Bone tissue engineering

Bone is a rigid, highly vascularized connective tissue that forms our skeleton. It is a dynamic composite material that is constantly being resorbed, redeposited, and remodeled to accommodate the mechanical and biological demands on the body. While bone has a remarkable innate capacity for repair and regeneration, the process of healing fractures can take months or years, thereby disrupting function and quality of life for patients. Moreover, several mechanical, pathological, and nutritional factors can further impair the bone healing process and present major clinical challenges for treating and ensuring robust healing of bone injuries and defects. The current standard of treatment involves stabilizing fractures and defects with artificial implants and fixation devices, typically composed of metals or ceramic materials. Bone grafts such as autografts and allografts offer improved osteoconductivity, biocompatibility, and host-implant osseointegration compared to the traditional implant materials. However, these grafts are limited in their availability and consistency between patients and donors. Bone tissue engineering promises new, diverse, and versatile strategies for encouraging bone repair and regeneration. The core components of tissue engineering approaches are cells, growth factors, scaffolds, and biophysical signals. These components may be employed individually or in combination with one another. Cell therapies for bone tissue engineering include the injection or delivery of stem cells (e.g., mesenchymal stem cells) to the fracture site, in order to assist nearby cells in the bone repair process. Growth factors such as BMP-2, IGF, and VEGF can be administered or released into bone defects at supraphysiological doses to promote native or implanted cells to accelerate bone repair. Bone tissue engineering scaffolds are often polymeric or ceramic materials which provide a framework for bone healing and can harbor cells at the defect site. The mechanical, chemical, topographical, and degradative properties of scaffolds can be engineered to encourage cell attachment, proliferation, and differentiation or perform controlled growth factor delivery. In addition, advances in scaffold fabrication techniques, such as 3D printing, have made the design of patient-specific scaffolds more feasible. Beyond the use of cells, growth factors, and scaffolds in bone tissue engineering, new approaches have recently been developed which utilize physical or mechanical stimulation to facilitate bone repair and regeneration. Bone is one of the several musculoskeletal tissues that are capable of adapting and responding to mechanical signals. Numerous studies have evaluated the in vitro and in vivo effects of several kinds of mechanical stimulation on bone, including cyclic tensile and compressive strain, pulsatile and oscillatory fluid flow, and low-intensity pulsed ultrasound. Variations in the intensity, frequency, and duration of these stimuli can elicit different cellular responses related to osteogenesis, bone matrix deposition, and mineralization. In these stimuli-based tissue engineering approaches, stem cells are implanted in nontraditional scaffolds, such as soft, deformable, biopolymer hydrogels, through which mechanical forces can propagate and be transmitted to cells. Overall, tissue engineering provides new strategies for enhancing the repair and regeneration of bone, which may translate to improved clinical outcomes for patients suffering from bone fractures and defects.