Crosslinking Strategies for 3D Bioprinting of Polymeric Hydrogels

Three‐dimensional (3D) bioprinting has recently advanced as an important tool to produce viable constructs that can be used for regenerative purposes or as tissue models. To develop biomimetic and sustainable 3D constructs, several important processing aspects need to be considered, among which crosslinking is most important for achieving desirable biomechanical stability of printed structures, which is reflected in subsequent behavior and use of these constructs. In this work, crosslinking methods used in 3D bioprinting studies are reviewed, parameters that affect bioink chemistry are discussed, and the potential toward improving crosslinking outcomes and construct performance is highlighted. Furthermore, current challenges and future prospects are discussed. Due to the direct connection between crosslinking methods and properties of 3D bioprinted structures, this Review can provide a basis for developing necessary modifications to the design and manufacturing process of advanced tissue‐like constructs in future.     

Electrospun multifunctional diclofenac sodium releasing nanoscaffold

Electrospinning is a method utilized to produce nano-scale fibers for tissue engineering applications. A variety of cells are attracted by nano scale surfaces and structures probably due to the similarity of their natural environment scale. In this study, diclofenac sodium (DS) releasing nanofibers were manufactured via electrospinning process. Poly(95 epsilon-capro/5 D,L-lactide) was dissolved into acetic acid to form a 20% w/v solution. 2% w/w of DS was then added into the polymer solution and stirred homogenously. About 1 g of polymer/drug solution was spun onto the collector under electrostatic conditions. The distance between needle tip and sample collector was arranged to 10 cm and applied electric field was 2 kV/cm. Release rate of DS was measured by using UV/VIS spectrophotometer. Resulted highly porous nanofiber scaffold was about 2 mm thick and the diameter of nanofibers was approximately 130 nm. Structure included in also spheres with approximately diameter of 3.30 microm. About 45% of DS was released during the first 24 hours and after that the release decreased to almost zero value. After 35 days release rate increased. This study revealed that manufacturing of highly porous DS releasing nanoscaffold by electrospinning process is feasible. Having fast DS release rate nanofibrous scaffold made of poly(95 epsilon-capro/5 D,L-lactide) can be of benefit for applications where immediate control of tissue reaction is needed.     

Biodegradable nanomats produced by electrospinning: expanding multifunctionality and potential for tissue engineering

With increasing interest in nanotechnology, development of nanofibers (n-fibers) by using the technique of electrospinning is gaining new momentum. Among important potential applications of n-fiber-based structures, scaffolds for tissue-engineering represent an advancing front. Nanoscaffolds (n-scaffolds) are closer to natural extracellular matrix (ECM) and its nanoscale fibrous structure. Although the technique of electrospinning is relatively old, various improvements have been made in the last decades to explore the spinning of submicron fibers from biodegradable polymers and to develop also multifunctional drug-releasing and bioactive scaffolds. Various factors can affect the properties of resulting nanostructures that can be classified into three main categories, namely: (1) Substrate related, (2) Apparatus related, and (3) Environment related factors. Developed n-scaffolds were tested for their cytocompatibility using different cell models and were seeded with cells for to develop tissue engineering constructs. Most importantly, studies have looked at the potential of using n-scaffolds for the development of blood vessels. There is a large area ahead for further applications and development of the field. For instance, multifunctional scaffolds that can be used as controlled delivery system do have a potential and have yet to be investigated for engineering of various tissues. So far, in vivo data on n-scaffolds are scarce, but in future reports are expected to emerge. With the convergence of the fields of nanotechnology, drug release and tissue engineering, new solutions could be found for the current limitations of tissue engineering scaffolds, which may enhance their functionality upon in vivo implantation. In this paper electrospinning process, factors affecting it, used polymers, developed n-scaffolds and their characterization are reviewed with focus on application in tissue engineering.     

Tyrosine derived polycarbonate membrane is useful for guided bone regeneration in rabbit mandibular defects

Standardized bilateral through-and-through defects (12 × 6 mm) were created extraorally in the mandibular angle of 18 New Zealand White rabbits. Animals were divided in to three groups (n = 6) according to the intended healing time. On the left side, defects were covered with a poly(desaminotyrosyl-tyrosine-ethyl ester carbonate) (PDTE carbonate) membrane wrapped around the inferior border of the mandible and fixed with bioabsorbable sutures. On the right side, the defects were filled with a mesh made of bioactive glass 13–93 and 3 wt% chitosan. The defects were covered with the same membranes. Periosteal flap was sutured over the membrane. Radiographically, bone ingrowth was seen in all specimens at 12 weeks postoperatively. At 24 weeks, completely ossified area remained approximately at the same level as at 12 weeks, but the non-ossified area decreased to almost zero. However, the bioactive glass mesh did not improve the results. Nevertheless, enveloping the defect with PDTE carbonate membrane seemed to play a crucial role in new bone formation. Based on these results, we conclude that tyrosine polycarbonate is a promising new material for guided bone regeneration.     

