3D printing functional graphenic materials (FGMs) as intrinsically inductive scaffolds for bone regeneration

摘要 严重的骨骼损伤可因创伤事件而发生，如车祸或战场伤害，以及 在美国，每年都有数以百万计的病人接受手术，通常是侵入性的和痛苦的 来矫正这些畸形。目前，自体组织移植或假体装置的植入是 用于治疗大面积缺损区。这些手术因缺乏供体组织而受到限制， 供体部位发病率、移植排斥反应的可能性、对感染的易感性以及移植的可行性。非- 可吸收材料，如钛，仍然是一种永久性的植入材料，缺乏重塑的能力。 用于与天然组织整合。我们提出了一类新的3D打印图形支架来模拟 骨骼的复杂性，并诱导天然的再生反应。 功能石墨材料(FGM)是一类新型的潜在支架材料，具有可调性 机械性能、可降解性和表面化学，这些都可以用来控制生物活性。 Sydlik团队已经开发出几种新型的功能梯度材料，这种材料在体外和体内都能诱导成骨。 具体地说，我们已经证明了磷酸钙石墨烯(CAPG)释放了具有生物教育意义的反离子，即钙离子。 和PO43-，自发地在小鼠模型中诱导体内成骨(PNAS，2019)。然而， 由于化学界面控制不充分，限制了功能梯度材料作为生物材料的应用 加工方法。因此，为了使这项技术可翻译，我们需要一种制造技术来创建 体积构造物，以填充较大的骨缺损。3D打印在应对这一挑战方面具有独特的定位 因为支架可以定制打印，以匹配患者的缺损处。这项建议旨在推进 生物活性成骨CAPG植入具有指导意义的支架，显著改善颅骨 再生。

Abstract Severe bone injury can occur due to traumatic events such as automobile accidents or battlefield injuries, and every year millions of patients in the United States undergo procedures, often invasive and painful, every year to correct these deformities. Currently, autologous tissue transplantation or implantation of prosthetic devices is used as a therapeutic treatment for large defect areas. These procedures are limited by a lack of donor tissue, donor site morbidity, potential for graft rejection, susceptibility to infection, and feasibility of transplantation. Non- resorbable materials, such as titanium, remain as a permanent implant material and lack the ability to remodeled for integration with native tissue. We propose a new class of 3D printed graphenic scaffold to mimic the complexity of bone and induce the native regenerative response. Functional graphenic materials (FGMs) are a novel class of potential scaffold material that offer tunable mechanical properties, degradability, and surface chemistry, which together can be used to control bioactivity. The Sydlik group has developed several novel FGMs that inherently induce osteogenesis in vitro and in vivo. Specifically, we have shown that calcium phosphate graphene (CaPG) releases bioinstructive counter ions, Ca2+ and PO43- , to spontaneously induces osteogenesis in vivo in a mouse model (PNAS, 2019). However, the application of FGMs as biomaterials is restricted due to insufficient control of the chemical interface and limited processing methods. Thus, to make this technology translatable, we need a fabrication technique that can create volumetric constructs to fill large bone defects. 3D printing is uniquely positioned to address this challenge because scaffolds can be custom printed to match the patients defect site. This proposal seeks to advance bioactive osteogenic CaPG into instructive scaffolds that achieve significantly improved cranial bone regeneration.