Abstract
The capacity of a biomaterial to innately modulate cell behavior while meeting the mechanical property requirements of the implant is a much sought-after goal within bioengineering. Here we covalently incorporate soluble elastin into a gelatin–poly (ethylene glycol) (PEG) hydrogel for three-dimensional (3D) cell encapsulation to achieve these properties. The inclusion of elastin into a previously optimized gelatin–PEG hydrogel was then evaluated for effects on entrapped fibroblasts, with the aim to assess the hydrogel as an extracellular matrix (ECM)-mimicking 3D microenvironment for cellular guidance. Soluble elastin was incorporated both physically and covalently into novel gelatin/elastin hybrid PEG hydrogels with the aim to harness the cellular interactivity and mechanical tunability of both elastin and gelatin. This design allowed us to assess the benefits of elastin-containing hydrogels in guiding fibroblast activity for evaluation as a potential dermal replacement. It was found that a gelatin–PEG hydrogel with covalently conjugated elastin, supported neonatal fibroblast viability, promoted their proliferation from 7.3% to 13.5% and guided their behavior. The expression of collagen alpha-1(COL1A1) and elastin in gelatin/elastin hybrid gels increased 16-fold and 6-fold compared to control sample at day 9, respectively. Moreover, cells can be loaded into the hydrogel precursor solution, deposited, and the matrix cross-linked without affecting the incorporated cells adversely, thus enabling a potential injectable system for dermal wound healing.
Highlights
Two important considerations in the design of cell bearing scaffolds are the ability of the scaffold material to influence the functionality of the entrapped cells and secondly, to meet the mechanical property requirements for the scaffold [1,2]
We found that the attachment and viability of fibroblasts in PEG hydrogels were improved with the inclusion of gelatin at a minimum concentration of ~2.3%
The conjugation of gelatin–PEG–acrylate and elastin–PEG–acrylate was confirmed by 1 H Nuclear magnetic resonance (NMR) spectroscopy (Figure 2)
Summary
Two important considerations in the design of cell bearing scaffolds are the ability of the scaffold material to influence the functionality of the entrapped cells and secondly, to meet the mechanical property requirements for the scaffold [1,2]. Cell responses can be guided by cues incorporated into the scaffold. These cues can be chemical, biological, and physical in nature [3]. They mediate effects such as cellular attachment, migration, spreading, proliferation, phenotype, and extracellular matrix (ECM) remodeling [4,5]. Within natural ECM, certain motifs play a crucial instructive role in coercing cell behavior and function and such components can be exploited for biomimetic design and fabrication of scaffold biomaterials [1,6,7,8].
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