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

3D 打印功能石墨烯材料 (FGM) 作为骨再生的本征感应支架

• 批准号: 10259656
• 负责人: Stefanie Arlene Sydlik
• 金额: $ 19.17万
• 依托单位: CARNEGIE-MELLON UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2020
• 资助国家: 美国
• 起止时间: 2020-09-09 至 2023-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/10259656
• 关键词: 3D Print; Address; Affect; Alkaline Phosphatase; Area; Autologous; Biocompatible Materials; Biological; Biomimetics; Bone Injury; Bone Regeneration; Calvaria; Cells; Cephalic; Chemicals; Chemistry; Clinical; Couples; Crosslinker; Custom; Defect; Deformity; Degradation Pathway; Development; Dimensions; Effectiveness; Environment; Evaluation; Excision; Funding; Future; Generations; Graft Rejection; Human; Hydroxyapatites; Immune; Implant; In Vitro; Infection; Infiltration; Instruction; Ions; Irrigation; Mechanics; Mesenchymal Stem Cells; Methods; Modeling; Monitor; Morbidity - disease rate; Mus; Natural graphite; Nature; Operative Surgical Procedures; Orthopedics; Osteogenesis; Oxides; Oxygen; Pain; Pathway interactions; Patients; Polymers; Polyphosphates; Positioning Attribute; Powder dose form; Predisposition; Printing; Procedures; Property; Prosthesis; Prosthesis Implantation; Reaction; Regenerative response; Residual state; Reverse Transcriptase Polymerase Chain Reaction; Safety; Site; Surface; Surgeon; Suspensions; Techniques; Technology; Testing; Therapeutic; Tissue Donors; Tissue Transplantation; Tissues; Titanium; Transplantation; Traumatic injury; United States; Vertebral column; Water; aged; aqueous; automobile accident; battlefield injury; bone; bone quality; calcium phosphate; chemokine; controlled release; cytokine; graphene; healing; histological stains; implant material; improved; in vivo; in vivo evaluation; inorganic phosphate; intraperitoneal; laurencin; macrophage; mechanical properties; melting; monocyte; mouse model; novel; osteogenic; replacement tissue; scaffold; stem cell differentiation; traumatic event; tumor; uptake

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.

摘要 严重的骨损伤可能是由于创伤性事件，如车祸或战场受伤， 在美国，每年有数百万的病人接受手术，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可行的。 用于大面积缺损的治疗。这些手术受到缺乏供体组织的限制， 供体部位发病率、移植物排斥的可能性、感染易感性和移植的可行性。非 可再吸收的材料，例如钛，仍然作为永久性植入材料， 用于与天然组织整合。我们提出了一类新的3D打印石墨烯支架，以模拟 骨的复杂性，并诱导天然再生反应。 功能性石墨烯材料（FGM）是一类新型的潜在支架材料，其提供可调节的功能， 机械性能、可降解性和表面化学，它们一起可用于控制生物活性。 Sydlik小组已经开发了几种新型的FGM，其在体外和体内固有地诱导成骨。 具体地说，我们已经表明，磷酸钙石墨烯（CaPG）释放生物有益的抗衡离子，Ca 2 + 和PO 43-在小鼠模型中自发诱导体内骨生成（PNAS，2019）。但 FGM作为生物材料的应用受到限制，这是由于对化学界面的控制不足和有限的 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， 填充大面积骨缺损的体积结构。3D打印在应对这一挑战方面具有独特的优势 因为支架可以定制打印以匹配患者的缺损部位。该提案旨在推进 将生物活性成骨CaPG植入指导性支架中， 再生