The Journal of Bone & Joint Surgery

The Journal of Bone & Joint Surgery, Volume 93, Issue 2

Scientific Articles | January 19, 2011

Reduction of Peritendinous Adhesions by Hydrogel Containing Biocompatible Phospholipid Polymer MPC for Tendon Repair

Noriyuki Ishiyama, MD¹; Toru Moro, MD¹; Takashi Ohe, MD¹; Toshiki Miura, MD¹; Kazuhiko Ishihara, PhD¹; Tomohiro Konno, PhD¹; Tadashi Ohyama, PhD²; Mizuna Kimura, PhD²; Masayuki Kyomoto, PhD¹; Taku Saito, MD¹; Kozo Nakamura, MD¹; Hiroshi Kawaguchi, MD, PhD¹

¹ Sensory & Motor System Medicine (N.I., T. Ohe, T. Miura, T.S., K.N., and H.K.), Science for Joint Reconstruction (T. Moro and M.K.), Department of Materials Engineering (K.I.), Department of Bioengineering (T. Konno), University of Tokyo, Hongo 7-3-1, Bunkyo-ku, Tokyo 113-8655, Japan. E-mail address for H. Kawaguchi: kawaguchi-ort@h.u-tokyo.ac.jp
² Central Research Laboratories, Kaken Pharmaceutical, Yamashina, Kyoto 607-8042, Japan

View Disclosures and Other Information

Disclosure: In support of their research for or preparation of this work, one or more of the authors received, in any one year, outside funding or grants in excess of $10,000 from a Health and Welfare Research Grant for Translational Research (H19-006) from the Japanese Ministry of Health, Labor, and Welfare. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity.

A commentary by Nikolaos Gougoulias, MD, PhD, and Nicola Maffulli, MD, MS, PhD, FRCS(Orth), is available at www.jbjs.org/commentary and is linked to the online version of this article.

Investigation performed at the University of Tokyo, Tokyo, Japan

J Bone Joint Surg Am, 2011 Jan 19;93(2):142-149. doi: 10.2106/JBJS.I.01634

A commentary by Nicola Maffulli, MD, MS, PhD, FRCS(Orth), is available here

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Abstract

Background:

Peritendinous adhesions are serious complications after surgical repair of tendons. As an anti-adhesion material, we focused on 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, our original biocompatible polymer, and prepared an aqueous solution of MPC-containing polymer called poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid) (PMBV), which can be formed into hydrogel properties by mixture with another aqueous polymer, poly(vinyl alcohol) (PVA). The objective of the present study was to examine the possible application of the MPC hydrogel for the reduction of peritendinous adhesions.

Methods:

The effects of the hydrogel on peritendinous adhesions and tendon healing were examined by means of histological and mechanical analyses in a rat Achilles tendon model and a rabbit flexor digitorum profundus tendon model. Cell migration and viability were examined with use of fibroblastic NIH3T3 cells cultured in a double chamber dish.

Results:

Among the concentrations examined, 2.5% and 5.0% PMBV formed hydrogel properties immediately after mixing with 2.5% PVA and maintained a honeycomb microstructure with nanometer-scaled pores for three weeks after implantation. In animal models, the hydrogel formed from 5.0% PMBV remained at the sutured site during the critical period up to three weeks and disappeared by six weeks. The MPC hydrogel reduced the peritendinous adhesions histologically and mechanically by >25% at three weeks, without impairing tendon healing as determined with mechanical analyses. In the cell culture, cell migration was reduced by the MPC hydrogel, although cell viability was unaffected, indicating physical prevention, rather than cytotoxicity, to be the anti-adhesion mechanism.

Conclusions:

The MPC hydrogel that was formed by a local injection and mixture of two aqueous solutions, 5.0% PMBV and 2.5% PVA, reduced peritendinous adhesions without impairing tendon healing. This effect may be due to its excellent biocompatibility without a foreign-body reaction and the formation of a microstructure that physically prevents passage of cells but allows cytokines and growth factors to pass for healing.

Clinical Relevance:

This nanotechnology could potentially improve the quality of surgical repair of tendon, especially the zone-II area of the digital flexor tendon.

