CA2215200C

CA2215200C - Biodegradable device

Info

Publication number: CA2215200C
Application number: CA002215200A
Authority: CA
Inventors: Thomas Gilchrist; David Michael Healy
Original assignee: Tyco Healthcare Group LP
Current assignee: Covidien LP
Priority date: 1995-04-01
Filing date: 1996-04-01
Publication date: 2007-06-19
Anticipated expiration: 2016-04-01
Also published as: CA2215200A1

Abstract

There is provided a device (1) to promote healing of cut tissue members, suc h as nerves, tendon or muscles, within a body. The device (1) is of hollow construction and comprises apertures (2, 3) into whi ch the cut ends of the tissue members are placed and fixed, usually by a fibrin-based tissue glue. Located between the apertures (2, 3) is a substance to promote healing of the tissue member such as, for example, nerve growth factor. Optionally the device (1) may be used in conjunction with the external reservoir of the substance and/or with a time-operated pump to deliver the substance to the device (1). The device (1) is biodegradable and is preferably composed of watersoluble glass.

Description

1 "BIODEGRADABLE DEVICE"

2

3 The present invention relates to a biodegradable device

4 to aid healing.
6 Advances in surgical techniques, particularly micro-7 surgical techniques, have enabled operations for re-8 joining or aligning severed nerves and blood vessels to 9 be undertaken. However, to be successful such operations still rely upon the natural healing and 11 regeneration processes of the body. Thus, even where 12 the surgeon has exerted considerable skill in aligning 13 nerve ends, there will be cases where the parts of 14 nerves fail to re-join, or where the healing process is so slow that the effector muscle has atrophied by the 16 time that the motor nerve connection becomes effective.

18 Healing, for example nerve regeneration, remains an 19 essentially biological process. Even the most advanced micro-surgical techniques for repairing damaged tissue 21 members merely optimise the environment for the natural 22 process. It is now believed that micro-surgery has 23 maximised the mechanical processes for body repair, but 24 a need still exists for enhancing the healing process still further.

Tubes have been used to repair severed nerves, but have enjoyed little success because the non-biodegradable tubes remained after the regenerating nerve had been established and impeded subsequent maturation of the nerve.
GB-A-2,099,702 describes a structural support member for skeletal and tissue members comprised of a biodegradable glass. However, for the healing process to be successful it is essential that the correct chemical environment is created to optimise the regeneration of the damaged body part, whilst protecting that part from the body's own defence system which can be activated against implanted foreign bodies.

SUMMARY OF THE INVENTION

In one aspect, there is provided a biodegradable device being of hollow construction having first and second apertures, each aperture being adapted to receive a cut end of a tissue member, said device having fixant means adapted to secure the cut ends of the tissue member and a free space between the apertures, said free space containing a substance to facilitate healing of said tissue member, said device formed at least in part from biodegradable glass which biodegrades over a pre-selected period, and said device comprising an injection port enabling access to the interior volume of the device.
In another aspect, there is provided use of a device as defined herein for treating a cut tissue member of a human or non-human animal body.

- 2a -DETAILED DESCRIPTION
Generally the device will be tubular. For example the device may be an open-ended tube, the two open ends forming the apertures for receiving the ends of the cut tissue member.

For convenience of manufacture the device may be essentially an open-ended cylinder of uniform internal cross-section. Alternatively, the device may incorporate a reservoir portion, in which reserves of the substance are located. In this embodiment the device may be tubular, but have an internal cross-1 section of varying diameter, for example of increased 2 diameter in the portion between said apertures. To 3 optimise the healing together of the two cut ends 4 secured in the device, the apertures may be arranged to face each other. However, in certain instances this 6 arrangement may not be essential, and the aperatures 7 need not be aligned.

9 The device of the present invention may be formed from a biodegradable glass. Such glasses are known to those 11 skilled in the art and the composition of the glass may 12 be adjusted to produce a glass composition that 13 biodegrades over the period required, for example 1 to 14 6 months, or 1 to 3 months. Desirably the products resulting from degradation of the glass are 16 physiologically compatible.

18 Additionally, the glass composition may itself be used 19 as a vehicle to deliver biologically active agents in a controlled release manner over the period during which 21 healing occurs. Controlled Release Glasses (CRG) are 22 inorganic polymers, normally based on phosphates of 23 sodium and calcium, which have been converted into a 24 glassy form by melting the constituents at about 1000 C. CRGs dissolve in water completely leaving no 26 solid residue.

