Abstract
There are a limited number of stimuli-responsive biomaterials that are capable of delivering customizable dosages of a therapeutic at a specific location and time. This is especially true in tissue engineering and regenerative medicine applications, where it may be desirable for the stimuli-responsive biomaterial to also serve as a scaffolding material. Therefore, the purpose of this study was to engineer a traditionally non-stimuli responsive scaffold biomaterial to be thermally responsive so it could be used for on-demand drug delivery applications. Fibrin hydrogels are frequently used for tissue engineering and regenerative medicine applications, and they were functionalized with thermally labile oligonucleotide tethers using peptides from substrates for factor XIII (FXIII). The alpha 2-plasmin inhibitor peptide had the greatest incorporation efficiency out of the FXIII substrate peptides studied, and conjugates of the peptide and oligonucleotide tethers were successfully incorporated into fibrin hydrogels via enzymatic activity. Single-strand complement oligo with either a fluorophore model drug or platelet-derived growth factor-BB (PDGF-BB) could be released on demand via temperature increases. These results demonstrate a strategy that can be used to functionalize traditionally non-stimuli responsive biomaterials suitable for on-demand drug delivery systems (DDS).
Highlights
The peptide from von Willebrand factor had the second most incorporation into the fibrin hydrogels; there was significant non-specific adsorption of the peptide since there was no significant difference in incorporation efficiency when compared to negative control hydrogels that were prepared without exogenous factor XIII (FXIII) added to the reaction mixture (p = 0.9)
There was no significant difference in fibronectin and vitronectin peptide incorporation compared with their respective negative control hydrogels
This study demonstrates that double-stranded oligonucleotide tethers can be enzymatically incorporated into fibrin hydrogels and the single-strand complement oligo can be released on-demand by a temperature change
Summary
On-demand drug delivery is an important element of the precision medicine approach to treating disease or injury. Precision medicine accounts for biological variability between individuals and subsets of patients when treating diseases and injuries [1,2,3]. This includes differences in personal characteristics (e.g., age, weight, sex, etc.), environment, and genotype and phenotype information, which are known to affect drug sensitivity [4,5,6,7]. The advantages of on-demand drug delivery systems (DDS) in precision medicine are that they are capable of delivering customizable dosages at a specific location and time
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