Figures in this Article

Introduction

Healing of a severed tendon after surgical repair is achieved by tenocytes inside the tendon sheath with a sufficient supply of local cytokines and growth factors^1-4. In contrast, adhesions between the tendon and the surrounding tissues, the most serious complication of tendon repair, are caused by chemotaxis of extrinsic fibroblastic precursor cells^3-6. Hence, a mechanical barrier that blocks passage of the extrinsic cells but allows cytokines and growth factors to pass may be a useful material for tendon repair without peritendinous adhesions. Considering that the barrier should tightly cover the sutured tendon without foreign-body reactions, we have sought to develop bioinert aqueous solutions that are molded into hydrogel properties in situ immediately after injection.

For the material, we focused on 2-methacryloyloxyethyl phosphorylcholine (MPC) polymer, our original biocompatible polymer, whose side chain is composed of phosphorylcholine mimicking the neutral phospholipids of biomembranes. Because of its bioinert properties, MPC polymer has excellent anti-thrombogenicity and cytocompatibility without foreign-body reaction to endogenous cells or proteins^7-10. MPC polymer that has been grafted onto the surface of several medical devices has been shown to suppress biological reactions even when they are in contact with living organisms and is now clinically used on the surfaces of intravascular stents, soft contact lenses, and an artificial lung under the authorization of the United States Food and Drug Administration^11-14. As applied to orthopaedics, our preclinical joint simulator experiments and animal studies showed that surface grafting of MPC polymer on an ultra-high molecular weight polyethylene liner may extend the longevity of artificial joints by reduction of periprosthetic osteolysis as the MPC-grafted wear particles were biologically inert and did not cause subsequent bone resorptive responses^15-17.

The objective of the present study was to examine the possible application of a material containing MPC polymer for the reduction of peritendinous adhesions. We initially prepared an aqueous solution of MPC-containing biocompatible phospholipid polymer called poly(2-methacryloyloxyethyl phosphorylcholine-co-n-butyl methacrylate-co-p-vinylphenylboronic acid) (PMBV), which can be formed into a hydrogel by mixing with another aqueous solution of polymer poly(vinyl alcohol) (PVA)¹⁸, and determined the optimum concentration of the PMBV polymer. We then investigated the effects of local application of the MPC hydrogel on peritendinous adhesions and tendon healing with use of an animal model. Finally, we looked into the mechanism underlying the anti-adhesion effect of MPC hydrogel using cell culture systems.

Materials and Methods

Rat Achilles Tendon Model

All animal experiments were performed according to the protocol approved by the Animal Care and Use Committee of Central Research Laboratories of Kaken Pharmaceutical Corporation. To examine the effects of a local application of MPC hydrogel, we initially used the rat Achilles tendon model because the tendon size was optimal for biomechanical analyses. After the induction of general anesthesia with pentobarbiturate (50 g/kg body weight), the Achilles tendon of seven-week-old Slc:Wistar rats was exposed and cut with a scalpel 5 mm proximal to its calcaneal insertion. The Kessler stitch with 6-0 braided polyester and the continuous adaptation stitch with 8-0 nylon monofilament were used for circumferential epitenon repair¹⁹. The animals were randomly divided into three groups (with six animals per group); two groups were subjected to local injections of the MPC hydrogels formed from 2.5% PMBV and 5.0% PMBV, whereas the third group (the control group) received injections of distilled water. After skin closure, the leg was immobilized in a cast to limit movement of the talocrural joint. The rats were allowed unrestricted activity and received food and water ad libitum. After three weeks, the animals were killed and the peritendinous adhesions and tendon healing were compared with those in the control group.

Rabbit Flexor Digitorum Profundus Tendon Model

To confirm the effects of the MPC hydrogel formed from 5.0% PMBV, we used the rabbit flexor digitorum profundus tendon model with a flexor mechanism analogous to human digits²⁰. After the induction of general anesthesia with intramuscular injections of ketamine (33.3 mg/kg body weight) and xylazine (6.7 mg/kg body weight), the zone-II area of the flexor digitorum profundus tendon of the second and fourth toes of seventy-two ten-week-old Japanese white rabbits (Kitayama, Nagano, Japan) was released from the tendon sheath, divided, cut with the scalpel just distal to the chiasm and proximal to the vincula, and sutured with the Kessler stitch with 6-0 braided polyester and the continuous adaptation stitch with 8-0 nylon monofilament for circumferential epitenon repair²¹. The animals were then randomly divided into two groups (with twelve animals per group); one group was subjected to local applications of the MPC hydrogel formed from 5.0% PMBV, and the other group (the control group) received applications of distilled water. After skin closure, the operatively treated leg was immobilized in a cast to limit the movement of the interphalangeal joints. The animals were allowed unrestricted activity and received food and water ad libitum. After one, three, and six weeks, the animals were killed and the peritendinous adhesions and tendon healing were compared with those in the control group.

