The versatile electrospinning technique is recognized as an efficient strategy to deliver active pharmaceutical ingredients and has gained tremendous progress in drug delivery, tissue engineering, cancer therapy, and disease diagnosis. Numerous drug delivery systems fabricated through electrospinning regarding the carrier compositions, drug incorporation techniques, release kinetics, and the subsequent therapeutic efficacy are presented herein. Targeting for distinct applications, the composition of drug carriers vary from natural/synthetic polymers/blends, inorganic materials, and even hybrids. Various drug incorporation approaches through electrospinning are thoroughly discussed with respect to the principles, benefits, and limitations. To meet the various requirements in actual sophisticated in vivo environments and to overcome the limitations of a single carrier system, feasible combinations of multiple drug-inclusion processes via electrospinning could be employed to achieve programmed, multi-staged, or stimuli-triggered release of multiple drugs. The therapeutic efficacy of the designed electrospun drugeluting systems is further verified in multiple biomedical applications and is comprehensively overviewed, demonstrating promising potential to address a variety of clinical challenges.
Nanocellulose
has been demonstrated as a suitable material for
cell culturing, given its similarity to extracellular matrices. Taking
advantage of the shear thinning behavior, nanocellulose suits three-dimensional
(3D) printing into scaffolds that support cell attachment and proliferation.
Here, we propose aqueous suspensions of acetylated nanocellulose of
a low degree of substitution for direct ink writing (DIW). This benefits
from the heterogeneous acetylation of precursor cellulosic fibers,
which eases their deconstruction and confers the characteristics required
for extrusion in DIW. Accordingly, the morphology of related 3D-printed
architectures and their performance during drying and rewetting as
well as interactions with living cells are compared with those produced
from typical unmodified and TEMPO-oxidized nanocelluloses. We find
that a significantly lower concentration of acetylated nanofibrils
is needed to obtain bioinks of similar performance, affording more
porous structures. Together with their high surface charge and axial
aspect, acetylated nanocellulose produces dimensionally stable monolithic
scaffolds that support drying and rewetting, required for packaging
and sterilization. Considering their potential uses in cardiac devices,
we discuss the interactions of the scaffolds with cardiac myoblast
cells. Attachment, proliferation, and viability for 21 days are demonstrated.
Overall, the performance of acetylated nanocellulose bioinks opens
the possibility for reliable and scale-up fabrication of scaffolds
appropriate for studies on cellular processes and for tissue engineering.
A biomaterial system incorporating nanocellulose, poly(glycerol sebacate), and polypyrrole is introduced for the treatment of myocardial infarction. Direct ink writing of the multicomponent aqueous suspensions allows multifunctional lattice structures that not only feature elasticity and electrical conductivity but enable cell growth. They are proposed as cardiac patches given their biocompatibility with H9c2 cardiomyoblasts, which attach extensively at the microstructural level, and induce their proliferation for 28 days. Two model drugs (3i-1000 and curcumin) are investigated for their integration in the patches, either by loading in the precursor suspension used for extrusion or by direct impregnation of the as-obtained, dry lattice. In studies of drug release conducted for five months, a slow in vitro degradation of the cardiac patches is observed, which prevents drug burst release and indicates their suitability for long-term therapy. The combination of biocompatibility, biodegradability, mechanical strength, flexibility, and electrical conductivity fulfills the requirement of the highly dynamic and functional electroresponsive cardiac tissue. Overall, the proposed cardiac patches are viable alternatives for the regeneration of myocardium after infarction through the effective integration of cardiac cells with the biomaterial.
Bone tissue engineering is considered an alternative approach for conventional strategies available to treat bone defects. In this study, we have developed bone scaffolds composed of hydroxyapaptite (HAp), gelatin and mesoporous silica, all recognized as promising materials in bone tissue engineering due to favorable biocompatibility, osteoconductivity and drug delivery potential, respectively. These materials were coupled with conductive polypyrrole (PPy) polymer to create a novel bone scaffold for regenerative medicine. Conductive and non-conductive scaffolds were made by slurry casting method and loaded with a model antibiotic, vancomycin (VCM). Their properties were compared in different experiments in which scaffolds containing PPy showed good mechanical properties, higher protein adsorption and higher percentage of VCM release over a long duration of time compared to non-conductive scaffolds. Osteoblast cells were perfectly immersed into the gelatin matrix and remained viable for 14 days. Overall, new conductive composite bone scaffolds were created and the obtained results strongly verified the applicability of this conductive scaffold in drug delivery, encouraging its further development in tissue engineering applications.
Heart tissue engineering
is critical in the treatment of myocardial infarction, which may benefit
from drug-releasing smart materials. In this study, we load a small
molecule (3i-1000) in new biodegradable and conductive patches for
application in infarcted myocardium. The composite patches consist
of a biocompatible elastomer, poly(glycerol sebacate) (PGS), coupled
with collagen type I, used to promote cell attachment. In addition,
polypyrrole is incorporated because of its electrical conductivity
and to induce cell signaling. Results from the in vitro experiments
indicate a high density of cardiac myoblast cells attached on the
patches, which stay viable for at least 1 month. The degradation of
the patches does not show any cytotoxic effect, while 3i-1000 delivery
induces cell proliferation. Conductive patches show high blood wettability
and drug release, correlating with the rate of degradation of the
PGS matrix. Together with the electrical conductivity and elongation
characteristics, the developed biomaterial fits the mechanical, conductive,
and biological demands required for cardiac treatment.
Biopolymeric patches show enormous potential for the regeneration of infarcted myocardium tissues. However, most of them usually lack appropriate mechanical performance, stability in water, and important functionalities; for instance, antioxidant activity. Protein nanofibrils, such as lysozyme nanofibrils (LNFs), are biocompatible nanostructures with excellent mechanical performance, water insolubility, and antioxidant activity exploited to fabricate materials for different biomedical applications. In this study, LNFs are used to produce gelatin electrospun nanocomposite cardiac patches with improved properties. The addition of the LNFs to the gelatin electrospun patches enhance their mechanical properties, increasing the patches Young's modulus from 3 to 6 MPa, in their wet state, which agrees with the requirements of myocardial contractility. Additionally, it is observed an increment of the antioxidant activity to 80%, by adding only 5% (w/w) of LNFs, and the bioresorbability rate is shortened to 30-35 d, compared to 45 d for the gelatin-only patches, while maintaining their morphology, and biocompatibility toward cardiomyoblasts and fibroblasts. Furthermore, 15% of a model drug is burst released from the patches and preserved for 21 d. Overall, these results demonstrate that LNFs have a great potential as functional reinforcements to fabricate biopolymeric electrospun patches for myocardial infarcted tissue regeneration.
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