Biomimetic Platform for Tissue Regeneration

3D-bioprinting for tissue regeneration relies on, among other things, hydrogels with favorable rheological properties. These include shear thinning for cell-friendly extrusion, post-printing structural stability as well as physiologically relevant elastic moduli needed for optimal cell attachment, proliferation, differentiation and tissue maturation. This work introduces a cost-efficient gelatin-methylcellulose based hydrogel whose rheological properties can be independently optimized for optimal printability and tissue engineering. Hydrogel viscosities were designed to present three different temperature regimes: low viscosity for eased cell suspension and printing with minimal shear stress, form fidelity directly after printing and long term structural stability during incubation. Enzymatically crosslinked hydrogel scaffolds with stiffnesses ranging from 5 to 50 kPa were produced, enabling the hydrogel to biomimic cell environments for different types of tissues. The bioink showed high intrinsic cytocompatibility and tissues fabricated by embedding and bioprinting NIH 3T3 fibroblasts showed satisfactory viability. This novel hydrogel uses robust and inexpensive technology, which can be adjusted for implementation in tissue regeneration, e.g., in myocardial or neural tissue engineering. Full article

An aging global population is accelerating the need for better, longer-lasting orthopaedic and dental implants. Additive manufacturing can provide patient-specific, titanium-alloy-based implants with tailored, three-dimensional, bone-like architecture. Studies using two-dimensional substrates have demonstrated that osteoblastic differentiation of bone marrow stromal cells (MSCs) is enhanced on surfaces possessing hierarchical macro/micro/nano-scale roughness that mimics the topography of osteoclast resorption pits on the bone surface. Conventional machined implants with these surfaces exhibit successful osseointegration, but the complex architectures produced by 3D printing make consistent nanoscale surface texturing difficult to achieve, and current line-of-sight methods used to roughen titanium alloy surfaces cannot reach all internal surfaces. Here, we demonstrate a new, non-line-of-sight, gas/solid-reaction-based process capable of generating well-controlled nanotopographies on all open (gas-exposed) surfaces of titanium alloy implants. Dense 3D-printed titanium-aluminum-vanadium (TiAl6V4) substrates were used to evaluate the evolution of surface nanostructure for development of this process. Substrates were either polished to be smooth (for easier evaluation of surface nanostructure evolution) or grit-blasted and acid-etched to present a microrough biomimetic topography. An ultrathin (90 ± 16 nm) conformal, titania-based surface layer was first formed by thermal oxidation (600 °C, 6 h, air). A calciothermic reduction (CaR) reaction (700 °C, 1 h) was then used to convert the surface titania (TiO₂) into thin layers of calcia (CaO, 77 ± 16 nm) and titanium (Ti, 51 ± 20 nm). Selective dissolution of the CaO layer (3 M acetic acid, 40 min) then yielded a thin nanoporous/nanorough Ti-based surface layer. The changes in surface nanostructure/chemistry after each step were confirmed by scanning and transmission electron microscopies with energy-dispersive X-ray analysis, X-ray diffraction, selected area electron diffraction, atomic force microscopy, and mass change analyses. In vitro studies indicated that human MSCs on CaR-modified microrough surfaces exhibited increased protein expression associated with osteoblast differentiation and promoted osteogenesis compared to unmodified microrough surfaces (increases of 387% in osteopontin, 210% in osteocalcin, 282% in bone morphogenic protein 2, 150% in bone morphogenic protein 4, 265% in osteoprotegerin, and 191% in vascular endothelial growth factor). This work suggests that this CaR-based technique can provide biomimetic topography on all biologically facing surfaces of complex, porous, additively manufactured TiAl6V4 implants. Full article

Peritendinous adhesion (PA) around tendons are daunting challenges for hand surgeons. Tenotomy with various sutures are considered classical tendon repair models (TRM) of tendon adhesion as well as tendon healing. However, potential biomimetic therapies such as anti-adhesion barriers and artificial tendon sheaths to avoid recurrence of PA are sometimes tested in these models without considering tendon healing. Thus, our aim is to create a simplified model without sutures in this study by using three 6 mm longitudinal and parallel incisions called the longitudinal incision model (LCM) in the murine flexor tendon. We found that the adhesion score of LCM has no significant difference to that in TRM. The range of motion (ROM) reveals similar adhesion formation in both TRM and LCM groups. Moreover, mRNA expression levels of collagen I and III in LCM shows no significant difference to that in TRM. The breaking force and stiffness of LCM were significantly higher than that of TRM. Therefore, LCM can imitate flexor tendon adhesion formation without sutures compared to TRM, without significant side effects on biomechanics with an easy operation. Full article

