Injectable hydrogels for cartilage and bone tissue regeneration: A review.

Annually, millions of patients suffer from irreversible injury owing to the loss or failure of an organ or tissue caused by accident, aging, or disease. The combination of injectable hydrogels and the science of stem cells have emerged to address this persistent issue in society by generating minimally invasive treatments to augment tissue function. Hydrogels are composed of a cross-linked network of polymers that exhibit a high-water retention capacity, thereby mimicking the wet environment of native cells. Due to their inherent mechanical softness, hydrogels can be used as needle-injectable stem cell carrier materials to mend tissue defects. Hydrogels are made of different natural or synthetic polymers, displaying a broad portfolio of eligible properties, which include biocompatibility, low cytotoxicity, shear-thinning properties as well as tunable biological and physicochemical properties. Presently, novel ongoing developments and native-like hydrogels are increasingly being used broadly to improve the quality of life of those with disabling tissue-related diseases. The present review outlines various future and in-vitro applications of injectable hydrogel-based biomaterials, focusing on the newest ongoing developments of in-situ forming injectable hydrogels for bone and cartilage tissue engineering purposes.

Composite Graded Melt Electrowritten Scaffolds for Regeneration of the Periodontal Ligament-to-Bone Interface.

Periodontitis is a ubiquitous chronic inflammatory, bacteria-triggered oral disease affecting the adult population. If left untreated, periodontitis can lead to severe tissue destruction, eventually resulting in tooth loss. Despite previous efforts in clinically managing the disease, therapeutic strategies are still lacking. Herein, melt electrowriting (MEW) is utilized to develop a compositionally and structurally tailored graded scaffold for regeneration of the periodontal ligament-to-bone interface. The composite scaffolds, consisting of fibers of polycaprolactone (PCL) and fibers of PCL-containing magnesium phosphate (MgP) were fabricated using MEW. To maximize the bond between bone (MgP) and ligament (PCL) regions, we evaluated two different fiber architectures in the interface area. These were a crosshatch pattern at a 0/90° angle and a random pattern. MgP fibrous scaffolds were able to promote in vitro bone formation even in culture media devoid of osteogenic supplements. Mechanical properties after MgP incorporation resulted in an increase of the elastic modulus and yield stress of the scaffolds, and fiber orientation in the interfacial zone affected the interfacial toughness. Composite graded MEW scaffolds enhanced bone fill when they were implanted in an in vivo periodontal fenestration defect model in rats. The presence of an interfacial zone allows coordinated regeneration of multitissues, as indicated by higher expression of bone, ligament, and cementoblastic markers compared to empty defects. Collectively, MEW-fabricated scaffolds having compositionally and structurally tailored zones exhibit a good mimicry of the periodontal complex, with excellent regenerative capacity and great potential as a defect-specific treatment strategy.

Antibacterial smart hydrogels: New hope for infectious wound management.

Millions of people die annually due to uncured wound infections. Healthcare systems incur high costs to treat wound infections. Tt is predicted to become more challenging due to the rise of multidrug-resistant conditions. During the last decades, smart antibacterial hydrogels could attract attention as a promising solution, especially for skin wound infections. These antibacterial hydrogels are termed 'smart' due to their response to specific physical and chemical environmental stimuli. To deliver different drugs to particular sites in a controlled manner, various types of crosslinking strategies are used in the manufacturing process. Smart hydrogels are designed to provide antimicrobial agents to the infected sites or are built from polymers with inherent disinfectant properties. This paper aims to critically review recent pre-clinical and clinical advances in using smart hydrogels against skin wound infections and propose the next best thing for future trends. For this purpose, an introduction to skin wound healing and disease is presented and intelligent hydrogels responding to different stimuli are introduced. Finally, the most promising investigations are discussed in their related sections. These studies can pave the way for producing new biomaterials with clinical applications.

Combinatorial fluorapatite-based scaffolds substituted with strontium, magnesium and silicon ions for mending bone defects.

In bone tissue engineering, ionic doping using bone-related minerals such as magnesium (Mg) or strontium (Sr) is a promising strategy to make up for the inherent disadvantages (low solubility) of various apatite-based materials (such as fluorapatite (FAp) and hydroxyapatite (HA)). Therefore, some studies in recent years have tried to address the lack-of-methodology to improve the properties of bioceramics in the field. Even though the outcome of the studies has shown some promises, the influence of doped elements on the structures and properties of in-vitro and in-vivo mineralized FAp has not been investigated in detail so far. Thus, it is still an open question mark in the field. In this work, strontium modified fluorapatite (Sr-FAp), magnesium and silicon modified fluorapatite (Mg-SiFAp) bioceramics were synthesized using a mechanical alloying methodology. Results showed that the doped elements could decrease the crystallinity of FAp (56%) to less than 45% and 39% for Sr-FAp and Mg-SiFAp, respectively. Moreover, in-vitro studies revealed that Sr-FAp significantly enhanced osteogenic differentiation of hMSCs, after 21 days of culture, compared to Mg-SiFAp at both osteogenic and normal media. Then, in vivo bone formation in a defect of rat femur filled with a Sr-FAp and Mg-SiFAp compared to empty defect was investigated. Histological analysis revealed an increase in bone formation three weeks after implanting Sr-FAp compared to Mg-SiFAp and the empty defect. These results suggest that compared to magnesium and silicon, strontium ion significantly promotes bone formation in fluorapatite, making it appropriate for filling bone defects.

