Research problem

Bone tissue owns an intrinsic regenerative capability to make up deformations but severe fractures interrupt this ability. Severe bone defects are conventionally managed and treated by allografts and autografts that still face several shortcomings such as high cost, donor limitation, donor site morbidity, and postoperative complications.

Approach

Bone is the complex and hierarchical tissue consisting of outer cortical and inner spongy bone and is composed of osteocytes, osteoblasts, and osteoclasts cells. Bone tissue has an intrinsic regenerative capability to make up deformations, but the healing of a severe bone defect involves the tedious and multistep process regulated by the interactions between biological and physiochemical factors, including growth factors, cells, biomechanical strength, and the extracellular matrix. The worldwide incidence of bone disorders has trended steeply upward and is expected to double by 2024, especially in populations where aging is coupled with increased obesity and poor physical activity. According to a study, every woman out of 4 and man out of 5 is affected by bone diseases. It has been reported that 60% of patients examined by knee arthroscopy exhibit bone defects and cartilage damage, whereas ~15% of people over 60 years old have some clinical symptoms of bone diseases. Additionally each year an estimated 1.5 million individuals suffer a fracture due to bone disease. Across the globe, an osteoporotic fracture is estimated to occur every 3 seconds.
Approximately 2.21 million procedures for bone regeneration including allograft and autologous bone are instigated per annum. The auto and allograft substitute market stands at 2.35 billion US$ in 2014, it was estimated at $3.3 billion in 2017 and is expected to surpass US$3.48 billion by the year 2023 presenting a huge expenditure to the national economy. In situ forming injectable hydrogels have recently achieved tremendous attention in bone remodeling, as they were considered to be the quality alternative to those applied after surgical intervention and can synergistically promote the healing of defective bones.
In our project, we stepped towards an approach to develop biomimetic polymer-based curcumin nanocrystals (Cur-NCs) for controlled and targeted delivery in bone defect models to increase the proliferation and remodeling of bone tissue. Moreover, these Cur-NCs will be loaded in the bioactive polysaccharides-based in situ injectable hydrogels. The incorporation of bioactive polymers will be selected based on structural similarity to the constituent of the ECM in bone tissue and mechanical strength. These biomimetic injectable hydrogels can potentially promote matrix deposition and provide a compassionate environment for osteocyte differentiation and proliferation. Besides, the osteocytes will also be encapsulated in the hydrogel system in vitro to evaluate the cell survival and cytotoxicity determination.