Sandor Maryellen, Leamy Patrick, Assan Pearl, Hoonjan Amardeep, Huang Li-Ting, Edwards Marianne, Zuo Wenqi, Li Hui, Xu Hui
LifeCell Corporation, an ACELITY Company, Bridgewater, NJ.
Eplasty. 2017 Jan 5;17:e1. eCollection 2017.
Benchtop methods were evaluated for preclinical inflammation/capsule formation correlation following implantation of human acellular dermal matrices. Dermal matrices were compared with native dermis for structure (histology, scanning electron microscopy), collagen solubility (hydroxyproline), enzymatic susceptibility (collagenase), and thermal stability (differential scanning calorimetry). Results were compared with implantation outcomes in a primate tissue expander model. Native dermis, electron beam-sterilized, and freeze-dried human acellular dermal matrices had equivalent morphology, acid-soluble collagen (60.5% ± 6.3%, 65.3% ± 3.2%, and 63.3% ± 2.4%, respectively), and collagenase resistance. Implant results showed minimal inflammation/matrix degradation, lack of capsule formation, insignificant elastic modulus change (57.65 ± 20.24 MPa out-of-package/44.84 ± 23.87 MPa in vivo), and low antibody induction (2- to 8-fold increase) for electron beam-sterilized matrix. Similar results for freeze-dried dermal matrix were previously observed. γ-Irradiated, γ-irradiated/freeze-dried, and ethanol-stored dermal matrices were statistically different from native dermis for acid-soluble collagen (82.4% ± 5.8%, 72.2% ± 6.2%, and 76.8% ± 5.0%, respectively) and collagenase digestion rate, indicating matrix damage. γ-Irradiated matrix-implanted animals demonstrated elevated inflammatory response, foreign body giant cells, capsule formation at the tissue expander junction, and robust matrix metalloproteinase-1 staining with significant elastic modulus decrease (37.43 ± 7.52 MPa out-of-package/19.58 ± 1.16 MPa in vivo). Antibody increase (32- to 128-fold) was observed 6 to 10 weeks following γ-irradiated matrix implantation. Ethanol-stored dermal matrix elicited an acute antibody response (4- to 128-fold increase, 2-4 weeks) and macrophage-concentrated synovial-like hyperplasia at the tissue expander junction, moderate matrix metalloproteinase-1 staining, and significant elastic modulus decrease (61.15 ± 9.12 MPa out-of-package/17.92 ± 4.02 MPa in vivo) by 10 weeks implantation. Demonstrated loss of collagen integrity in vitro may be predictive of inflammation/capsule formation in primate tissue expander models. These results may be further predictive of clinical observations.
在植入人脱细胞真皮基质后，对用于临床前炎症/包膜形成相关性研究的台式方法进行了评估。将真皮基质与天然真皮在结构（组织学、扫描电子显微镜）、胶原溶解性（羟脯氨酸）、酶敏感性（胶原酶）和热稳定性（差示扫描量热法）方面进行比较。将结果与灵长类组织扩张器模型中的植入结果进行比较。天然真皮、电子束灭菌的和冻干的人脱细胞真皮基质具有相似的形态、酸溶性胶原（分别为60.5%±6.3%、65.3%±3.2%和63.3%±2.4%）以及抗胶原酶能力。植入结果显示，电子束灭菌基质的炎症/基质降解最小、无包膜形成、弹性模量变化不显著（包装外57.65±20.24兆帕/体内44.84±23.87兆帕）以及抗体诱导水平低（增加2至8倍）。冻干真皮基质也观察到了类似结果。γ射线辐照的、γ射线辐照/冻干的和乙醇储存的真皮基质在酸溶性胶原（分别为82.4%±5.8%、72.2%±6.2%和76.8%±5.0%）和胶原酶消化率方面与天然真皮存在统计学差异，表明基质受到了损伤。植入γ射线辐照基质的动物表现出炎症反应增强、异物巨细胞、组织扩张器连接处形成包膜以及基质金属蛋白酶-1染色强烈，弹性模量显著降低（包装外37.43±7.52兆帕/体内19.58±1.16兆帕）。在植入γ射线辐照基质6至10周后观察到抗体增加（32至128倍）。乙醇储存的真皮基质引发急性抗体反应（4至128倍增加，2至4周），在组织扩张器连接处出现巨噬细胞聚集的滑膜样增生、基质金属蛋白酶-1染色中等，且在植入10周时弹性模量显著降低（包装外61.15±9.12兆帕/体内17.92±4.02兆帕）。体外显示的胶原完整性丧失可能预示着灵长类组织扩张器模型中的炎症/包膜形成。这些结果可能进一步预示临床观察结果。