Macroscopic Evaluation

Before the animals were killed, the incision site was examined for signs of inflammation and to confirm wound-healing. To evaluate peritendinous adhesions, we counted the number of fibrous adhesions around the sutured tendon that required sharp dissection for release, as previously reported^22,23. This parameter was evaluated by a single observer who was blinded to the experimental group and the period after surgery.

Histological Evaluation

The second toes of the rabbits (n = 5 per group) were fixed in 4% paraformaldehyde buffered with phosphate-buffered saline (PBS), sectioned into 4-µm slices, and subjected to hematoxylin-eosin staining according to standard protocol. The peritendinous adhesion tissue formation, inflammatory reaction, and remainder of the MPC hydrogel at one, three, and six weeks were evaluated qualitatively by a single observer who was blinded to the experimental group and the period after surgery. To categorize the severity of peritendinous adhesions, we used a histological grading system to evaluate the adhesions by adding quantity points (with 0 indicating no apparent adhesions; 1, several scattered filaments; 2, a number of filaments; and 3, countless filaments) and quality points (with 0 indicating no apparent adhesions; 1, regular, elongated, fine filamentous adhesions; 2, irregular, mixed, shortened, filamentous adhesions; 3, dense, not filamentous adhesions), as previously reported^24,25.

Mechanical Evaluation

To evaluate peritendinous adhesions and tendon repair, the work of flexion and maximal tensile strength, respectively, were measured with use of a universal testing machine (CR-500-DX-LII; Sun Scientific, Tokyo, Japan). The work of flexion represents the work necessary to overcome the resistant forces from within the tendon sheath against the flexion motion of the digit. One, three, and six weeks after surgery, the rabbit fourth toes (n = 10 per group) were harvested, with the flexor tendon and sheath intact. The proximal end of the flexor digitorum profundus tendon was attached to the crosshead nonslip clamp of the universal testing machine (bending test mode), and the actuator pulled the tendon at 20 mm/min until 120° flexion was achieved. The force and excursion of the clamp were directly measured (see Appendix), and the work of flexion was calculated by integration of the area under the curve^26,27. To measure the maximum tensile strength, the sutured rat Achilles tendon (at three weeks after surgery) (n = 6 per group) and the rabbit flexor digitorum profundus tendon of the second toe (at one, three, or six weeks after surgery) (n = 7 per group) were harvested, and the proximal and distal ends of the tendon were fixed with nonslip clamps attached to the universal testing machine (tensile test mode). The tendon was pulled uniaxially at 600 mm/min until terminal rupture occurred (see Appendix), and the maximum tensile strength was recorded as the maximum tension force^26,28.

Cell Culture in Double Chambers

To learn the mechanism underlying the anti-adhesion effect of MPC hydrogel, we evaluated the effects of MPC polymer on cell migration and viability with use of mouse fibroblastic NIH3T3 cells (RIKEN Cell Bank, Tsukuba, Japan) cultured in Dulbecco's modified Eagle medium (D-MEM; Wako Pure Chemical Industries, Osaka, Japan) containing 2% or 10% fetal bovine serum (FBS) in a double chamber dish divided by a porous membrane (Transwell culture insert; Corning, Corning, New York). The cells were inoculated at a density of 5.0 × 10⁵/well in the upper chamber containing 2% FBS medium with and without the MPC polymer coating (depth, 2.9 mm) at the bottom. After twenty-four hours of culture, cell migration was determined by the number of cells that moved to the lower chamber containing 10% FBS medium because of the difference in serum concentration²⁹. The lower surface of the division membrane was stained with Giemsa (Sigma, St. Louis, Missouri)³⁰. Cell viability or MPC biocompatibility was evaluated by means of MTT assay with use of a cell counting kit (Cell Counting Kit-8; Dojindo Laboratories, Kumamoto, Japan) on NIH3T3 cells that were seeded at a density of 5.0 × 10⁵ cells/well in the upper chamber (containing 10% FBS medium) in the absence and presence of the MPC polymer coating in the lower chamber (containing the same concentration of FBS)²⁹.

Statistical Analysis

The number and histological grade of fibrous adhesions were evaluated with use of the Mann-Whitney U test. The work of flexion, maximum tensile strength, cell number in the cell migration assay, and absorbance in the cell viability assay were evaluated with the Welch t test. The level of significance was set at p < 0.05.