28 The rate of dissolution can be selected by adjustment 29 of the composition and physical form of the CRG and is constant for as long as any of the material remains.
31 The product can be produced in many physical forms; as 32 a powder or granules, fibre or cloth, tubes, or as cast 33 blocks of various shapes.

As stated above, suitable biodegradable glasses are 36 known in the art, but particular mention may be made of 1 the glasses disclosed in WO-A-90/08470 of Giltech 2 Limited. Typically, the glass compositions may 3 comprise:

Na20 7-33 mole%
6 K20 0-22 mole%
7 CaO 0-21 mole%
8 MgO 0-22 mole%
9 P205 46-49 mole%
11 Such glass compositions may achieve solution rates of 12 from 0.03 to 3.0 mgcm'2hr-t in de-ionised water at 37 C.

14 Elements other than sodium and calcium, including most metals as their oxides and a limited number of 16 inorganic anions, can be included in the composition of 17 the glass. These elements, which may be biologically 18 active, can then be delivered at a constant rate into 19 an ambient aqueous medium (for example a physiological fluid) as the CRG dissolves. This has found 21 application in veterinary medicine as a means of 22 delivering such diverse substances as trace elements, 23 anthelmintics and vaccines. Incorporation of a silver 24 source (for example silver orthophosphate) into the Na20-CaO-P2O5 systems offers the possibility of producing 26 a CRG capable of releasing silver ions over a highly 27 defined time, into biological systems with safety.

29 In the course of developments of this type the biocompatibility and absence of toxicity of CRG based 31 on Na20-(Ca,Mg)O-PZ05 with and without other constituents 32 have been investigated. In applications differing as 33 widely as use in orthodontics devices [see Savage, 34 Brit. J. of Orthodontics 9: 190-193 (1982)], and in controlled supply of Cu, Co and Zn in cattle [see Drake 36 et al, Biochem. Soc. Trans. 13 : 516-520 (1985)], no 1 ill effects were observed.' When CRG pellets were 2 implanted subcutaneously, intramuscularly and 3 intraperitoneally in rats, sheep and cattle, reaction 4 at the implant site was limited to a sterile fibrous

5 encapsulation less well developed than that expected

6 from biocompatible surgical materials [see Allen et al,

7 Vet. Soc. Commun 2 : 78-75 (1978)]. Other application

8 of CRG in the Na2O-CaO-PzO5 system have been found as

9 potential bone graft adjuncts/substitutes. No sign of cytotoxicity was observed after soft tissue 11 implantation in sheep [see Burnie et al, Biomaterials 2 12 : 244-246 (1981)]. In further experiments with bone no 13 ill effects nor bioincompatibility could be detected 14 [see Burnie et al, "Ceramics in Surgery" Ed Vincenzini, Elseveier Scientific, 1983, pages 169-176; Burnie et 16 al, J. Bone & Joint Surgery 65B 3: 364-365 (1983);
17 Duff et al, Strathclyde Bioengineering Seminars, 18 Biomaterials in Artificial Organs, and Paul et ai, 19 Macmillan Press, 1984, pages 312-317].
21 The glass composition may include one or more metal 22 ions which are slowly released from the composition to 23 facilitate healing. Mention may be made of K, Mg, Zn, 24 Al, Se, Si, Fe, Ag, Cu, Mn, Ce and/or Au.
26 In particular the glass composition may be manufactured 27 to provide a potassium-rich environment, which may be 28 useful in aiding healing of the tissue member, 29 especially nerves.
31 The substance located in the device will be selected to 32 facilitate healing of the cut tissue member. The 33 viscosity, osmolality and pH of the substance should 34 therefore be chosen to be physiologically compatible with the type of tissue to be healed. The substance 36 may optionally contain one or more physiologically 1 active agents and mention may be made of growth factors 2 (especially growth factors specific for the type of 3 tissue concerned, such as nerve growths factors for 4 nerve re-generation), anti-coagulants, agents to combat infections (for example antibiotics, silver ions etc) 6 and the like. Mention may be made of platelet 7 released and PDGF, Nerve growth factor, Keratinocyte 8 stimulation factors, Insulin-like growth factor, 9 Interleukins, peptides, enzymes and other topical agents, oxygenators and free radical scavengers, 11 enzymes and nutritional agents such as proteins and 12 vitamins. Optionally the surfaces of the glass device 13 may be coated with silicone to reduce thrombogenesis.

