Neuro-bone tissue engineering: Multiple potential translational strategies between nerve and bone.

Numerous tissue regeneration paradigms show evident neurological dependence, including mammalian fingertip, skin, and bone regeneration. The mature skeleton is innervated by an abundant nervous system that infiltrates the developing axial and appendicular bones and maintains the stability of the systemic skeletal system by controlling blood flow, regulating bone metabolism, secreting neurotransmitters, and regulating stem cell behavior. In recent years, neurotization in tissue-engineered bone has been considered as a promising strategy to effectively overcome the challenge of vascularization and innervation regeneration in the central zone of "critical-sized bone defects" that conventional tissue-engineered scaffolds are unable to handle, however, further validation is needed in relevant clinical applications. Therefore, this study reviews the mechanisms by which the nervous system regulates bone metabolism and regeneration through a variety of neurogenic or non-neurogenic factors, as well as the recent progress and design strategies of neuralized tissue-engineered bone, to provide new ideas for further studies on subsequent neural bone tissue engineering. STATEMENT OF SIGNIFICANCE: The interaction of nerve and bone tissue during skeletal development and repair has attracted widespread attention, with emerging evidences highlighting the regulation of bone metabolism and regeneration by the nervous system, but the underlying mechanisms have not been elucidated. Thus, further applications of neuro-bone tissue engineering still needs careful consideration. In this review, we summarize the numerous neurogenic and non-neurogenic factors which are involved in bone repair and regeneration, and further explore the current status of their application and biomaterial design in neuro-bone tissue engineering, and finally discuss the challenge and prospective for neuro-bone tissue engineering to facilitate its further development.

Platinum-based chemotherapy via nanocarriers and co-delivery of multiple drugs.

Platinum-based anticancer drugs can inhibit the growth of cancer cells by disrupting DNA replication, which makes them widely applicable in clinics for treating tumors and cancers. However, owing to the intrinsic or acquired drug resistance and severe side effects caused in the treatment, their successful clinical applications have been limited. Various strategies have been used to address these challenges. Nanocarriers have been used for platinum drug delivery because they can be effectively deposited in tumor tissues to reduce the damage to normal organs for an enhanced permeability and retention (EPR) effect. Furthermore, for synergizing the function of platinum-based drugs with different mechanisms to decrease the toxicities, multicomponent chemotherapy has become an imperative strategy in clinical cancer treatments. This review aims to introduce the mechanisms of action and limitations of platinum-based drugs in clinics, followed by providing the current advancement of nanocarriers including lipids, polymers, dendrimers, micelles and albumin for platinum drug delivery in cancer treatments. In addition, multicomponent chemotherapy based on platinum drugs is introduced in detail. Finally, the prospects of multicomponent chemotherapy for cancer treatment are discussed as well.

Edible Materials in Tissue Regeneration.

Edible materials have attracted increasing attention because of their excellent properties including availability, biocompatibility, biological activity, and biodegradability. Natural polysaccharides, phenolic compounds, and proteins are widely used in tissue regeneration. To better characterize their healing effect, this review article describes the applications of edible materials in tissue regeneration including wound healing and bone tissue regeneration. As an introduction to the topic, their sources and main bioactive properties are discussed. Then, the mechanism by which they facilitate wound healing based on their hemostasis, antibacterial, anti-inflammatory, and antioxidant properties is systematically investigated. Moreover, a more comprehensive discussion is presented on the approaches by which edible materials can be used as scaffolds or agents for the provision of the components of natural bones for regulating the level of osteogenesis-related cytokines to enhance bone repair. Finally, the prospects of edible materials for tissue regeneration are discussed.

Amino Acid- and Growth Factor-Based Multifunctional Nanocapsules for the Modulation of the Local Microenvironment in Tissue Engineering.

Oxidative damage to cells from metabolites at a wound site is one of the trickiest factors inhibiting tissue regeneration, especially with bulk damage. In addition, an excessive inflammatory reaction by the body at the wound site can make it even worse. How to scavenge the reactive oxygen species (ROS) produced from metabolism and inflammatory reactions has become a critical issue in tissue engineering. Here, we utilize the natural bioactive small molecules l-arginine and l-phenylalanine and the growth factor inositol to synthesize a branched poly(ester amide) (BPEA) to fabricate BPEA nanocapsules for vitamin E delivery at wound sites. BPEA nanocapsules loaded with vitamin E (BPEA@VE NCs) could protect cells from both extracellular and intracellular damage by scavenging ROS. Simultaneously, the inflammatory reaction could also be downregulated, benefiting from the introduction of l-arginine. Furthermore, the biodegradation products of BPEA are natural metabolites of the body, such as amino acids and growth factors, guaranteeing the biocompatibility of the BPEA@VE NCs. The protective ability of the BPEA@VE NCs was also investigated in vivo for accelerated wound healing. All the results indicate that the BPEA@VE NCs have promising potential for the modulation of the local microenvironment in tissue engineering for excellent antioxidative and anti-inflammatory properties.

Natural Polymer-Based Hydrogels with Enhanced Mechanical Performances: Preparation, Structure, and Property.

Hydrogels based on natural polymers have bright application prospects in biomedical fields due to their outstanding biocompatibility and biodegradability. However, the poor mechanical performances of pure natural polymer-based hydrogels greatly limit their application prospects. Recently, a variety of strategies has been applied to prepare natural polymer-based hydrogels with enhanced mechanical properties, which generally exhibit stiffening, strengthening, and stretchable behaviors. This article summarizes the recent progress of natural polymer-based hydrogels with enhanced mechanical properties. From a structure point of view, four kinds of hydrogel are reviewed; double network hydrogels, nanocomposite hydrogels, click chemistry-based hydrogels, and supramolecular hydrogels. For each typical hydrogel, its preparation, structure, and mechanical performance are introduced in detail. At the end of this article, the current challenges and future prospects of hydrogels based on natural polymers are discussed and it is pointed out that 3D printing may offer a new platform for the development of natural polymer-based hydrogels.