Design of Protein-Based Liquefied Cell-Laden Capsules with Bioinspired Adhesion for Tissue Engineering


Platforms with liquid cores are extensively explored as cell delivery vehicles for cell-based therapies and tissue engineering. However, the recurrence of synthetic materials can impair its translation into the clinic. Inspired by the adhesive proteins secreted by mussels, liquefied capsule is developed using gelatin modified with hydroxypyridinones (Gel-HOPO), a catechol analogue with oxidant-resistant properties. The protein-based liquefied macrocapsule permitted the compartmentalization of living cells by an approachable and non-time-consuming methodology resorting to i) superhydrophobic surfaces as a processing platform of hydrogel beads, ii) gelation of gelatin at temperatures < 25 degrees C, iii) iron coordination of the hydroxypyridinone (HOPO) moieties at physiological pH, and iv) core liquefaction at 37 degrees C. With the design of a proteolytically degradable shell, the possibility of encapsulating human adipose-derived mesenchymal stem cells (hASC) with and without the presence of polycaprolactone microparticles (mu PCL) is evaluated. Showing prevalence toward adhesion to the inner shell wall, hASC formed a monolayer evidencing the biocompatibility and adequate mechanical properties of these platforms for proliferation, diminishing the need for mu PCL as a supporting substrate. This new protein-based liquefied platform can provide biofactories devices of both fundamental and practical importance for tissue engineering and regenerative medicine or in other biotechnology fields.



subject category

Engineering, Biomedical; Nanoscience & Nanotechnology; Materials Science, Biomaterials


Gomes, MC; Costa, DCS; Oliveira, CS; Mano, JF

our authors


The authors acknowledge the support of the European Research Council for project ATLAS, grant agreement ERC-2014-ADG-669858. This work was developed within the scope of the project CICECO-Aveiro Institute of Materials, UIDB/50011/2020 & UIDP/50011/2020, financed by national funds through the FCT/MEC and when appropriate co-financed by FEDER under the PT2020 Partnership Agreement. This work was also supported by the Programa Operacional Competitividade e InternacionalizacAo (POCI), in the component FEDER, and by national funds (OE) through FCT/MCTES, in the scope of the projects BEAT (PTDC/BTM-MAT/30869/2017) and MARGEL (PTDC/BTM-MAT/31498/2017). The Beat and MARGEL projects are acknowledged for the individual Junior Researcher contracts of M.C.G. and D.C.S.C., respectively. The ATLAS project is acknowledged for the postdoctoral fellowship of C.S.O. M.C.G. also acknowledges

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