Over a number of years a great deal of evidence has 16 emerged from in vitro experiments to suggest that the 17 group of substance known as 'nerve growth factors' or 18 'nerve cell rescue factors' may enhance the 19 regeneration process which takes place after a nerve is injured and repaired. There are now many such 21 substances awaiting evaluation. Some are thought to 22 act preferentially on either motor or sensory nerves 23 and the potential for their use in chemically 24 manipulating and improving the results of surgical nerve repair is enormous. Despite at least 20 years of 26 study in the laboratory little or no success has been 27 achieved in the method of delivery to this site of 28 injury and also because the tests which are used to 29 quantify nerve repair are insufficiently sensitive to resolve the small (but most useful) benefits which 31 growth factors may bring. For a substance to have 32 maximal effect is must be delivered at the site of 33 regeneration, at an appropriate and maintained 34 concentration and at the time at which its effect on the growing nerve axons will be most effective. To 36 achieve this, delivery must be constant at the site of 1 injury over the growing period and diffusion away from 2 this site must be insufficient for the local 3 concentration to fall below effective values. Lundborg 4 [see G. Lundborg, Nerve Injury and Repair, 1988, Edinburgh Churchill-Livingston] has to a small extent 6 achieved this by wrapping the site in silicon tubes 7 containing growth factors. However there is still an 8 inadequate concentration over time and the permanent 9 tube constricts the growing nerve in its maturation phase. The end result is worse rather than better and 11 no surgeon in human practice would contemplate a second 12 operation to remove a silicon tube.

14 The biodegradable device of the present invention offers two features which address these issues. First 16 the device can be made to dissolve over a timecourse 17 which would include the period of growth in length when 18 growth factors could be delivered to an isolated 19 environment but dissolution would occur before the non-growth-factor-dependant phase of maturation (growth in 21 diameter). Secondly, growth factors could be delivered 22 into the device through a side hole by means of an 23 osmotic pump. If the outlet silicon rubber tube is 24 glued into the device a watertight system is effected.
Using proprietary osmotic pumps, growth factors can be 26 delivered in appropriate constant concentration for 27 four weeks after repair. This encompasses the time for 28 growth factor-dependant regeneration. At the end of 29 this time the device will biodegrade and the pump and its tubing can be removed from its remote subcutaneous 31 site under local anaesthetic in a very small and simple 32 operation. The nerve is thus left unimpeded to mature.

34 The substance may be any means to facilitate healing, including cellular matrices which encourage and 36 mechanically guide regeneration e.g. of nerve or 1 muscle, and/or humeral substances such as chemical 2 growth factors. By increasing the concentration of the 3 supplied substance at the site of injury and 4 regeneration the latter may be enhanced and its specificity improved.

7 The fixant may be any means of securing the cut end of 8 the tissue member into an aperture of the device.
9 Desirably the fixant substantially seals the tissue member end into the aperture. Mention may be made of 11 sutures, clips and other mechanical means, but 12 desirably the fixant should be biodegradable. Thus 13 physiologically compatible "glues" may be preferred.
14 One particular example is a fibrin-based tissue glue.
16 The device itself may comprise means to secure a tissue 17 member end in an aperture of the device. For example, 18 the internal diameter of the device may decrease in the 19 proximity of the aperture. In one preferred embodiment the device includes internal barbs which grip the 21 tissue member once inserted. Desirably however a 22 physiologically acceptable "glue" is used to seal the 23 aperture after insertion of the tissue member. Thus 24 the glue can be used to protect the damaged ends of the tissue member from the body's defence mechanisms.

27 The device of the present invention is particularly 28 useful for enhancing the healing of severed nerves, 29 including individual nerve fibres as well as nerve bundles. The device may also be of utility for aiding 31 the healing of tissue members such as tendons, blood 32 vessels (especially capillary blood vessels), muscle 33 fibres and ducts.

The ends of the tissue member may be inserted into the 36 aperture of the device by any suitable means. For 1 example, the aperture may be large enough for the 2 tissue member end to be simply placed therein; the end 3 then being secured by any suitable means, preferably a 4 4 physiologically acceptable glue. However in certain circumstances it may be desirable for the aperture to 4 6 be of similar internal diameter to the external 7 diameter of the tissue member. In this instance a 8 suture, threaded through the device is drawn through 9 the tissue member end which can then be pulled through the aperture as required.

