Nikhil Aman, Gugjoo Mudasir B, Das Ankita, Ahmad Syed M, Kumar Ashok
Department of Biological Sciences and Bioengineering, Indian Institute of Technology Kanpur, Kanpur, U.P., 208016, India.
Division of Veterinary Clinical Complex, SKUAST-Kashmir, Srinagar, J&K, 190006, India.
Adv Healthc Mater. 2024 Dec;13(32):e2402619. doi: 10.1002/adhm.202402619. Epub 2024 Sep 30.
Critical-size bone trauma injuries present a significant clinical challenge because of the limited availability of autografts. In this study, a photocurable composite comprising of polycaprolactone, polypropylene fumarate, and nano-hydroxyapatite (nHAP) (P─P─H) is printed, which shows good osteoconduction in a rat model. A cryogel composed of gelatin-nHAP (GH) is developed to incorporate osteogenic components, specifically bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA), termed as GH+B+Z, which is investigated for osteoinductive property in a rat model. Further, a 3D-printed P─P─H scaffold impregnated with GH+B+Z is designed and implanted in a critical-size defect (25 × 10 × 5 mm) in goat tibia. After 4 months, the scaffold is well-integrated with adjacent native bone, with osteoinduction observed in the cryogel-filled region and osteoconduction over the printed scaffold. X-ray radiography and micro-CT analysis showed bone in-growth in the treatment group with 45 ± 1.4% bone volume/tissue volume (BV/TV), while the defect remained unhealed in the control group with BV/TV of 10.5 ± 0.5%. Histology showed significant cell infiltration and matrix deposition over the printed P─P─H scaffold and within the GH cryogel site in the treatment group. Immunohistochemical staining depicted significantly higher normalized collagen I intensity in the treatment group (34.45 ± 2.61%) compared to the control group (4.22 ± 0.78).
由于自体骨移植的可用性有限，临界尺寸的骨创伤损伤带来了重大的临床挑战。在本研究中，打印了一种由聚己内酯、聚富马酸丙二醇酯和纳米羟基磷灰石（nHAP）组成的光固化复合材料（P─P─H），其在大鼠模型中显示出良好的骨传导性。开发了一种由明胶 - nHAP（GH）组成的冷冻凝胶，以掺入成骨成分，特别是骨形态发生蛋白 - 2（BMP - 2）和唑来膦酸（ZA），称为GH + B + Z，并在大鼠模型中研究其骨诱导特性。此外，设计了一种浸渍有GH + B + Z的3D打印P─P─H支架，并将其植入山羊胫骨的临界尺寸缺损（25×10×5mm）中。4个月后，支架与相邻的天然骨良好整合，在冷冻凝胶填充区域观察到骨诱导，在打印的支架上观察到骨传导。X射线摄影和显微CT分析显示，治疗组骨向内生长，骨体积/组织体积（BV/TV）为45±1.4%，而对照组缺损仍未愈合，BV/TV为10.5±0.5%。组织学显示，治疗组在打印的P─P─H支架上和GH冷冻凝胶部位内有明显的细胞浸润和基质沉积。免疫组织化学染色显示，治疗组的归一化I型胶原蛋白强度（34.45±2.61%）明显高于对照组（4.22±0.78）。
