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含有细胞外基质颗粒和生长因子的胶体凝胶用于大鼠临界尺寸颅骨缺损的骨再生

Colloidal Gels with Extracellular Matrix Particles and Growth Factors for Bone Regeneration in Critical Size Rat Calvarial Defects.

作者信息

Townsend Jakob M, Dennis S Connor, Whitlow Jonathan, Feng Yi, Wang Jinxi, Andrews Brian, Nudo Randolph J, Detamore Michael S, Berkland Cory J

机构信息

Stephenson School of Biomedical Engineering, University of Oklahoma, Norman, Oklahoma, 73019, USA.

Bioengineering Program, University of Kansas, Lawrence, Kansas, 66047, USA.

出版信息

AAPS J. 2017 May;19(3):703-711. doi: 10.1208/s12248-017-0045-0. Epub 2017 Jan 30.

Abstract

Colloidal gels encapsulating natural materials and exhibiting paste-like properties for placement are promising for filling complex geometries in craniofacial bone regeneration applications. Colloidal materials have demonstrated modest clinical outcomes as bone substitutes in orthopedic applications, but limited success in craniofacial applications. As such, development of a novel colloidal gel will fill a void in commercially available products for use in craniofacial reconstruction. One likely application for this technology is cranial reconstruction. Currently, traumatic brain injury (TBI) is often treated with a hemi-craniectomy, a procedure in which half the cranium is removed to allow the injured brain to swell and herniate beyond the enclosed cranial vault. The use of colloidal gels would allow for the design of a pliable material capable of expansion during brain swelling and facilitate cranial bone regeneration alleviating the need for a second surgery to replace the previously removed hemi-cranium. In the current study, colloidal nanoparticles of hydroxyapatite (HAp), demineralized bone matrix (DBM), and decellularized cartilage (DCC) were combined with hyaluronic acid (HA) to form colloidal gels with desirable rheological properties ([Formula: see text] ≥ 100 Pa). BMP-2 and VEGF growth factors were included to assess extracellular matrix (ECM) contribution of DBM and DCC. The HA-HAp (BMP-2) and HA-HAp-DCC group had 89 and 82% higher bone regeneration compared to the sham group, respectively (p < 0.01). Material retention issues observed may be alleviated by implementing chemical crosslinking. Overall, DCC may be a promising material for bone regeneration in general, and colloidal gels may hold significant potential in craniofacial applications.

摘要

包裹天然材料并具有可用于填充的糊状特性的胶体凝胶,在颅面骨再生应用中填充复杂几何形状方面很有前景。胶体材料在骨科应用中作为骨替代物已显示出一定的临床效果,但在颅面应用中取得的成功有限。因此,开发一种新型胶体凝胶将填补用于颅面重建的市售产品的空白。该技术的一个可能应用是颅骨重建。目前,创伤性脑损伤(TBI)通常采用半颅骨切除术进行治疗,该手术是切除一半颅骨,以使受伤的大脑肿胀并疝出封闭的颅腔。使用胶体凝胶将允许设计一种柔韧的材料,能够在脑肿胀期间膨胀,并促进颅骨再生,从而无需进行二次手术来替换先前切除的半颅骨。在当前的研究中,将羟基磷灰石(HAp)、脱矿骨基质(DBM)和脱细胞软骨(DCC)的胶体纳米颗粒与透明质酸(HA)结合,形成具有理想流变学特性([公式:见正文]≥100 Pa)的胶体凝胶。加入骨形态发生蛋白-2(BMP-2)和血管内皮生长因子(VEGF)以评估DBM和DCC对细胞外基质(ECM)的贡献。与假手术组相比,HA-HAp(BMP-2)组和HA-HAp-DCC组的骨再生分别高出89%和82%(p<0.01)。通过实施化学交联可能会缓解观察到的材料保留问题。总体而言,DCC一般可能是一种有前途的骨再生材料,而胶体凝胶在颅面应用中可能具有巨大潜力。

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