12 In one embodiment the device has a semi-porous or 13 porous region, preferably located between said 14 aperatures. Prior to implantation the device is exposed to physiologically useful agents which may be 16 taken up into the porous or semi-porous region of the 17 device for release after implantation. The agents may 18 facilitate the healing of the tissue member. Thus, the 19 same device could be used to facilitate healing for different types of tissue members, but will be adapted 21 specifically for each depending on the physiologically 22 useful agents taken up into the porous or semi-porous 23 region. Following implantation, said physiologically 24 useful agent(s) can be injected adjacent to the implant, pass through the porous region and onto the 26 tissue member under repair.

28 In a further embodiment, the device may include an 29 opening to enable introduction of a substance into the device before implantation and/or after implantation.
31 The opening may optionally also be used for exit of the 32 suture pulling the end of the tissue member through the 33 aperature. In one particular embodiment the device of 34 the present invention may be replenished with the substance after implantation. Thus, for example, the 36 device could be connected to a reservoir external to 1 the patient and/or a time-operated pump to 2 automatically replenish the substance in said device.

4 In a further aspect, the present invention provides a 5 method to facilitate healing of a cut tissue member, 6 said method comprising inserting each end of said 7 tissue member into a separate aperture therefor in the 8 device of the present invention and securing the tissue 9 member ends into said apertures by means of a fixant.
11 The technique of inserting the tissue member ends, for 12 example nerve ends, into a tube and securing them there 13 with fibrin-based tissue glue is very simple. This 14 technique dispenses with the need for an operating microscope, expensive microsurgical sutures and 16 instruments and the need for a trained microsurgeon.
17 It may thus have considerable implications for current 18 surgical practice and could further extend the repair 19 of nerves to underdeveloped countries where at present nerve injuries may be untreatable.

22 In a further embodiment the device of the present 23 invention may be used totest theeffect of different 24 factors on tissue healing. For example the device may be considered as a model system in which growth factors 26 may be tested to find out whether and to what extent 27 such factors may be helpful in promoting and directing 28 the natural process of regeneration.

In a yet further embodiment the present invention 31 provides a kit to aid healing of a cut tissue member, 32 said kit comprising a device of hollow construction 33 having two apertures adapted to receive the cut ends of 34 a tissue member; said kit further comprising a physiologically acceptable fixant and a substance to 36 aid healing of said tissue member.

1 The device of the present invention may also be used in 2 vitro to promote growth of a tissue member; the 3 regenerated tissue member may subsequently be used for 4 transplantation, for example to replace a damaged tissue member.

7 In a further aspect, the present invention provides a 8 method of treating a human or non-human animal body 9 having a cut tissue member, said method comprising inserting the cut ends of said tissue member into 11 separate aperatures of the device according to the 12 invention. Optionally the device may be used in 13 conjunction with an external reservoir of the substance 14 and/or with a time operated pump to deliver the substance to the device.

17 Fig. 1 illustrates a biodegradable glass tube suitable 18 for nerve repair.

Fig. 2 illustrates the biodegradable glass tube of Fig.
21 1 having a rubber tubing attached thereto.

23 Fig. 1 shows a biodegradable glass tube 1 suitable for 24 use in the present invention, especially for nerve repair. Tube 1 consists of a hollow, essentially 26 cylindrical, glass body having aperatures 2, 3 at the 27 ends thereof. Two diametrically opposed suture holes 28 4,4' are located in tube 1, close to aperature 2. Two 29 similar diametrically opposed suture holes 5,5' are also located in tube 1, close to aperature 3.
31 Approximately mid-way down the length of tube 1 is an 32 injection port 6, which enables access to the interior 33 volume of tube 1, even when tube 1 is in place within a 34 patient.
36 Fig. 2 illustrates a similar tube 1 to that shown in 1 Fig. 1, having flexible tubing 7 (for example silicone 2 tubing) passed through injection port 6 into the 3 interior volume of tube 1. Tubing 7 may be connected 4 to a pump or reservoir (not shown) containing a {
substance or active agent capable of promoting healing 6 of the body part in question. Once sufficient healing 7 has taken place tubing 7 may be simply removed, without 8 disturbing tube 1.

In use, one of the ends of the damaged body part will 11 be inserted into aperature 2 of tube 1, optionally 12 after trimming the end of the body part. A suture will 13 then be passed through a first suture hole 4, through 14 the end of the body part inserted through aperature 2 and out through suture hole 4'. The ends of the suture 16 will then be securely fastened. Optionally a tissue 17 glue may then be used to seal the body part into the 18 aperature 2 of tube i.

