using anti-alcoholi drug - Disulfiram (DS) as a RAFT agent precursor to achieve hyperbranched PEGDA (HP-PEG). HP-PEG can form an injectable hydrogel by crosslinking with thiolated hyaluronic acid (HA-SH). ADSCs can maintain their regenerative ability and be delivered into the wound sites. Hence, diabetic wound healing process was remarkably promoted, including inhibition of inflammation, enhanced angiogenesis and re-epithelialization. Taken together, the ADSCs-seeded injectable hydrogel may be a promising candidate for diabetic wound treatment.

KW - Diabetic wound healing

KW - Hyperbranched polymers

KW - In situ RAFT

KW - Injectable hydrogels

KW - Stem cells

U2 - 10.1016/j.actbio.2018.05.039

DO - 10.1016/j.actbio.2018.05.039

M3 - Article

VL - 75

SP - 63

EP - 74

JO - Acta Biomaterialia

JF - Acta Biomaterialia

SN - 1742-7061

ER -