Room-Temperature-Formed PEDOT:PSS Hydrogels Enable Injectable,Soft, and Healable Organic Bioelectronics

There is an increasing need to develop conducting hydrogels for bioelectronic applications. In particular, poly(3,4-ethylenedioxythiophene):poly(styrenesulfonate) (PEDOT:PSS) hydrogels have become a research hotspot due to their excellent biocompatibility and stability. However, injectable PEDOT:PSS hydrogels have been rarely reported. Such syringe-injectable hydrogels are highly desirable for minimally invasive biomedical therapeutics. Here, an approach is demonstrated to develop injectable PEDOT:PSS hydrogels by taking advantage of the room-temperature gelation property of PEDOT:PSS. These PEDOT:PSS hydrogels form spontaneously after syringe injection of the PEDOT:PSS suspension into the desired location, without the need of any additional treatments. A facile strategy is also presented for large-scale production of injectable PEDOT:PSS hydrogel fibers at room temperature. Finally, it is demonstrated that these room-temperature-formed PEDOT:PSS hydrogels (RT-PEDOT:PSS hydrogel) and hydrogel fibers can be used for the development of soft and self-healable hydrogel bioelectronic devices.     

Hydrogel‐Enabled Transfer‐Printing of Conducting Polymer Films for Soft Organic Bioelectronics

The use of conducting polymers such as poly(3,4‐ethylenedioxythiophene) polystyrene sulfonate (PEDOT:PSS) for the development of soft organic bioelectronic devices, such as organic electrochemical transistors (OECTs), is rapidly increasing. However, directly manipulating conducting polymer thin films on soft substrates remains challenging, which hinders the development of conformable organic bioelectronic devices. A facile transfer‐printing of conducting polymer thin films from conventional rigid substrates to flexible substrates offers an alternative solution. In this work, it is reported that PEDOT:PSS thin films on glass substrates, once mixed with surfactants, can be delaminated with hydrogels and thereafter be transferred to soft substrates without any further treatments. The proposed method allows easy, fast, and reliable transferring of patterned PEDOT:PSS thin films from glass substrates onto various soft substrates, facilitating their application in soft organic bioelectronics. By taking advantage of this method, skin‐attachable tattoo‐OECTs are demonstrated, relevant for conformable, imperceptible, and wearable organic biosensing.     

Synthesis,characterization, and comparison of self‐doped,doped, and undoped forms of polyaniline,poly(o‐anisidine), and poly[aniline‐co‐(o‐anisidine)]

Polyaniline (PANI), poly(o‐anisidine), and poly[aniline‐co‐(o‐anisidine)] were synthesized by chemical oxidative polymerization with ammonium persulfate as an oxidizing reagent in an HCl medium. The viscosities, electrical conductivity, and crystallinity of the resulting polymers (self‐doped forms) were compared with those of the doped and undoped forms. The self‐doped, doped, and undoped forms of these polymers were characterized with infrared spectroscopy, ultraviolet–visible spectroscopy, and a four‐point‐probe conductivity method. X‐ray diffraction characterization revealed the crystalline nature of the polymers. The observed decrease in the conductivity of the copolymer and poly(o‐anisidine) with respect to PANI was attributed to the incorporation of the methoxy moieties into the PANI chain. The homopolymers attained conductivity in the range of 3.97 × 10^?3 to 7.8 S/cm after doping with HCl. The conductivity of the undoped forms of the poly[aniline‐co‐(o‐anisidine)] and poly(o‐anisidine) was observed to be lower than 10^?5 J/S cm^?1. The conductivity of the studied polymer forms decreased by the doping process in the following order: self‐doped → doped → undoped. The conductivity of the studied polymers decreased by the monomer species in the following order: PANI → poly[aniline‐co‐(o‐anisidine)] → poly(o‐anisidine). All the polymer samples were largely amorphous, but with the attachment of the pendant groups of anisidine to the polymer system, the crystallinity region increased. The undoped form of poly[aniline‐co‐(o‐anisidine)] had good solubility in common organic solvents, whereas doped poly[aniline‐co‐(o‐anisidine)] was moderately crystalline and exhibited higher conductivity than the anisidine homopolymer. © 2005 Wiley Periodicals, Inc. J Appl Polym Sci, 2006