Baghdadite Ceramics Prevent Senescence in Human Osteoblasts and Promote Bone Regeneration in Aged Rats,ACS Biomaterials Science & Engineering

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Baghdadite Ceramics Prevent Senescence in Human Osteoblasts and Promote Bone Regeneration in Aged Rats
ACS Biomaterials Science & Engineering ( IF 5.4 ) Pub Date : 2020-11-25 , DOI: 10.1021/acsbiomaterials.0c01120
ZuFu Lu _{1,

2} , WenJie Zhang _{3,

4,

5} , Young Jung No _{1,

2} , Yuezhi Lu _{3,

4,

5} , Seyed Mohammad Mirkhalaf Valashani _{1,

2} , Paul Rollet _{1,

2} , Liting Jiang _{3,

4,

5} , Yogambha Ramaswamy _{1,

2} , Colin R. Dunstan _{1,

2} , XinQuan Jiang _{3,

4,

5} , Hala Zreiqat _{1,

2}

Affiliation

Bone fractures and critical-sized bone defects present significant health threats for the elderly who have limited capacity for regeneration due to the presence of functionally compromised senescent cells. A wide range of synthetic materials has been developed to promote the regeneration of critical-sized bone defects, but it is largely unknown if a synthetic biomaterial (scaffold) can modulate cellular senescence and improve bone regeneration in aged scenarios. The current study investigates the interaction of Baghdadite (Ca₃ZrSi₂O₉) ceramic scaffolds with senescent human primary osteoblast-like cells (HOBs) and its bone regeneration capacity in aged rats. A senescent HOB model was established by repeatedly passaging HOBs till passage 7 (P7). Compared to the clinically used hydroxyapatite/tricalcium phosphate (HA/TCP), Baghdadite prevented senescence induction in P7 HOBs and markedly negated the paracrine effect of P7 HOB secretomes that mediated the up-regulations of cellular senescence-associated gene expression levels in P2 HOBs. We further demonstrated that conditioned media extracted from Baghdadite corrected the dysfunctional mitochondria in P7 HOBs. In vivo, the bone regeneration capacity was enhanced when 3D printed Baghdadite scaffolds were implanted in a calvaria critical-sized bone defect model in both young and aged rats compared to HA/TCP scaffolds, but a better effect was observed in aged rats than in young rats. This study suggests that Baghdadite ceramic represents a novel and promising biomaterial approach to promote bone regeneration capacity in the elderly by providing an anti-senescent microenvironment.

中文翻译：

Baghdadite陶瓷可防止人类成骨细胞衰老并促进老年大鼠的骨骼再生

对于由于功能受损的衰老细胞而导致再生能力有限的老年人，骨骨折和临界大小的骨缺损构成了严重的健康威胁。已经开发了各种各样的合成材料来促进临界大小的骨缺损的再生，但是，在未来的情况下，合成生物材料（支架）是否能够调节细胞衰老并改善骨骼的再生，在很大程度上是未知的。当前的研究调查了Baghdadite（Ca ₃ ZrSi ₂ O ₉）具有衰老的人类原代成骨细胞样细胞（HOB）的陶瓷支架及其在老年大鼠中的骨再生能力。通过反复传代HOB直到第7代（P7），建立了衰老的HOB模型。与临床上使用的羟基磷灰石/磷酸三钙（HA / TCP）相比，巴格达特阻止了P7 HOB的衰老诱导，并显着消除了P7 HOB分泌蛋白组的旁分泌作用，后者介导了P2 HOBs中与细胞衰老相关的基因表达水平的上调。我们进一步证明，从巴格达提取的条件培养基可以纠正P7 HOB中功能异常的线粒体。体内与HA / TCP支架相比，在年轻和老年大鼠中将3D打印的Baghdadite支架植入颅骨临界大小的骨缺损模型中时，骨骼的再生能力得到增强，但是在老年大鼠中观察到的效果要比年轻大鼠好。这项研究表明，巴格达陶瓷代表了一种新颖而有前途的生物材料方法，可通过提供抗衰老的微环境来促进老年人的骨再生能力。

更新日期：2020-12-14

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