Source of Funding

This study was supported by a Health and Welfare Research Grant for Translational Research (H19-006) from the Japanese Ministry of Health, Labor, and Welfare. The sponsor had no role in study design, data collection, data analysis, data interpretation, or writing of the manuscript.

Results

Effects of a Local Application of MPC Hydrogel Formed from 2.5% or 5.0% PMBV in the Rat Achilles Tendon Model

Our preparatory in vitro and in vivo analyses demonstrated that the concentration of PMBV that formed the optimum MPC hydrogel for clinical use was 2.5% or 5.0% (see Appendix). Although there were severe peritendinous adhesions that prevented the passage of a spatula under the sutured Achilles tendon in the control group after three weeks, a spatula could pass under the tendon in the MPC hydrogel groups (Fig. 1, A). The passage was qualitatively easier in the 5.0% PMBV hydrogel group than in the 2.5% PMBV group. Peritendinous adhesions, as determined by the fibrous adhesion number, were more than 60% reduced by the 5.0% PMBV hydrogel (p = 0.031) but were not significantly affected by the 2.5% PMBV hydrogel (p = 0.349) (Fig. 1, B, upper graph). In contrast, tendon healing, as determined on the basis of the maximum tensile strength as measured with a rheometer, was comparable in the three groups (Fig. 1, B, lower graph). Hence, we decided to use 5.0% PMBV for the hydrogel formation for the rabbit model.

Fig. 1

Photographs and bar graphs illustrating the effect of a local application of the MPC hydrogel (50 µL), formed from a mixture of PMBV (2.5% or 5.0%) and 2.5% PVA, on peritendinous adhesions and tendon healing in the rat Achilles tendon model. A: Photographs showing the passage of a spatula under the sutured tendon three weeks after the local application of distilled water (control) or the MPC hydrogel. Scale bars = 1 mm. B: Bar graphs showing the fibrous adhesion number and maximum tensile strength, representing peritendinous adhesions and tendon healing, respectively, three weeks after the local application of distilled water (control) or the MPC hydrogels. Data are expressed as the mean (bars) and the standard error (error bars) for six tendons per group. *p < 0.05 vs. control.

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Effects of a Local Application of MPC Hydrogel Containing 5.0% PMBV in the Rabbit Flexor Digitorum Profundus Tendon Model

Three weeks after surgery, there were severe peritendinous adhesions that prevented the passage of a vessel loop under the sutured site in the control group whereas few or no peritendinous adhesions were observed in the MPC hydrogel group, so that a vessel loop could pass under the tendon even after six weeks (Fig. 2, A). Histological analyses of the interfaces between tendon and subcutaneous tissue (Fig. 2, B, upper three panels) and between tendon and bone (Fig. 2, B, lower three panels) showed that peritendinous adhesion tissues appeared at one week and the fibrous tissue increased thereafter in both interfaces of the control group. In the MPC group, the formed MPC hydrogel remained at both interfaces at three weeks and disappeared at six weeks. Neither inflammatory reaction nor peritendinous adhesion tissue formation was observed around the MPC hydrogel throughout the observation periods. The histological adhesion grade confirmed that peritendinous adhesions were significantly lower in the MPC group than in the control group at three and six weeks (p = 0.043 and 0.013, respectively) (Fig. 2, C). In the mechanical analyses involving the rheometer, peritendinous adhesions as determined by the work of flexion were 27% decreased by the MPC hydrogel at three weeks (p = 0.046) (Fig. 2, D, upper graph). The maximum tensile strength representing the tendon healing was not impaired but instead was increased by 55% in the MPC hydrogel group at six weeks (p = 0.048) (Fig. 2, D, lower graph).

