Tissue compatibility of two biodegradable tubular scaffolds implanted adjacent to skin or buccal mucosa in mice

Tissue compatibility of two biodegradable tubular scaffolds implanted adjacent to skin or buccal mucosa in mice
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DOI:
10.1089/107632702760240562
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发表时间:
2002-08-01
期刊:
影响因子:
--
通讯作者:
Baum, BJ
Baum, BJ
中科院分区:
生物2区
文献类型:
--
作者:
Aframian, DJ;Redman, RS;Baum, BJ

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头颈部癌症的放射治疗导致唾液腺实质明显丧失,导致唾液分泌物严重减少。目前,这些患者还没有令人满意的治疗方法。为了解决这个问题,我们正在利用组织工程学和基因转移原理来开发一种口腔植入的人工液体分泌装置。在目前的研究中,我们检查了两种可生物降解的基质的组织相容性,这两种基质可能有助于制造这样的装置。我们将聚L-乳酸(PLLA)、聚乙醇酸涂层聚乳酸(PGA/PLLA)或无支架的管状支架植入BALB/c小鼠背部皮肤下(早期毒性和生物相容性研究中广泛使用的位置),或靠近颊粘膜(功能和免疫学上完全不同的位置)。在移植后1、3、7、14和28天,对植入部位进行组织学检查,并通过常规临床化学和血液学分析评估全身反应。结缔组织中的炎症反应与使用的聚合物植入物的位置或类型相似。然而,假手术对照组的炎症反应较短,没有上皮样细胞和巨细胞。此外,与PGA/PLLA小管相比,PLLA小管的生物降解速度更慢。植入管状支架后,临床化学和血液学均无明显变化。这些结果表明,PLLA和PGA/PLLA支架在背部和口腔皮肤附近的组织反应基本相似。然而,这些研究也确定了一些潜在的重要问题,在开始该设备的任何临床应用之前必须解决这些问题。
Radiation therapy for cancer in the head and neck region leads to a marked loss of salivary gland parenchyma, resulting in a severe reduction of salivary secretions. Currently, there is no satisfactory treatment for these patients. To address this problem, we are using both tissue engineering and gene transfer principles to develop an orally implantable, artificial fluid-secreting device. In the present study, we examined the tissue compatibility of two biodegradable substrata potentially useful in fabricating such a device. We implanted in Balb/c mice tubular scaffolds of poly-L-lactic acid (PLLA), poly-glycolic acid coated with PLLA (PGA/PLLA), or nothing (sham-operated controls) either beneath the skin on the back, a site widely used in earlier toxicity and biocompatibility studies, or adjacent to the buccal mucosa, a site quite different functionally and immunologically. At 1, 3, 7, 14, and 28 days postimplantation, implant sites were examined histologically, and systemic responses were assessed by conventional clinical chemistry and hematology analyses. Inflammatory responses in the connective tissue were similar regardless of site or type of polymer implant used. However, inflammatory reactions were shorter and without epithelioid and giant cells in sham-operated controls. Also, biodegradation proceeded more slowly with the PLLA tubules than with the PGA/PLLA tubules. No significant changes in clinical chemistry and hematology were seen due to the implantation of tubular scaffolds. These results indicate that the tissue responses to PLLA and PGA/PLLA scaffolds are generally similar in areas subjacent to skin in the back and oral cavity. However, these studies also identified several potentially significant concerns that must be addressed prior to initiating any clinical applications of this device.