Biomimetic Bone for Load-Bearing Bioresorbable Nanostructured Bone Substitutes
Abstract
Topic Area: Nanomaterials for Bone Regeneration. Critical Problem: Although technological advances and better armor has reduced the overall number of injuries on the battlefield, the incidence of injuries to the head, jaw, and facial bones of Soldiers has been rising due to improvised explosive devices. These injuries can be both physically and emotionally devastating. Bone fractures (of all types) are also the highest cause of hospitalization for non-deployed Servicemen/women at the homeland, and are a significant problem for our Veterans. Bone is a living tissue that can repair small fractures; however, critical-sized defects require a scaffold for cells to rebuild bone. The current gold standard for bone repair is the patient s own bone (autograft), which is often taken from the iliac crest (the large hipbone) and crushed with a mix of bone marrow. An autograft, however, requires two surgical sites and can cause considerable pain in the hip where the bone was harvested. The amount of bone that can be taken is also limited, so reconstructive surgery often has to be augmented with either cadaver bone (allograft) or a synthetic material that is safe to use in the body. Cadaver bone has to be cleansed very well to avoid issues of disease transmission, but it then no longer contains the bioactive ingredients found in natural bone. Synthetic bone substitutes are being developed, often with the approach of making them biodegradable in order to have the synthetic material be replaced by bone. The central problem with this approach is that the rate of bone ingrowth needs to match the implant s degradation rate, the latter of which is a chemical process that is variable among patient populations and even different locations in the body. Synthetic materials are also not bioactive, so a recent approach is to add bioactive ingredients, such as growth factors, which stimulate the patient s stem cells to change into the types of cells that will form bone. These growth factors are very potent, and sometimes too much so, where if they leach out of the wound area, they stimulate bone to grow in the wrong place or even promote cancerous tumor formation. They are also unstable, making transport to military hospitals (or storage) very expensive and unfeasible at the battlefront. Innovative Solution: We propose to develop a synthetic material that has a similar composition and structure as bone so that it can be remodeled by the same cellular processes that are constantly remodeling our bones throughout our lives. This occurs through a multicellular bone remodeling unit (BRU), where osteoclast cells resorb old bone, which are closely followed by osteoblast cells, which lay down new bone. These two cell types (along with cells that form vasculature) work together in a synchronized fashion so that only a small channel is dug out of the old bone as it is immediately being replaced by new bone. We propose to fabricate a mineralized collagen scaffold with a nanostructure that "looks" like bone to the osteoclast cells, such that the cells recognize it as being bone-like and trigger the substitute to be remodeled by the concerted action of the BRU. This could enable the "biomimetic bone" substitute to maintain its load-bearing capacity throughout the remodeling process, as is the case for natural bone. Our approach to triggering this BRU is to use certain proteins, or chemical groups found on these proteins, that have been found to trigger the activation of osteoclasts. Based on observations that these osteoclasts release exosomes (vesicles) containing clastokines, which are signals that stimulate osteoblast cells, we hypothesize that these exosomes will recruit the appropriate cells to assemble into a BRU, thereby triggering remodeling of the implant via the natural pathway. Applicability: To date, there is no regenerative bone substitute that can maintain its load-bearing capacity as it is remodeled. Even autograft tis
Document Details
- Document Type
- DoD Grant Award
- Publication Date
- Aug 07, 2017
- Source ID
- W81XWH1710100
Entities
People
- Laurie A Gower
Organizations
- United States Army
- University of Florida