Fig. 2

Photographs, photomicrographs, and bar graphs illustrating the effect of local application of MPC hydrogel (50 µL), formed from a mixture of 5.0% PMBV and 2.5% PVA, on peritendinous adhesions and tendon healing in the rabbit flexor digitorum profundus tendon model. A: Photographs showing the passage of a vessel loop under the sutured tendons at one, three, and six weeks after the local application of distilled water (control) or the MPC hydrogel. Scale bars = 1 mm. B: Photomicrographs of the interfaces between tendon (T) and subcutaneous tissue (SC) (upper three panels) and between tendon (T) and bone (B) (lower three panels) at one, three, and six weeks (hematoxylin and eosin). Peritendinous adhesion tissue (A), MPC hydrogel (M), and the interface without peritendinous adhesions (arrowheads) are also indicated in the photomicrographs. Scale bars = 50 µm. C: Bar graph showing histological adhesion grade (determined as quantity points plus quality points, with a possible grade of 0 to 6) of the sutured tendons at one, three, and six weeks. Data are expressed as the mean (bars) and the standard error (error bars) for five tendons per group. *p < 0.05 vs. control. D: Bar graphs illustrating the mechanical properties that were analyzed, specifically, the work of flexion for the evaluation of peritendinous adhesions (upper graph) and the maximum tensile strength for the tendon healing (lower graph) at one, three, and six weeks. Data are expressed as the mean (bars) and the standard error (error bars) for seven to ten tendons per group. *p < 0.05 vs. control.

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Mechanism Underlying the Anti-Adhesion Effect of MPC Hydrogel Using Cell Cultures

The cell migration as determined by the number of cells that moved from the upper chamber to the lower chamber because of the difference in the serum concentration was decreased to 1/10 by the MPC hydrogel (5.0% PMBV and 2.5% PVA) that covered the bottom of the upper chamber (p = 0.015) (Fig. 3, A). In contrast, the cell viability as determined by MTT assay in the upper chamber was not affected by the MPC hydrogel that covered the bottom of the lower chamber containing the same serum concentration (Fig. 3, B). These results indicate that the inhibition of cell migration was not due to cytotoxicity of the MPC hydrogel but probably was due to the microstructure, which physically blocked passage of the cells.

Fig. 3

Assays for cell migration and viability were performed with use of fibroblastic NIH3T3 cells cultured in a double chamber dish divided by a porous membrane. A, Top: Cell migration was determined by the number of cells that moved to the lower chamber because of the difference in serum (FBS) concentration. Middle: Giemsa staining of the lower surface of the division membrane. Scale bars = 100 µm. Bottom: Bar graph illustrating the cell number in the lower chamber. Data are expressed as the mean (bars) and the standard error (error bars) for three wells per group. *p < 0.05 vs. control. B, Top: Cell viability in the upper chamber with and without the MPC hydrogel coating in the lower chamber. Middle: Histological appearance of the cells on the upper surface of the division membrane. Scale bars = 100 µm. Bottom: Bar graph showing the viability of the cells in the upper chamber as determined by the absorbance with use of MTT assay. Data are expressed as the mean (bars) and the standard error (error bars) for three wells per group. There was no significant difference between the two groups.

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Discussion

In the present two animal models, the MPC hydrogel efficiently reduced peritendinous adhesions without impairing healing of the sutured tendon (Figs. 1 and 2). Compared with conventional anti-adhesion agents, the MPC hydrogel has several advantages for clinical use. First, the hydrogel is formed in situ immediately after a local injection and mixture of two aqueous solutions, PMBV and PVA, for ease of use in the clinical setting. The degradation rate of the formed hydrogel was controllable by the PMBV concentration, and the optimum concentration of PMBV for the tendon healing was determined to be 5.0% with use of in vitro and in vivo assay systems. The MPC hydrogel formed from 5.0% PMBV was shown to remain for three weeks (Fig. 2, B), which covers the critical phases of tendon healing^2-4.

A more important mechanism underlying the anti-adhesion effect is the honeycomb microstructure with nanometer-scaled pores (400 to 800 nm in diameter) of the MPC hydrogel; these are assumed to block the passage of extrinsic fibroblastic cells (>8 to 10 µm in diameter) that form peritendinous adhesions but to allow the passage of cytokines and growth factors for tendon healing^18,31,32. This may explain the results of the cell culture, which showed that the MPC hydrogel physically prevented cell migration without affecting cell viability (Fig. 3). The maximum tensile strength within the MPC hydrogel group in the rabbit flexor digitorum profundus tendon model was not impaired but instead was unexpectedly increased at six weeks (Fig. 2, D, lower graph), perhaps because of the continuous passage of cytokines and growth factors without being trapped by adhesions around the tendon repair site. Repetitive micromotions of the tendon may occur even during cast immobilization and may gradually increase the tensile strength at the repair site. In the MPC hydrogel group, less adhesion at the suture site may have resulted in more appropriate loading and better recovery.