Flexible and Green Electronics Manufactured by Origami Folding of Nanosilicate-Reinforced Cellulose Paper.

Today's consumer electronics are made from nonrenewable and toxic components. They are also rigid, bulky, and manufactured in an energy-inefficient manner via CO2-generating routes. Though petroleum-based polymers such as polyethylene terephthalate and polyethylene naphthalate can address the rigidity issue, they have a large carbon footprint and generate harmful waste. Scalable routes for manufacturing electronics that are both flexible and ecofriendly (Fleco) could address the challenges in the field. Ideally, such substrates must incorporate into electronics without compromising device performance. In this work, we demonstrate that a new type of wood-based [nanocellulose (NC)] material made via nanosilicate (NS) reinforcement can yield flexible electronics that can bend and roll without loss of electrical function. Specifically, the NSs interact electrostatically with NC to reinforce thermal and mechanical properties. For instance, films containing 34 wt % of NS displayed an increased young's modulus (1.5 times), thermal stability (290 → 310 °C), and a low coefficient of thermal expansion (40 ppm/K). These films can also easily be separated and renewed into new devices through simple and low-energy processes. Moreover, we used very cheap and environmentally friendly NC from American Value Added Pulping (AVAP) technology, American Process, and therefore, the manufacturing cost of our NS-reinforced NC paper is much cheaper ($0.016 per dm-2) than that of conventional NC-based substrates. Looking forward, the methodology highlighted herein is highly attractive as it can unlock the secrets of Fleco electronics and transform otherwise bulky, rigid, and "difficult-to-process" rigid circuits into more aesthetic and flexible ones while simultaneously bringing relief to an already-overburdened ecosystem.

A three-layered hollow tubular scaffold as an enhancement of nerve regeneration potential.

A significant clinical challenge in the surgery of peripheral nervous system injured via accidents and natural disease is development of biomimetic grafts which could potentially promote nerve repair and regeneration. Although various engineered neural tissue scaffolds have been proposed to support the neural cell functions, they have not been able to instantaneously mimic the whole characteristics of endogenous microenvironment. In this study, we proposed a three-layered tubular scaffold which could provide appropriate electrical, mechanical and biological properties for peripheral nerve engineering. While the inter layer was graphene (Gr) embedded alginate-polyvinyl alcohol (AP-Gr) fibrous scaffold with well-defined anisotropy, the outer layer was double network scaffold of polycaprolactone fumarate (PCLF) and eggshell membrane (ESM). These two layers were attached together using a polycaprolactone (PCL) fibrous membrane, a middle layer, via a simple melting process. Results showed that while the electrical conductivity of the three-layered scaffold was similar to that of AP-Gr fibrous layer, the strength of the three-layered scaffold was significantly improved compared to AP-Gr and ESM-PCLF (1.5 and 1.1 times, respectively) attributed to well attachment of the two layers. As a proof-of-concept, PC12 cell attachment, proliferation, and alignment were studied on the developed three-layered scaffold. The majority of the cells (55%) aligned (<20°) along the major axis of fibers features. Furthermore, electrical stimulation revealed positive effect on the alignment of PC12 cells and change in the cell morphology. With the ease of fabrication and mechanical robustness, the three-layered scaffold of AP-Gr and ESM-PCLF might be utilized as a versatile system for the engineering of peripheral nerve tissue.

Hemocompatible and Bioactive Heparin-Loaded PCL-α-TCP Fibrous Membranes for Bone Tissue Engineering.

The combination of bioactive components such as calcium phosphates and fibrous structures are encouraging niche-mimetic keys for restoring bone defects. However, the importance of hemocompatibility of the membranes is widely ignored. Heparin-loaded nanocomposite poly(ε-caprolactone) (PCL)-α-tricalcium phosphate (α-TCP) fibrous membranes are developed to provide bioactive and hemocompatible constructs for bone tissue engineering. Nanocomposite membranes are optimized based on bioactivity, mechanical properties, and cell interaction. Consequently, various concentrations of heparin molecules are loaded within nanocomposite fibrous membranes. In vitro heparin release profiles reveal a sustained release of heparin over the period of 14 days without an initial burst. Moreover, heparin encapsulation enhances mesenchymal stem cell (MSC) attachment and proliferation, depending on the heparin content. It is concluded that the incorporation of heparin within TCP-PCL fibrous membranes provides the most effective cellular interactions through synergistic physical and chemical cues.