Department of Biomedical Materials Science, School of Dentistry, University of Mississippi Medical Center, 2500 N State St, Jackson, MS, 39216, USA.
Department of Anesthesiology, University of Mississippi Medical Center, 2500 N State St, Jackson, MS, 39216, USA.
Adv Healthc Mater. 2023 Mar;12(8):e2202477. doi: 10.1002/adhm.202202477. Epub 2022 Dec 21.
Critical-sized cranial bone defects fail to re-ossify and require the surgical intervention of cranioplasty. To achieve superior bone healing in such cases, a hydrogel consisting of an interpenetrating network of collagen and elastin-like polypeptide to encapsulate bone morphogenetic protein-2 (BMP-2), doxycycline, and 45S5 Bioglass is developed. This hydrogel has an appropriate elastic modulus of 39 ± 2.2 kPa to allow proper handling during implantation. The hydrogel promotes human adipose-derived stem attachment, proliferation, and differentiation toward the osteogenic lineage, including the deposition of hydroxyapatite particles embedded within a collagenous fibrillar structure after 21 days of in vitro culture. After eight weeks of implantation of the acellular hydrogel in a critical-sized rat cranial defect model, only a small quantity of various pro-inflammatory (< 20 pg mg ) and anti-inflammatory (< 10 pg mg ) factors in the adjacent cranial tissue is noticed, indicating the overall biocompatibility of the hydrogel. Scanning electron microscopy evidenced the presence of new fibrous extracellular matrix and mineral aggregates at the defect site, with calcium/phosphorus ratio of 0.5 and 2.0 by eight and twelve weeks, respectively. Microcomputed tomography (Micro-CT) and histological analyses showed formation of mature mineralized tissue that bridged with the surrounding bone. Taken together, the acellular composite hydrogel shows great promise for superior bone healing after cranioplasty.
临界尺寸的颅骨缺损无法重新骨化，需要颅骨修复术的外科干预。为了在这种情况下实现更好的骨愈合，开发了一种由胶原和弹性蛋白样多肽的互穿网络组成的水凝胶，以封装骨形态发生蛋白-2（BMP-2）、强力霉素和 45S5 生物玻璃。这种水凝胶具有适当的弹性模量 39 ± 2.2 kPa，以便在植入过程中进行适当的处理。水凝胶促进人脂肪源性干细胞附着、增殖和向成骨谱系分化，包括在体外培养 21 天后在胶原纤维状结构中嵌入羟基磷灰石颗粒的沉积。在临界尺寸大鼠颅骨缺损模型中植入非细胞水凝胶八周后，仅在相邻颅骨组织中注意到少量各种促炎（<20 pg mg）和抗炎（<10 pg mg）因子，表明水凝胶的整体生物相容性。扫描电子显微镜证明在缺陷部位存在新的纤维细胞外基质和矿物质聚集体，钙/磷比分别在 8 周和 12 周时为 0.5 和 2.0。微计算机断层扫描（Micro-CT）和组织学分析显示形成了成熟的矿化组织，与周围骨骼桥接。总之，非细胞复合水凝胶在颅骨修复后具有很好的促进骨愈合的前景。