In addition to its role as a physical barrier, the strongest and most characteristic advantage of the MPC hydrogel is its excellent biocompatibility (indicated by the absence of foreign-body reactions) as the side chain of this polymer is composed of phosphorylcholine mimicking the neutral phospholipids of biomembranes¹¹. Many synthetic materials for adhesion resistance have failed because they stimulated inflammatory responses or allowed ingrowth of adhesions around the materials^20,33-37. However, the bioinert MPC hydrogel should be able to overcome this problem in clinical settings and the MPC polymer has already been clinically used on the surface of other medical devices to suppress biological reactions^11-17.

Considering the urgent need for successful healing of severed tendons with smooth digital motion, this nanotechnology possibly would improve the quality of care of patients with tendon injury, especially in the hand at the zone-II area of the digital flexor tendon. However, because many drugs, materials, and biomaterials that have been proved to be effective in experimental studies have not entered clinical practice^{20,25,27,33-35,37-40}, we should note that it remains unknown whether the improvements associated with the MPC hydrogel are clinically relevant. The use of rodents may not be directly translatable to human clinical medicine as the physical and anatomical features of rodent tendons do not match the human anatomy⁴¹. The results of the present study need to be confirmed in other models that are more similar to humans, such as dogs, chickens, and nonhuman primates, before considering that this compound has anything more than potential at this point.

In summary, the MPC hydrogel reduced peritendinous adhesions without impairing tendon healing in two animal models. This effect may be due to its excellent biocompatibility and the formation of a microstructure that prevents the passage of cells. MPC hydrogel seems to be a promising material for the reduction of peritendinous adhesions after tendon repair in clinical settings.

Appendix

Figures and a table showing the method of mechanical evaluation, in vitro and in vivo analyses to determine the concentration of PMBV that forms the optimum MPC hydrogel, and the maximum tensile strengths of intact rat Achilles tendon and rabbit flexor digitorum profundus tendon are available with the electronic version of this article on our web site at jbjs.org (go to the article citation and click on "Supporting Data").

Acknowledgements

Note: The authors thank Akio Terashima, Toshimitsu Hori, Takashi Maeda, Yuji Ogata, Katsuhiko Ase, and Reiko Yamaguchi for their excellent technical assistance.

References

Gelberman RH; Manske PR; Akeson WH; Woo SL; Lundborg G; Amiel D. Flexor tendon repair. J Orthop Res. 1986;4:119-28.[PubMed][CrossRef]

Beredjiklian PK. Biologic aspects of flexor tendon laceration and repair. J Bone Joint Surg Am. 2003;85:539-50.[PubMed]

Ingraham JM; Hauck RM; Ehrlich HP. Is the tendon embryogenesis process resurrected during tendon healing?Plast Reconstr Surg. 2003;112:844-54.[PubMed][CrossRef]

Sharma P; Maffulli N. Tendon injury and tendinopathy: healing and repair. J Bone Joint Surg Am. 2005;87:187-202.[PubMed][CrossRef]

Lister G. Pitfalls and complications of flexor tendon surgery. Hand Clin. 1985;1:133-46.[PubMed]

Taras JS; Gray RM; Culp RW. Complications of flexor tendon injuries. Hand Clin. 1994;10:93-109.[PubMed]

Ishihara K; Aragaki R; Ueda T; Watenabe A; Nakabayashi N. Reduced thrombogenicity of polymers having phospholipid polar groups. J Biomed Mater Res. 1990;24:1069-77.[PubMed][CrossRef]

Ishihara K; Ziats NP; Tierney BP; Nakabayashi N; Anderson JM. Protein adsorption from human plasma is reduced on phospholipid polymers. J Biomed Mater Res. 1991;25:1397-407.[PubMed][CrossRef]

Ishihara K; Oshida H; Endo Y; Ueda T; Watanabe A; Nakabayashi N. Hemocompatibility of human whole blood on polymers with a phospholipid polar group and its mechanism. J Biomed Mater Res. 1992;26:1543-52.[PubMed][CrossRef]

Ishihara K; Nomura H; Mihara T; Kurita K; Iwasaki Y; Nakabayashi N. Why do phospholipid polymers reduce protein adsorption?J Biomed Mater Res. 1998;39:323-30.[PubMed][CrossRef]

Ishihara K; Shinozuka T; Hanazaki Y; Iwasaki Y; Nakabayashi N. Improvement of blood compatibility on cellulose hemodialysis membrane: IV. Phospholipid polymer bonded to the membrane surface. J Biomater Sci Polym Ed. 1999;10:271-82.[PubMed][CrossRef]

