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. 2021 May 3;9:660145. doi: 10.3389/fbioe.2021.660145

TABLE 2.

Different scaffolds to deliver cell therapies for wound healing.

Delivery method Benefits Limitations Citations
Alginate hydrogel – Mechanical properties of hydrogel can be tuned – Limited long-term stability in physiologic conditions Percival and McCarty, 2015; Aderibigbe and Buyana, 2018; Salehi et al., 2020; Zhang and Zhao, 2020; Zhang et al., 2020
– Establish a robust microenvironment for cells – Must be modified with an adhesive ligand
Collagen hydrogel – Primary organic constituent of native ECM – Damage to its covalent cross-links upon extraction weakens hydrogels, which can then disintegrate on handling or under the pressure of surrounding tissues in vivo. Helary et al., 2012; Chattopadhyay and Raines, 2014; Chen et al., 2018; Stoica et al., 2020
– Highly biocompatible and cytocompatible, amenable to cell adhesion without modification
Fibrin hydrogel – Natural role as a matrix involved in hemostasis and wound healing – Fibrin can be especially susceptible to protease-mediated degradation Ahmed et al., 2007; Janmey et al., 2009; Moreno-Arotzena et al., 2015; Murphy et al., 2017
– Can trigger encapsulated cells to secrete ECM components and reparative growth factors
Hyaluronic acid (HA) hydrogel – Chemical tunability – In modifications like cross-linked HA-aldehyde or HA-amine derivatives, there are disadvantages: the modification procedure involves many synthesis and purification steps, and the crosslinking chemistries that occur upon mixing are hard to control and yield inconsistent gels Baier Leach et al., 2003; Silva et al., 2016
– Favorable mechanical properties, biocompatibility, and biodegradation capacity
Poly(dimethylsiloxane) (PDMS) – Fosters viability and proliferation of seeded ASCs – Poor biocompatibility Schaffer et al., 1994; Razavi and Thakor, 2018
Poly-(ethylene glycol) (PEG) – Versatility in chemical modification and ability to finely tune mechanical properties – Synthesized in combination with natural polymers or biomimetic peptides as lack the biochemical properties for cellular interaction Zhu and Marchant, 2011
Poly(lactic-co-glycolic acid) (PLGA) – Extensively studied – Poor biocompatibility Uematsu et al., 2005; Sadeghi-Avalshahr et al., 2017
– One of the most widely used polymers for materials science engineering applications – Challenging to fixate within wound bed
Poly(methyl methacrylate) (PMMA) – Highly crosslinked gels possess longer degradation times – In general, highly crosslinked gels possess longer degradation times Henderson et al., 2010
Pullulan-collagen hydrogel – Best approximate the porous ultrastructure of native reticular ECM – It is possible that the hydrogel microenvironment is hypoxic Wong et al., 2011b; Rustad et al., 2012
– Easy engineering of the mechanical properties
– Able to support the growth of multiple cell types
– Minimal rejection and favorable biomaterial-tissue integration
Gelatin hydrogel – Excellent biocompatibility – Accelerated biodegradation compared to other hydrogels Kang and Park, 2021
– Ease of chemical modification – Variation between synthesized bathes
– Weak mechanical properties