Indian Institute of Technology , Rubber Technology Centre, Kharagpur 721302, India.
Sanjay Gandhi Post Graduate Institute of Medical Science , Department of Medical Genetics, Lucknow 226014, Uttar Pradesh India.
ACS Appl Mater Interfaces. 2016 Feb 17;8(6):4086-100. doi: 10.1021/acsami.5b11723. Epub 2016 Feb 4.
Guided bone regeneration (GBR) scaffolds are futile in many clinical applications due to infection problems. In this work, we fabricated GBR with an anti-infective scaffold by ornamenting 2D single crystalline bismuth-doped nanohydroxyapatite (Bi-nHA) rods onto segmented polyurethane (SPU). Bi-nHA with high aspect ratio was prepared without any templates. Subsequently, it was introduced into an unprecedented synthesized SPU matrix based on dual soft segments (PCL-b-PDMS) of poly(ε-caprolactone) (PCL) and poly(dimethylsiloxane) (PDMS), by an in situ technique followed by electrospinning to fabricate scaffolds. For comparison, undoped pristine nHA rods were also ornamented into it. The enzymatic ring-opening polymerization technique was adapted to synthesize soft segments of PCL-b-PDMS copolymers of SPU. Structure elucidation of the synthesized polymers is done by nuclear magnetic resonance spectroscopy. Sparingly, Bi-nHA ornamented scaffolds exhibit tremendous improvement (155%) in the mechanical properties with excellent antimicrobial activity against various human pathogens. After confirmation of high osteoconductivity, improved biodegradation, and excellent biocompatibility against osteoblast cells (in vitro), the scaffolds were implanted in rabbits by subcutaneous and intraosseous (tibial) sites. Various histological sections reveal the signatures of early cartilage formation, endochondral ossification, and rapid bone healing at 4 weeks of the critical defects filled with ornamented scaffold compared to SPU scaffold. This implies osteogenic potential and ability to provide an adequate biomimetic microenvironment for mineralization for GBR of the scaffolds. Organ toxicity studies further confirm that no tissue architecture abnormalities were observed in hepatic, cardiac, and renal tissue sections. This finding manifests the feasibility of fabricating a mechanically adequate nanofibrous SPU scaffold by a biomimetic strategy and the advantages of Bi-nHA ornamentation in promoting osteoblast phenotype progression with microbial protection (on-demand) for GBR applications.
在许多临床应用中，由于感染问题，引导骨再生（GBR）支架变得毫无用处。在这项工作中，我们通过在分段式聚氨酯（SPU）上装饰二维单晶掺铋纳米羟基磷灰石（Bi-nHA）棒来制造具有抗感染支架的 GBR。Bi-nHA 具有高纵横比，无需任何模板即可制备。随后，它通过原位技术引入到基于聚（ε-己内酯）（PCL）和聚二甲基硅氧烷（PDMS）的双软段（PCL-b-PDMS）的前所未有的合成 SPU 基质中，然后通过静电纺丝制造支架。为了进行比较，还将未掺杂的原始 nHA 棒装饰在其中。采用酶开环聚合技术合成 SPU 的软段 PCL-b-PDMS 共聚物。通过核磁共振波谱对合成聚合物的结构进行了阐明。Bi-nHA 装饰支架的机械性能大大提高（提高了 155％），并且对各种人类病原体具有出色的抗菌活性。在确认高骨传导性、改善的生物降解性以及对成骨细胞（体外）的良好生物相容性之后，将支架通过皮下和骨内（胫骨）部位植入兔子体内。与 SPU 支架相比，在 4 周的临界缺陷中，各种组织切片显示出早期软骨形成、软骨内骨化和快速骨愈合的特征，这些特征是用装饰支架填充的。这意味着支架具有成骨潜力，并能够为 GBR 提供足够的仿生微环境以进行矿化。器官毒性研究进一步证实，在肝、心和肾组织切片中未观察到组织结构异常。这一发现证明了通过仿生策略制造机械性能足够的纳米纤维 SPU 支架的可行性，以及 Bi-nHA 装饰在促进成骨细胞表型进展和微生物保护（按需）方面的优势，用于 GBR 应用。
