Injectable hybrid hydrogel for stem cell delivery and skin wound healing, from PEG-based multifunctional hyperbranched polymers
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1
Stanford University, Department of surgery, United States
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2
University College Dublin, The Charles Institute of Dermatology, Ireland
Introduction: Stem cell therapies have been attracted much attention for the last few decades in the field of regenerative medicine and tissue engineering. Increased evidence indicates that the traditional 2-dimensional (2D) cell culture systems cannot fully mimic the natural tissue microenvironment, advanced 3-dimensional (3D) extracellular matrix (ECM) replacements are required not only for developing our understanding on stem cell behavior, but also for the clinical application.
Materials and Methods: A hyperbranched PEG-based multifunctional polymer was developed via RAFT homopolymerization of the di-vinyl monomer of PEGDA (Figure 1). The rapid gelation (within two minutes) can be achieved between the polymers and thiolated biomaterials (e.g. hyaluronic acid) at physiological condition due to the high degree of multi-acrylate functionality of this polymer (Figure 2). Primary human adipose-derived stem cells (ASCs) were embedded into this in situ crosslinked hydrogels, and the cellular behavior such as the morphology, viability, metabolic activity, proliferation, stemness and paracrine secretion profile were fully evaluated in vitro. Mouse excisional wound model was used to determine the therapeutic effects of this injectable hydrogel based skin substitute for wound healing.
Results and Discussion: The RAFT agent significantly delayed the gelation, and the polymer molecular weight and polymeric architecture could be well controlled by adjusting reaction time and monomer/CTA ratio. It was found that the lower monomer/CTA ratio decreased the intramolecular cyclization and increased the pendent vinyl functional group on the polymer chain. The 3D microenvironment (e.g. chemical and mechanical properties) of this hydrogel can be easily adjusted by altering the polymer characters and the crosslinking conditions. It was showed that the hydrogel maintained the good cell viability and stemness, increased the secretion level of certain growth factors and cytokines, and improved the wound healing process in vivo (Figure 3).
Conclusions: We demonstrated the synthesis of hyperbranched polyPEGDA homopolymers with high degree of acrylate functionality via one-step RAFT homopolymerization approach. An injectable hydrogel can be formed by crosslinking this polymer with a commercially available thiolated biomaterials, and rapid gelation can be achieved under physiological conditions. 3D culture and cellular evaluation studies were performed with embedded ASCs, which indicated the present hydrogel system kept good cell viability and activities in vitro. In addition, such bioactive hydrogel system can be used as an injectable skin substitute and significantly accelerated the wound healing process in a mouse excisional wound model.
Irish Research Council (IRC), ELEVATE programme.
Keywords:
Hydrogel,
Tissue Engineering,
stem cell,
3D scaffold
Conference:
10th World Biomaterials Congress, Montréal, Canada, 17 May - 22 May, 2016.
Presentation Type:
Poster
Topic:
Biomaterials in constructing tissue substitutes
Citation:
Dong
Y,
Khong
S,
Rodrigues
M,
Li
AY,
Zhou
D,
Gao
Y,
Brett
EA,
Wang
W and
Gurtner
GC
(2016). Injectable hybrid hydrogel for stem cell delivery and skin wound healing, from PEG-based multifunctional hyperbranched polymers.
Front. Bioeng. Biotechnol.
Conference Abstract:
10th World Biomaterials Congress.
doi: 10.3389/conf.FBIOE.2016.01.00528
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Received:
27 Mar 2016;
Published Online:
30 Mar 2016.