Evaluation of resorption and biocompatibility of collagen hemostats in the spinal epidural space.
BACKGROUND
Collagen hemostats have different characteristics depending on their properties and configuration. In vivo serial evaluation of local reactions because of placement of hemostats in the epidural space has not been reported.


OBJECTIVE
This study compared the resorption and biocompatibility of two types of collagen hemostats placed in the epidural space.


METHODS
This in vivo study used experimental animals to evaluate collagen hemostats that were placed in the epidural space.


METHODS
A ligamentum flavum resection model was created in Japanese white rabbits (n=65). A microfibrillar collagen hemostat (MCH group, n=5), cotton-type collagen hemostat (CCH group, n=5) that was chemically cross-linked, or no hemostat (control group, n=4) was placed in the spinal epidural space. For histologic evaluation, each group was euthanized 1, 2, 4, and 8 weeks postoperatively (PO), and hematoxylin-eosin and immunohistochemical (IHC) staining for inflammatory cytokines (tumor necrosis factor [TNF]-α, interleukin [IL]-6), cyclooxygenase (COX)-2, and macrophages (CD68) was performed. To evaluate exudate accumulation and the degree of inflammation in the epidural space, magnetic resonance imaging at 7.04 T was serially performed in each group (n=3) under anesthesia and sedation.


RESULTS
The collagen hemostats in both groups were reabsorbed at 4 weeks PO. In the MCH group, there was inflammatory cell infiltration and granuloma formation around the hemostat, TNF-α-positive cells were seen up to 1 week, and IL-6-, COX-2-, and CD68-positive cells were seen at all evaluation times. In the CCH group, no inflammatory cell infiltration around the hemostat was observed, and IHC staining showed no positive cells at 4 weeks PO and later. T2*-weighted MR images showed significantly higher mean signal intensity of the epidural space in the MCH group than in the CCH group but only at 1 week PO (p<.05).


CONCLUSIONS
Resorption of both hemostats was similar. In the MCH group, there was intense tissue inflammation around the hemostatic material, and MR images showed high signal intensity because of exudate accumulation in the epidural space. This indicated a strong foreign-body reaction to the MCH, thus demonstrating a difference in biocompatibility with the CCH.
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Kentaro
K
Mizuno
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan. Electronic address: tikeda@koto.kpu-m.ac.jp.
Takumi
T
Ikeda
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Kazuya
K
Ikoma
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Hidenobu
H
Ishibashi
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Hitoshi
H
Tonomura
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Masateru
M
Nagae
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Yuji
Y
Arai
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Hiroyoshi
H
Fujiwara
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Yasuo
Y
Mikami
Department of Orthopaedics, Graduate School of Medical Science, Kyoto Prefectural University of Medicine, 465 Kawaramachi-Hirokoji, Kamigyo-ku, Kyoto 602-8566, Japan.
Toshikazu
T
Kubo
D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D001672:Biocompatible Materials / Q000627:therapeutic use*; D003094:Collagen / Q000627:therapeutic use*; D051546:Cyclooxygenase 2 / Q000378:metabolism; D016207:Cytokines / Q000378:metabolism*; D004824:Epidural Space / Q000473:pathology / Q000601:surgery*; D006490:Hemostatics / Q000627:therapeutic use*; D007150:Immunohistochemistry; D007249:Inflammation / Q000473:pathology; D015850:Interleukin-6 / Q000378:metabolism; D017843:Ligamentum Flavum / Q000601:surgery*; D008264:Macrophages / Q000378:metabolism; D008279:Magnetic Resonance Imaging; D008422:Materials Testing; D011817:Rabbits; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000097382:CD68 Molecule
D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D001672:Biocompatible Materials; D003094:Collagen; D051546:Cyclooxygenase 2; D016207:Cytokines; D006490:Hemostatics; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C067980:CD68 antigen, human; D000097382:CD68 Molecule
Antigenicity; Biocompatibility; Collagen hemostat; Inflammation; Resorption; Spinal epidural space