Selection of natural biomaterials for micro-tissue and organ-on-chip models

The desired organ in micro-tissue models of organ-on-a-chip (OoC) devices dictates the optimum biomaterials, divided into natural and synthetic biomaterials. They can resemble biological tissues' biological functions and architectures by constructing bioactivity of macromolecules, cells, nanoparticles, and other biological agents. The inclusion of such components in OoCs allows them having biological processes, such as basic biorecognition, enzymatic cleavage, and regulated drug release. In this report, we review natural-based biomaterials that are used in OoCs and their main characteristics. We address the preparation, modification, and characterization methods of natural-based biomaterials and summarize recent reports on their applications in the design and fabrication of micro-tissue models. This article will help bioengineers select the proper biomaterials based on developing new technologies to meet clinical expectations and improve patient outcomes fusing disease modeling

Poly(2-ethyl-2-oxazoline-co-ethyleneimine)-block-poly(epsilon-caprolactone) based micelles: synthesis, characterization, peptide conjugation and cytotoxic activity

Here we present self-assembled polymeric micelles as potential delivery systems for therapeutic agents with highly tunable properties. The major goal of this study is to design breast and prostate cancer specific targeting peptide modified PEtOx-co-PEI-b-PCL block copolymer based micelles as a targetable carrier system in cancer treatment. For this, a series of micelles based on poly(2-ethyl-2-oxazoline)-co-polyethyleneimine-block-poly(epsilon-caprolactone) [P(EtOx-co-EI)-b-PCL] copolymers with two different proportions of PEI (30% and 60% hydrolysis degrees of PEtOx) were successfully prepared. The block copolymers were synthesized using a combination of living cationic ring-opening polymerization and a copper(i)-catalyzed azide-alkyne cycloaddition (CuAAC) click reaction. Then, peptide 18 and peptide 563 were conjugated to P(EtOx-co-EI)-b-PCL through a thiol-ene click-type reaction to obtain the desired tumor-targeting. The structural properties of the copolymers were confirmed by H-1 NMR, FT-IR, UV-Vis spectrometry and GPC. Peptide and non-peptide-conjugated micelles with particle sizes between 82 +/- 0.6 and 170 +/- 10.7 nm were obtained by self-assembly with two different chain lengths of PEI blocks. The micelles containing the 60% PEI block showed increased zeta potential values. The cytotoxicity of the copolymers was evaluated under in vitro conditions. Overall, our results indicate that the micelles prepared with peptide-conjugated block copolymers can be used as potential nanocarriers for targeted therapeutic delivery systems

Hybrid Stromal Vascular Fraction (Hybrid-SVF): A New Paradigm in Mechanical Regenerative Cell Processing

Background:. Enzymatic digestion of extracellular matrix (ECM) from lipoaspirate is the conventional form of harvesting stromal vascular fraction (SVF) called enzymatically digested SVF (E-SVF). Mechanical SVF (M-SVF) isolation has emerged as an alternative method, but it has also some limitations in terms of lower cell viability and diminished cell counts. To enhance the SVF qualitatively and quantitatively, we propose a novel concept called "hybrid-SVF,” in which we combine M-SVF with the concentrated parts of adipose tissue after centrifugation, which is called stromal vascular matrix (SVM). Methods:. Hybrid-SVF injection was applied as an adjunctive therapy to fat grafting in 88 patients and 11 samples were evaluated in the laboratory for cell count, viability and cell activity. Results:. Experimental results determined that SVM part showed higher cellular activity. SVM and M-SVF showed higher cellular potency than E-SVF. Clinically, none of the patients required an additional session for fat grafting since there was no significant graft resorption. However, seven patients asked for further volume augmentation due to their individual preferences. No major complication was encountered. Conclusions:. The usage of hybrid-SVF has a very high regenerative potential due to the ECM support and exceptionally high cell yield in addition to preserved cell potency. Although there are ongoing studies focusing on optimizing cell counts and further clinical applications, we believe that our preliminary results might create a paradigm shift in the area of regenerative fat grafting

Synthesis, biocompatibility and gene encapsulation of poly(2-Ethyl 2-Oxazoline)-dioleoyl phosphatidylethanolamine (PEtOx-DOPE) and post-modifications with peptides and fluorescent dye coumarin

Liposome surface modifications serve great potential applications of liposomes, for instance, increasing stability, bioactive liposome conjugates, and targeted drug, gene, and image agent delivery. In this study, novel targeted lipopolymers, peptide 18/peptide 563-poly(2-ethyl-2-oxazoline)-dioleoylphosphatidyl-ethanolamine (P18/P563-PEtOx-DOPE), have been demonstrated to be successfully synthesized. The structures of P18/P563-PEtOx-DOPE were confirmed by FT-IR spectroscopy, GPC, and(1)H-NMR. In this strategy, poly(2-ethyl 2-oxazoline)-modified liposomes were firstly constructed with molecular weights of 3,500 and 5,800 Da. Then, we chose PEtOx(5800)-DOPE because it has been obtained better particle size (88.74 +/- 0.6816) according to the DLS results. Then, peptides- and dye-PEtOx lipid-based nanovesicle (LN) were prepared by peptide-18, peptide-563, and 7-mercapto-4-methyl coumarin. Genetic material (pDNA) was encapsulated into the liposomes and evaluated the encapsulation of plasmid DNA with migration by using agarose gel electrophoresis.In vitrocytotoxicity experiment results on prostate cancer and breast cancer cell lines, parallelly with the healthy prostate (PNT1A) and breast (MCF10A) epithelial cell lines, cells showed insignificant toxic effects. Thus, we can suggest a novel PEtOx phospholipid thanks to this article and its integration with ligands, which great potential for gene transfer system