In the last few decades, biomimetic concepts have been widely adopted in various biomedical fields, including clinical dentistry. Endodontics is an important sub-branch of dentistry which deals with the different conditions of pulp to prevent tooth loss. Traditionally, common procedures, namely pulp capping, root canal treatment, apexification, and apexigonesis, have been considered for the treatment of different pulp conditions using selected materials. However, clinically to regenerate dental pulp, tissue engineering has been advocated as a feasible approach. Currently, new trends are emerging in terms of regenerative endodontics which have led to the replacement of diseased and non-vital teeth into the functional and healthy dentine-pulp complex. Root- canal therapy is the standard management option when dental pulp is damaged irreversibly. This treatment modality involves soft-tissue removal and then filling that gap through the obturation technique with a synthetic material. The formation of tubular dentine and pulp-like tissue formation occurs when stem cells are transplanted into the root canal with an appropriate scaffold material. To sum up tissue engineering approach includes three components: (1) scaffold, (2) differentiation, growth, and factors, and (3) the recruitment of stem cells within the pulp or from the periapical region. The aim of this paper is to thoroughly review and discuss various pulp-regenerative approaches and materials used in regenerative endodontics which may highlight the current trends and future research prospects in this particular area. Full article

Tissue engineering to develop alternatives for the maintenance, restoration, or enhancement of injured tissues and organs is gaining more and more attention. In tissue engineering, the scaffold used is one of the most critical elements. Its characteristics are expected to mimic the native extracellular matrix and its unique topographical structures. Recently, the topographies of scaffolds have received increasing attention, not least because different topographies, such as aligned and random, have different repair effects on various tissues. In this review, we have focused on various technologies (electrospinning, directional freeze-drying, magnetic freeze-casting, etching, and 3-D printing) to fabricate scaffolds with different topographic orientations, as well as discussed the physicochemical (mechanical properties, porosity, hydrophilicity, and degradation) and biological properties (morphology, distribution, adhesion, proliferation, and migration) of different topographies. Subsequently, we have compiled the effect of scaffold orientation on the regeneration of vessels, skin, neural tissue, bone, articular cartilage, ligaments, tendons, cardiac tissue, corneas, skeletal muscle, and smooth muscle. The compiled information in this review will facilitate the future development of optimal topographical scaffolds for the regeneration of certain tissues. In the majority of tissues, aligned scaffolds are more suitable than random scaffolds for tissue repair and regeneration. The underlying mechanism explaining the various effects of aligned and random orientation might be the differences in “contact guidance”, which stimulate certain biological responses in cells. Full article

Bone is a complex biologic tissue, which is extremely relevant for various physiological functions, in addition to movement, organ protection, and weight bearing. The repair of critical size bone defects is a still unmet clinical need, and over the past decades, material scientists have been expending efforts to find effective technological solutions, based on the use of scaffolds. In this context, biomimetics which is intended as the ability of a scaffold to reproduce compositional and structural features of the host tissues, is increasingly considered as a guide for this purpose. However, the achievement of implants that mimic the very complex bone composition, multi-scale structure, and mechanics is still an open challenge. Indeed, despite the fact that calcium phosphates are widely recognized as elective biomaterials to fabricate regenerative bone scaffolds, their processing into 3D devices with suitable cell-instructing features is still prevented by insurmountable drawbacks. With respect to biomaterials science, new approaches maybe conceived to gain ground and promise for a substantial leap forward in this field. The present review provides an overview of physicochemical and structural features of bone tissue that are responsible for its biologic behavior. Moreover, relevant and recent technological approaches, also inspired by natural processes and structures, are described, which can be considered as a leverage for future development of next generation bioactive medical devices. Full article