Emerging zero-dimensional to four-dimensional biomaterials for bone regeneration

Abstract

Bone is one of the most sophisticated and dynamic tissues in the human body, and is characterized by its remarkable potential for regeneration. In most cases, bone has the capacity to be restored to its original form with homeostatic functionality after injury without any remaining scarring. Throughout the fascinating processes of bone regeneration, a plethora of cell lineages and signaling molecules, together with the extracellular matrix, are precisely regulated at multiple length and time scales. However, conditions, such as delayed unions (or nonunion) and critical-sized bone defects, represent thorny challenges for orthopedic surgeons. During recent decades, a variety of novel biomaterials have been designed to mimic the organic and inorganic structure of the bone microenvironment, which have tremendously promoted and accelerated bone healing throughout different stages of bone regeneration. Advances in tissue engineering endowed bone scaffolds with phenomenal osteoconductivity, osteoinductivity, vascularization and neurotization effects as well as alluring properties, such as antibacterial effects. According to the dimensional structure and functional mechanism, these biomaterials are categorized as zero-dimensional, one-dimensional, two-dimensional, three-dimensional, and four-dimensional biomaterials. In this review, we comprehensively summarized the astounding advances in emerging biomaterials for bone regeneration by categorizing them as zero-dimensional to four-dimensional biomaterials, which were further elucidated by typical examples. Hopefully, this review will provide some inspiration for the future design of biomaterials for bone tissue engineering. Graphical abstract

Effects of Scaffold Shape on Bone Regeneration: Tiny Shape Differences Affect the Entire System

“…To improve the osteogenesis ability of scaffolds, previous studies mainly focused on the effects of raw material composition, substituted or doped ions, pore characteristics, and incorporation of growth factors, polysaccharides, stem cells, and extracellular vesicles. ,− However, the effects of scaffold shape on bone regeneration remained unclear. To date, the shape of granular scaffolds has not been considered; granular scaffolds are often manufactured by smashing the bulk material, producing irregular-shaped granules.…”

Phytochemical Compounds Involved in the Bone Regeneration Process and Their Innovative Administration: A Systematic Review

“…During many decades, a wide range of biomaterials have been developed to address the bone defects promoting the bone regeneration through various mechanisms such as: mechanical support, osteoconduction, osteoinduction, vascularization, neurotization, antibacterial effect etc. [34]. Primarily, the autologous bone grafts were considered the "gold standard" material for bone defects, but due to some disadvantages (limited quantity, long surgical procedures, and morbidity) they have been replaced by synthetic bone graft, therefore a plethora of emerging biomaterials have been designed possessing specific advantageous characteristics [35].…”

Biomaterial-based strategy for bone tumor therapy and bone defect regeneration: An innovative application option

“…It can provide active sites that support cell differentiation, growth, and proliferation. However, the cytotoxicity of graphene and its derivatives has always been problematic (Fang et al, 2022).…”

“…With the development of biomaterial science, inorganic nanoparticles have also made their way into therapeutics through the use of nanotechnology (Fang et al, 2022). Metal nanoparticles such as Fe and Cu, which have been incorporated into scaffolds, have shown potential in promoting the proliferation and differentiation of mesenchymal stem cells (MSCs) in animal models (Dang et al, 2018;Lu et al, 2018;Ma et al, 2018).…”

“…Hydrogels possess good biocompatibility, biodegradability, injectability, and the ability to load growth factors, meaning they have the potential to repair bone defects (Fang et al, 2022). Some new injectable hydrogels prepared through chemical reactions have been applied to bone tumor treatment.…”