The process described above will then be repeated with 21 the other end of the damaged body part, aperature 3 and 22 suture holes 5,5' of tube 1.

24 Optionally tubing 7 may be passed through injection port 6 into the interior volume of tube 1 and an 26 appropriate substance fed into the free space within 27 tube 1 to provide an environment suitable for healing 28 the body part. The two ends of the body part will 29 gradually grow down the interior of tube 1 and, on meeting will knit together. Alternatively the 31 substance may be simply injected into the free volume 32 within tube 1 by any suitable means (e.g. syringe).

34 For very small body parts (e.g. the sciatic nerve of rats, the common peroneal nerve of rabbits or similarly 36 sized body parts of other animals), the length of the 1 glass tube may be 20-26mm (e.g. 22mm) with an outer 2 diameter of 4-5mm. The tube itself may have a 3 thickness of 1-2mm (e.g. 1.2mm) and the suture holes 4 and injection ports may each typically have a diameter of 0.5-lmm (e.g. 0.7mm).

7 For slightly larger body parts, a larger dimensioned 8 tube will be required, and the dimensions recited above 9 may be adapted as required. For example in sheep, a tube length of 30mm having an outer diameter of 8-9mm 11 and inter diameter of 7mm, with suture hole and port 12 diameter of 1.2-1.3mm may be sufficient.

14 The invention will be further described with reference to the following, non-limiting, examples.

1 Example 1 3 All procedures were performed on rats and under sterile 4 conditions.
6 1. The biceps femoris muscle was retracted. Care was 7 taken not to involve the medial femoral circumflex 8 artery which supplies these muscles.

2. The sciatic nerve was cut about 2cm from the 11 sciatic notch. (Midway down the nerve).

13 3. A biodegradable glass tube (as illustrated in 14 Figure 1) was cut to size enabling 2mm of nerve to extend into the centre of the tube.

17 The glass of the tube was composed as follows:

19 Mole %
Na20 32.0 21 CaO 21.0 22 P205 47.0 24 The glass had a solution rate when annealed of 0.4mgcm'2hr'1 in de-ionised water at 37 C. The tube 26 had a physiological life expectancy of 27 approximately 40-50 days.

29 4. The tube was secured by either suture, clip or glue.

32 5. The animal was kept for over 60 days before 33 undergoing electrophysiological studies and 34 microscopic analysis under anaesthesia.
36 6. EMG was taken to measure conduction velocity. The 1 sciatic nerve was exposed as in step 1 and 2 dissected out 2cm above the graft and 2cm below.
3 EMG was then taken at each point to determine the 4 speed of conduction:

6 (EMG time proximal - EMG time distal) 7. Distance between points 9 The Extensor digitorum longus muscle was chosen

10 for the EMG because the nerve supply is the Deep

11 Peroneal Nerve which is a direct tributary of the

12 Sciatic-Common Peroneal Division.

Results Type of Graft Length (mm) Conduction Healing (if removed) Velocity time (M/s) (days) Tube and Clip 13 4.33 46 Tube and Clip 24 25.26 67 Tube and Clip 25 31.25 114 Tube and Suture 12.5 8.06 47 Tube and Suture 38 19.46 68 Tube and Suture 27 31.76 68 Tube and Suture 15 21.43 90 Tube and Suture 18 21.18 90 Tube and Suture 23 17.04 96 Normal 18 36 -

13 Example 2

14

15 A further study was conducted to establish:

16

17 a) that a biodegradable glass tube (BGT) was

18 compatible with effective nerve repair; and

19 1 b) that the BGT was not toxic to the regenerating 2 nerve or to the surrounding tissue and that the BGT
3 did not provoke a fibrotic tissue reaction or 4 immune response likely to affect nerve regeneration 1 adversely.

3 The experiments were performed in rats. The sciatic 4 nerve was divided and a BGT (as used in Example 1) placed over it. With the BGT pushed to one side the 6 nerve stumps were repaired by epineurial suture. The 7 BGT was then placed at the repair site and fixed in 8 place with epineurial sutures and fibrin glue.
9 Electrophysiological and morphometric assessment was carried out at 100 days. It was found that normal nerve 11 regeneration had taken place and that the BGT had 12 completely dissolved. There was no sign of any adverse 13 reaction.

