Bioplinting：在手术期间修复皮肤和骨骼

This work is clinically significant," said Ibrahim T. Ozbolat, Hartz Family Career Development Associate Professor of Engineering Science and Mechanics, Biomedical Engineering and Neurosurgery, Penn State. "Dealing with composite defects, fixing hard and soft tissues at once, is difficult. And for the craniofacial area, the results have to be esthetically pleasing."

Currently, fixing a hole in the skull involving both bone and soft组织requires using bone from another part of the patient's body or a cadaver. The bone must be covered by soft tissue with blood flow, also harvested from somewhere else, or the bone will die. Then surgeons need to repair the soft tissue and skin.

Ozbolat and his team used extrusionbioprintingand droplet bioprinting of mixtures of cells and carrier materials to print both bone and soft tissue. "There is no surgical method for repairing soft and hard tissue at once," said Ozbolat. "This is why we aimed to demonstrate a technology where we can reconstruct the whole defect—bone to epidermis—at once."

研究人员首先攻击了骨骼替代的问题，从实验室开始并移动到动物模型。他们需要可打印和无毒的东西，可以在头骨中修复5毫米孔。“硬组织油墨”由胶原，壳聚糖，纳米羟基磷灰石和其他化合物和间充质干细胞组成，在骨髓中发现的骨髓，软骨和骨髓脂肪中发现的多能细胞。

硬组织油墨在室温下挤出，但施加时加热到体温。这产生了胶原的物理交联和墨水的其他部分而没有任何化学变化或交联剂添加剂的必要性。

研究人员使用液滴印刷来产生比骨骼更薄的层的软组织。它们在交替层中使用胶原蛋白和纤维蛋白原，具有交联和生长增强化合物。包括表皮和真皮在内的每层皮肤不同，因此生物印刷的软组织层在组合物中不同。

在全厚度皮肤上修复6毫米孔的实验证明是成功的。一旦团队分开了解皮肤和骨骼，它们就会在相同的外科手术过程中进行修复。“这种方法是一个极具挑战性的过程，我们实际上花了很多时间找到了骨骼，皮肤和正确的生物印刷技术的合适材料，”奥塞尔特说。

After careful imaging to determine the geometry of the defect, the researchers laid down the bone layer. They then deposited a barrier layer mimicking the periosteum, a heavily vascularized tissue layer that surrounds the bone on the skull. "We needed the barrier to ensure that cells from the skin layers didn't migrate into the bone area and begin to grow there," said Ozbolat.

After laying down the barrier, the researchers printed the layers of dermis and then the epidermis. "It took less than 5 minutes for the bioprinter to lay down the bone layer and soft tissue," said Ozbolat.

The researchers performed more than 50 defect closures and achieved 100% closure of soft tissue in four weeks. The closure rate for bone was 80% in six weeks, but Ozbolat noted that even with harvested bone replacement, bone closure usually does not reach 100% in six weeks.

根据ozbolat，对骨的血流尤为重要，并且包含血管化化合物是下一步。研究人员还希望将该研究转化为人类应用，并继续与Penn State Hershey Medical Centre的神经外科医生，颅骨外科医生和整形外科医生一起使用。它们在较大的动物上操作较大的生物印刷设备。

研究人员报告了他们的结果先进的功能材料。