Since the traditional 2D surface for cell growth has been shown to be increasingly insufficient in contemporary cell biology, more and more research is performed on 3D matrices that can better represent the natural extracellular matrix (ECM) in many aspects. To create such a complex nonuniform 3D matrix, four-armed polyethylene glycol with azides and (1R,8S,9S)-bicyclo[6.1.0]non-4-yn-9-yl groups is functionalized to form the hydrogel basis. Together with these, a matrix metalloproteinase cleavable peptide sequence as a functional motif is also built in to add degradability to the hydrogel. In addition, self-assembled peptide amphiphile (PA) fibers containing a cellular binding peptide sequence (RGDS) are encapsulated in the hydrogel to mimic the natural fibrous structure of the ECM and to stimulate cell adhesion. Rheology studies confirm that the polymer dissolved in the PA fiber solution forms a stable hydrogel with acceptable mechanical properties (G′ = 3.8 kPa). In addition, it is shown that this hydrogel network is degradable under the action of a metalloproteinase enzyme. Finally, the hybrid hydrogel is used to culture and it is demonstrated that both HeLa cells and human mesenchymal stem cells show adherence, good viability, and a well-spread shape inside the hybrid hydrogel after 5 days of incubation when all components are present.

Hydrogels are water-saturated polymer networks and extensively used in drug delivery, tissue repair engineering, and cell cultures. For encapsulation of drugs or cells, the possibility to form hydrogels in situ is very much desired. This can be achieved in numerous ways, including use of bioorthogonal chemistry to create polymer networks. Here we report a set of bioorthogonally clickable polymers that was designed with the aim to find a combination that could rapidly encapsulate cells in a three-dimensional manner to improve the preparation of hydrogels as tissue mimics. To this end, tetrazine (Tet), trans-cyclooctene (TCO), azide (N3), dibenzocyclooctyne (DBCO), bicyclo[6.1.0]­nonyne (BCN), 3,4-dihydroxyphenylacetic acid (DHPA), and norbornene (Norb) were grafted to four-armed poly­(ethylene)­glycol (star-PEG) polymers of 10 kDa. Inverted vial tests and rheology demonstrated that hydrogels formed within seconds from combinations of TCO-Tet, BCN-DHPA, and BCN-Tet. Hydrogels from DBCO-N3, DBCO–DHPA, and BCN-N3 formed in the range of minutes, whereas the Norb-Tet ligation required multiple hours to form a gel. After this comparison, we chose to prepare hydrogels via DBCO-N3 and BCN-N3 and employed them for human mesenchymal stem cell (HMSC) cultures for a period of 5 days. We additionally incorporated RGDS and MMP cleavable peptide (MMPcp) motifs in these gels to stimulate cell adhesion and add degradability. Both DBCO and BCN gel systems including the functional peptide motifs allowed HMSCs to be viable and spread in 5 days. The DBCO-based hydrogel could trap cells at different depths due to its fast gelation process, while the slower gelation of the BCN-based hydrogel led to cell sedimentation.

The biocompatible, injectable and high water-swollen nature of dual cross-linked hydrogels makes them a popular candidate to imitate the extracellular matrix (ECM) for tissue engineering both in vitro and in vivo.

Fibrous membranes of poly(ɛ-caprolactone)/γ-poly(glutamicacid) (PCL/γ-PGA) composites were successfully produced via an electrospinning process. In doing so, the water solubility of florfenicol (FF) could be enhanced and the drug release properties of FF could be controlled. The mechanical, morphologic, and thermal properties of the fibrous membranes of PCL/γ-PGA were studied by using an electronic single fiber strength machine, scanning electron microscopy, and differential scanning calorimetry. The wettability of the fibrous membranes of PCL/γ-PGA was also measured as discussed in the subsequent section. Fourier transform infrared spectroscopy was applied in the structural analysis of the PCL/γ-PGA-FF fibrous membranes. The results indicated that FF was well blended in the composite membranes of PCL/γ-PGA. In vitro dissolution tests showed that PCL/γ-PGA (85/15; 8%) as both a biodegradable and biocompatible blend may improve the solubility of FF. Therefore, fibrous membranes of PCL/γ-PGA may represent ideal materials for the controlled drug release in various clinical applications.

In this study, poly(D,L-lactic acid)–polyethylene glycol–poly(D,L-lactic acid), hereafter referred to as PDLLA–PEG–PDLLA, triblock copolymer membranes were prepared by electrospinning. Scanning electron microscopy images revealed the morphology of the microfibers, which had a diameter ranging from 300 to 900 nm. Fourier transform infrared spectroscopy was employed for structural analysis of the PDLLA–PEG–PDLLA/florfenicol (FF) membranes, which exhibited three absorption peaks at 3455, 1684, and 1533 cm−1, respectively, indicating that the triblock copolymer and FF are very well blended in the composite membranes. Differential scanning calorimetry revealed that weak interaction possibly decreased the activity of the segment and elevated the T g from 43 °C to 46 °C. From the in vitro dissolution tests, PDLLA as a biodegradable and biocompatible polymer can improve the solubility of FF. The rate of drug release increased with increasing PEG proportion. Furthermore, tensile and nanoindentation tests demonstrated that nanofibers exhibit mechanical properties such as tensile stress (700–2800 KPa), strain (40–120%), and good toughness (0.28–0.98 GPa). In conclusion, PDLLA–PEG–PDLLA nanofibers as a carrier improve the solubility of FF and control drug release.