Advances in additive manufacturing of polycaprolactone based scaffolds for bone regeneration.

Critical sized bone defects are difficult to manage and currently available clinical/surgical strategies for treatment are not completely successful. Polycaprolactone (PCL) which is a biodegradable and biocompatible thermoplastic can be 3D printed using medical images into patient specific bone implants. The excellent mechanical properties and low immunogenicity of PCL makes it an ideal biomaterial candidate for 3D printing of bone implants. Though PCL suffers from the limitation of being bio-inert. Here we describe the use of PCL as a biomaterial for 3D printing for bone regeneration, and advances made in the field. The specific focus is on the different 3D printing techniques used for this purpose and various modification that can enhance bone regeneration following the development pathways. We further describe the effect of various scaffold characteristics on bone regeneration both in vitro and the translational assessment of these 3D printed PCL scaffolds in animal studies. The generated knowledge will help understand cell-material interactions of 3D printed PCL scaffolds, to further improve scaffold chemistry and design that can replicate bone developmental processes and can be translated clinically.

Tissue Engineering Strategies for Treating Avascular Necrosis of the Femoral Head.

Avascular necrosis (AVN) of the femoral head commonly leads to symptomatic osteoarthritis of the hip. In older patients, hip replacement is a viable option that restores the hip biomechanics and improves pain but in pediatric, adolescent, and young adult patients hip replacements impose significant activity limitations and the need for multiple revision surgeries with increasing risk of complication. Early detection of AVN requires a high level of suspicion as diagnostic techniques such as X-rays are not sensitive in the early stages of the disease. There are multiple etiologies that can lead to this disease. In the pediatric and adolescent population, trauma is a commonly recognized cause of AVN. The understanding of the pathophysiology of the disease is limited, adding to the challenge of devising a clinically effective treatment strategy. Surgical techniques to prevent progression of the disease and avoid total hip replacement include core decompression, vascular grafts, and use of bone-marrow derived stem cells with or without adjuncts, such as bisphosphonates and bone morphogenetic protein (BMP), all of which are partially effective only in the very early stages of the disease. Further, these strategies often only improve pain and range of motion in the short-term in some patients and do not predictably prevent progression of the disease. Tissue engineering strategies with the combined use of biomaterials, stem cells and growth factors offer a potential strategy to avoid metallic implants and surgery. Structural, bioactive biomaterial platforms could help in stabilizing the femoral head while inducing osteogenic differentiation to regenerate bone and provide angiogenic cues to concomitantly recover vasculature in the femoral head. Moreover, injectable systems that can be delivered using a minimal invasive procedure and provide mechanical support the collapsing femoral head could potentially alleviate the need for surgical interventions in the future. The present review describes the limitations of existing surgical methods and the recent advances in tissue engineering that are leading in the direction of a clinically effective, translational solution for AVN in future.