Example 3 17 This experiment was conducted on New Zealand large white 18 rabbits. In eac+ rabbit the common peroneal nerve was 19 divided and repaired in the upper thigh. The tibial nerve was left intac-_. ?GTs were all as described in 21 Example 1 and all of 1.5cm in length. Each of the 22 methods of repair represented by the contents of the 23 tube are accepted clinical techniques for nerve repair 24 with the exception of the gap which was a control and which would not be expected to be compatible with 26 recovery of nerve function.

28 1) BGT + lcm gap in nerve (control) 29 2) BGT + lcm freeze-thawed muscle autograft (FTMG) 3) BGT + lcm nerve autograft 31 4) BGT + nerve and FTMG short lengths in series to 32 length of lcm 33 5) FTMG without tube (control).

There were 5 rabbits in each group.

1 Each animal was reviewed 6 months after nerve repair.
2 Under anaesthesia the repair site was re-exposed and the 3 nerve was subjected to a number of electrophysiological 4 tests. Some of these tests have become well established as a means of assessing recovery after nerve repair.
6 Others are new tests which are currently being evaluated 7 in an attempt to find tests which will resolve the small 8 but important improvements in nerve regeneration which 9 may be expected where nerve growth factors are used. In all cases the opposite limb was used as a control.

12 After electrophysiological assessment, the segments of 13 repaired and control nerve were excised and processed 14 for microscopic examination. Computerized morphometric assessment was used to measure indices of nerve 16 regeneration such as axon and fibre diameter and G-17 ratio.

19 In group 1 above it was surprising to find that regeneration had taken place albeit to a limited extent.
21 It seems likely that isolating the regenerating nerve 22 within the tube may have improved its chances of 23 crossing the gap. This result speaks well for the fact 24 that the tube does not impede nerve regeneration.
26 In groups 2, 3 and 4 all of the indices of recovery 27 showed comparability with the best results obtained by 28 conventional means. This means that as a supporting 29 medium for either direct repair or repair using short neural and FTMG grafts the BGT system performs as well 31 as anything else currently available.

33 Group 2 demonstrated the best results, with all groups 34 1, 2 and 3 giving successful regeneration of the peripheral nerve. There were no signs of neuroma in any 36 of the groups and the BGT was completely dissolved after 1 the 6 month test period.

Claims

1. A biodegradable device being of hollow construction having first and second apertures, each aperture being adapted to receive a cut end of a tissue member, said device having fixant means adapted to secure the cut ends of the tissue member and a free space between the apertures, said free space containing a substance to facilitate healing of said tissue member, said device formed at least in part from biodegradable glass which biodegrades over a pre-selected period, and said device comprising an injection port enabling access to the interior volume of the device.

2. The device as claimed in claim 1 being an open-ended tube, the two ends of the tube forming the apertures for receiving the ends of the cut tissue member.

3. The device as claimed in either one of claims 1 or 2 having a reservoir portion to hold reserves of said substance.

4. The device as claimed in any one of claims 1 to 3 wherein said glass is a controlled release glass.

5. The device as claimed in claim 4 wherein said glass releases silver ions in a controlled release manner.

6. The device as claimed in any one of claims 1 to 5 wherein said substance is selected from growth factors, anticoagulants, agents to combat infection, platelet releasate, interleukins, peptides, enzymes, nutritional agents, and mixtures thereof.

7. The device as claimed in claim 6 wherein said substance includes nerve growth factor.

8. The device as claimed in any one of claims 1 to 7 wherein the fixant means is adapted to substantially seal the cut end of the tissue member to an aperture of said device.

9. The device as claimed in claim 8 wherein said fixant means is a fibrin-based tissue glue.

10. The device as claimed in any one of claims 1 to 9 having internal barbs to grip the inserted tissue member.

11. The device as claimed in any one of claims 1 to 10 having a semi-porous or porous region located between said apertures.

12. The device as claimed in any one of claims 1 to 11 in combination with an external reservoir of said substance to deliver said substance to said device.

13. The device as claimed in any one of claims 1 to 12 in combination with a time-operated pump to deliver said substance to said device.

14. Use of a device as defined in any one of claims 1 to 11 for treating a cut tissue member of a human or non-human animal body.

15. The use of claim 14 further comprising use of an external reservoir of said substance to deliver said substance to the device.

16. The use of claim 14 further comprising use of a pump to deliver said substance to the device.