Lewis AL; Tolhurst LA; Stratford PW. Analysis of a phosphorylcholine-based polymer coating on a coronary stent pre- and post-implantation. Biomaterials. 2002;23:1697-706.[PubMed][CrossRef]

Myers GJ; Johnstone DR; Swyer WJ; McTeer S; Maxwell SL; Squires C; Ditmore SN; Power CV; Mitchell LB; Ditmore JE; Aniuk LD; Hirsch GM; Buth KJ. Evaluation of Mimesys phosphorylcholine (PC)-coated oxygenators during cardiopulmonary bypass in adults. J Extra Corpor Technol. 2003;35:6-12.[PubMed]

Goda T; Ishihara K. Soft contact lens biomaterials from bioinspired phospholipid polymers. Expert Rev Med Devices. 2006;3:167-74.[PubMed][CrossRef]

Moro T; Takatori Y; Ishihara K; Konno T; Takigawa Y; Matsushita T; Chung UI; Nakamura K; Kawaguchi H. Surface grafting of artificial joints with a biocompatible polymer for preventing periprosthetic osteolysis. Nat Mater. 2004;3:829-36.[PubMed][CrossRef]

Moro T; Takatori Y; Ishihara K; Nakamura K; Kawaguchi H. 2006 Frank Stinchfield Award: grafting of biocompatible polymer for longevity of artificial hip joints. Clin Orthop Relat Res. 2006;453:58-63.[PubMed][CrossRef]

Moro T; Kawaguchi H; Ishihara K; Kyomoto M; Karita T; Ito H; Nakamura K; Takatori Y. Wear resistance of artificial hip joints with poly(2-methacryloyloxyethyl phosphorylcholine) grafted polyethylene: comparisons with the effect of polyethylene cross-linking and ceramic femoral heads. Biomaterials. 2009;30:2995-3001.[PubMed][CrossRef]

Konno T; Ishihara K. Temporal and spatially controllable cell encapsulation using a water-soluble phospholipid polymer with phenylboronic acid moiety. Biomaterials. 2007;28:1770-7.[PubMed][CrossRef]

Aspenberg P; Virchenko O. Platelet concentrate injection improves Achilles tendon repair in rats. Acta Orthop Scand. 2004;75:93-9.[PubMed][CrossRef]

Potenza AD. Critical evaluation of flexor-tendon healing and adhesion formation within artificial digital sheaths. J Bone Joint Surg Am. 1963;45:1217-33.[PubMed]

Strick MJ; Filan SL; Hile M; McKenzie C; Walsh WR; Tonkin MA. Adhesion formation after flexor tendon repair: a histologic and biomechanical comparison of 2- and 4-strand repairs in a chicken model. J Hand Surg Am. 2004;29:15-21.[PubMed][CrossRef]

Burns JW; Skinner K; Colt J; Sheidlin A; Bronson R; Yaacobi Y; Goldberg EP. Prevention of tissue injury and postsurgical adhesions by precoating tissues with hyaluronic acid solutions. J Surg Res. 1995;59:644-52.[PubMed][CrossRef]

Yeo Y; Highley CB; Bellas E; Ito T; Marini R; Langer R; Kohane DS. In situ cross-linkable hyaluronic acid hydrogels prevent post-operative abdominal adhesions in a rabbit model. Biomaterials. 2006;27:4698-705.[PubMed][CrossRef]

Tang JB; Shi D; Zhang QG. Biomechanical and histologic evaluation of tendon sheath management. J Hand Surg Am. 1996;21:900-8.[PubMed][CrossRef]

Moran SL; Ryan CK; Orlando GS; Pratt CE; Michalko KB. Effects of 5-fluorouracil on flexor tendon repair. J Hand Surg Am. 2000;25:242-51.[PubMed][CrossRef]

Ferguson RE; Rinker B. The use of a hydrogel sealant on flexor tendon repairs to prevent adhesion formation. Ann Plast Surg. 2006;56:54-8.[PubMed][CrossRef]

McCombe D; Kubicki M; Witschi C; Williams J; Thompson EW. A collagen prolyl 4-hydroxylase inhibitor reduces adhesions after tendon injury. Clin Orthop Relat Res. 2006;451:251-6.[PubMed][CrossRef]

