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Bone formation is a complex process that requires concerted function of multiple growth factors. For this, it is essential to design a delivery system with the ability to load multiple growth factors in order to mimic the natural microenvironment for bone tissue formation. However, the short half-lives of growth factors, their relatively large size, slow tissue penetration, and high toxicity suggest that conventional routes of administration are unlikely to be effective. Therefore, it seems that using multiple bioactive factors in different delivery systems can develop new strategies for improving bone tissue regeneration. Combination of these factors along with biomaterials that permit tunable release profiles would help to achieve truly spatiotemporal regulation during delivery. This review summarizes the various dual-control release systems that are used for bone tissue engineering., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Regeneration of large bone defects is challenging in the next few years because the age of the population is growing. Bone grafting as a gold standard of bone repairing is limited as a result of many disadvantages. In recent years, many novel materials and processing methods have been introduced to construct the native bone extracellular matrix (ECM) and restore the functions of degenerated bone. Silk fibroin (SF) as a natural polymer, has established a good reputation for bone tissue engineering applications due to its many unique properties, including exceptional biocompatibility, biodegradability, mechanical behavior, and ease of processability. In this review, recent advances in the design and application of SF-based scaffolds for bone regeneration are discussed., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Thermosensitive nanoparticles with phase transition abilities have been considered as suitable materials in biomedical fields, especially drug delivery systems. Moreover, electroactive injectable hydrogels supporting bone regeneration of the elderly will highly be desired in bone tissue engineering applications. Herein, thermosensitive nanoparticles were fabricated using chitosan/poly(N-isopropyl acrylamide) for simvastatin acid delivery. The nanoparticles were incorporated into electroactive injectable hydrogels based on aniline pentamer/silk fibroin/polyacrylamide containing vitamin C. The nanoparticles had thermosensitive properties as simvastatin acid had higher release rates at 37 than 23 °C without significant burst release. The hydrogels also revealed an appropriate gelation time, stable mechanical and rheological characteristics, high water absorbency, and proper biodegradability. In vitro studies indicated that the hydrogel was biocompatible and nontoxic, especially those containing drugs. Implantation of the hydrogels containing both simvastatin acid and vitamin C into the critical calvarial bone defect of the aged rat also demonstrated significant enhancement of bone healing after 4 and 8 weeks post-implantation. We found that the electroactive injectable hydrogels containing thermosensitive nanoparticles exhibited great potential for treating bone defects in the elderly rats [ABSTRACT FROM AUTHOR]

Despite the progress in antibiotic treatment, it is still challenging to promote bone regeneration in the case of chronic bone infection. Here, we synthesized composite hydrogels containing silk fibroin/halloysite nanotubes loaded with vancomycin. The hydrogel possessed 79.32% porosity, acceptable cell attachment, and biocompatibility. The release kinetics of vancomycin from halloysite and halloysite embedded in hydrogel were 60% and 32.5% over 23 days, respectively. Disk diffusion also showed an appropriate antibacterial activity over 10 days. Alkaline phosphatase and Alizarin red staining proved osteoconductivity of the scaffold. Totally, the data showed that composite hydrogel can be considered for treatment of bone infection. [ABSTRACT FROM AUTHOR]

[Display omitted] • Reviewed and classified green biomaterials applied for bone tissue engineering. • Discussed additive manufacturing (printing) techniques for bone implantation. • Reviewed bioprinting techniques for bone repair with bio-ceramics and biopolymers. • Classified 3D, 4D, 5D, and 6D bioprinting techniques for bone repair/regeneration. • Classified bone fracture, healing and state-of-the-art features of bone repair. Despite exceptional self-regeneration properties of bone, severe injuries often require additional surgical intervention such as using artificial bone constructs. These structures need to meet structural and performance requirements. Moreover, when implanted, the rate and the mechanism of erosion and fracture of bone constructs should be optimized for stimulating the regeneration of defected bone and, more critically, providing support in the interim. Technological development in the fields of imaging and additive manufacturing revolutionized manufacturing personalized implants with characteristics matching the requirements of target injuries. From biomaterials point of view, greener and more sustainable biomaterials from renewable resources are on demand for bone regeneration; moreover, bone repair should meed engineering features like mechanical and load-bearing properties. Currently, potential processing methods are not limited to 3D printing, but include 4D and 5D printers by changing the time, dimension, and rotational degrees of freedom of printing machines. Several innovative processes and techniques enabled the application of metals, their alloys, ceramics, and polymers, providing an extremely wide spectrum of possibilities for designing bone implant. Herein, the critical aspects of biomaterials applied in bone tissue engineering, their application in bone repair and regeneration are summarized, and novel directions in bone tissue engineering based on green biomaterials are proposed for future developments. Eventually, the latest advances in the application of green biomaterials in clinics are outlined. [ABSTRACT FROM AUTHOR]