Alavanja G; Dailey E; Mass DP. Repair of zone II flexor digitorum profundus lacerations using varying suture sizes: a comparative biomechanical study. J Hand Surg Am. 2005;30:448-54.[PubMed][CrossRef]

Morioka K; Tanikawa C; Ochi K; Daigo Y; Katagiri T; Kawano H; Kawaguchi H; Myoui A; Yoshikawa H; Naka N; Araki N; Kudawara I; Ieguchi M; Nakamura K; Nakamura Y; Matsuda K. Orphan receptor tyrosine kinase ROR2 as a potential therapeutic target for osteosarcoma. Cancer Sci. 2009;100:1227-33.[PubMed][CrossRef]

Tsai WC; Tang FT; Wong MK; Pang JH. Inhibition of tendon cell migration by dexamethasone is correlated with reduced alpha-smooth muscle actin gene expression: a potential mechanism of delayed tendon healing. J Orthop Res. 2003;21:265-71.[PubMed][CrossRef]

Reed C; Fu ZQ; Wu J; Xue YN; Harrison RW; Chen MJ; Weber IT. Crystal structure of TNF-alpha mutant R31D with greater affinity for receptor R1 compared with R2. Protein Eng. 1997;10:1101-7.[PubMed][CrossRef]

Uhal BD; Ramos C; Joshi I; Bifero A; Pardo A; Selman M. Cell size, cell cycle, and alpha-smooth muscle actin expression by primary human lung fibroblasts. Am J Physiol. 1998;275:998-1005.

Wheeldon T. The use of cellophane as a permanent tendon sheath. J Bone Joint Surg Am. 1939;21:393-6.

Hunter JM; Salisbury RE. Flexor-tendon reconstruction in severely damaged hands. A two-stage procedure using a silicone-Dacron reinforced gliding prosthesis prior to tendon grafting. J Bone Joint Surg Am. 1971;53:829-58.[PubMed]

Stark HH; Boyes JH; Johnson L; Ashworth CR. The use of paratenon, polyethylene film, or Silastic sheeting to prevent restricting adhesions to tendons in the hand. J Bone Joint Surg Am. 1977;59:908-13.[PubMed]

Peterson WW; Manske PR; Dunlap J; Horwitz DS; Kahn B. Effect of various methods of restoring flexor sheath integrity on the formation of adhesions after tendon injury. J Hand Surg Am. 1990;15:48-56.[PubMed][CrossRef]

Hanff G; Hagberg L. Prevention of restrictive adhesions with expanded polytetrafluoroethylene diffusible membrane following flexor tendon repair: an experimental study in rabbits. J Hand Surg Am. 1998;23:658-64.[PubMed][CrossRef]

Isik S; Oztürk S; Gürses S; Yetmez M; Güler MM; Selmanpakoglu N; Günhan O. Prevention of restrictive adhesions in primary tendon repair by HA-membrane: experimental research in chickens. Br J Plast Surg. 1999;52:373-9.[PubMed][CrossRef]

Kobayashi M; Toguchida J; Oka M. Development of polyvinyl alcohol-hydrogel (PVA-H) shields with a high water content for tendon injury repair. J Hand Surg Br. 2001;26:436-40.[PubMed][CrossRef]

Güdemez E; Eksioglu F; Korkusuz P; Asan E; Gürsel I; Hasirci V. Chondroitin sulfate-coated polyhydroxyethyl methacrylate membrane prevents adhesion in full-thickness tendon tears of rabbits. J Hand Surg Am. 2002;27:293-306.[PubMed][CrossRef]

Carpenter JE; Hankenson KD. Animal models of tendon and ligament injuries for tissue engineering applications. Biomaterials. 2004;25:1715-22.[PubMed] [CrossRef]

Topics

percutaneous balloon mitral valvuloplasty ; cell culture techniques ; achilles tendon ; adhesions ; hydrogel ; phospholipids ; polymers ; oryctolagus cuniculus ; tendon ; tendon repair

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Noriyuki Ishiyama, Toru Moro, Takashi Ohe, Toshiki Miura, Kazuhiko Ishihara, Tomohiro Konno, Tadashi Ohyama, Mizuna Kimura, Masayuki Kyomoto, Taku Saito, Kozo Nakamura, Hiroshi Kawaguchi; Reduction of Peritendinous Adhesions by Hydrogel Containing Biocompatible Phospholipid Polymer MPC for Tendon Repair. The Journal of Bone & Joint Surgery. 2011 Jan;93(2):142-149.

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