Issued May 1975).

1. Introduction

The problem of peripheral nerve regeneration. has been studied intensively by many investigators and has been found to depend on many factors. The most important of these are the patient's age, type of injury, length of tissue, and finally, the technique of nerve repair. A repair is satisfactory when it is executed with as little trauma as possible and when anatomic approximation is achieved. It is difficult to fulfill the requirements without magnification, microsurgical instruments, and the finest of sutures [1, 2]. Despite the advances that have have been made to date, the reestablishment of normal function in the damaged nerve is considered poor [3].

According to Hakstian, "One remaining frontier in which a successful breakthrough has not yet occurred is that of peripheral nerve injury [4]. This is not surprising considering the complex structure of the peripheral nerve over its entire length and the unique manner of healing of this tissue compared to others. Whereas most other tissue, excepting tissue of the central nervous system, survive both distally and proximally of the injury site, nerve tissue (axons) degenerates peripherally [4].

"This research was supported by the National Science Foundation under Grant CH-33873.

Figures in brackets indicate the literature references at the end of this paper.

If results are to improve, in addition to gaining greater understanding of the physiology and the pathology of neural tissue and processes of nerve regeneration, it will be necessary to attain greater sophistication in the surgical manipulation of nerve tissue. It is the latter goal that the present research is concerned with. More specifically, it is concerned with the repair of small nerves, that is, nerves 2 mm in diameter and less such as cranial, digital and facial nerves. Digital nerves are the most frequently severed peripheral nerves, and though. small in size are of critical importance because of their properties of discriminatory touch [5]. Injury to facial nerves, though less common, is of tragic consequence because of loss of communication. through expression, interference with speech and daily activities as eating, drinking, washing and shaving, and the impairment to social and economic welfare produced by psychological effects [6, 7, 8].

Of particular interest to us in the current study has been the use of other tissues or materials to form a channel through which the nerve fibers may grow and bridge the gap between the cut ends. Severed nerves have been drawn through blood vessels [9] or through decalcified bone tubes. Nerve fibers have also been wrapped in sheets of rubber, cargyl membrane, fascia lata or various other materials in an effort to reduce the ingrowth of scar tissue between the ends of the severed fibers. The methods employing organic materials

have been relatively unsuccessful, largely because phagocytes have removed the nerve covering prematurely. A tubulation method has found some success in neurorrhaphy, whereby sheets of Silastic are wrapped about the anastomosis [10, 11, 12, 13, 14.]. The success of this method for facilitating regeneration of nerves is questionable; further it suffers from the drawback of requiring the use of sutures. Methods employing adhesives, especially the cyanoacrylates, as a sutureless technique to anastomose severed nerves, though highly attractive, has so far been ineffective [15, 16].

is essential for successful epineural nerve repairs. If the repair is too loose, a gap results, which will be filled with scar tissue. If the repair is too tight, buckling of the fascicles occurs. According to Bora. even if tension is exactly right, the chances of correct orientation of a fascicular level is only one in four [20]. To overcome the problems of epineural repair, such as gap, overriding, buckling and straddling of fascicles, the fascicular suture technique has been devised [4], whereby two sutures are placed in the perineurium on opposite sides of each fascicle and the severed ends approximated.

The use of sutures is minimized by techniques developed by Millessi, which depends on the use of grafts to eliminate tension [18, 19].

Nerve injuries are commonly repaired by approximating the severed nerve stumps with sutures through the epineurium, and through the penneurium where the fascicular suture technique is used. The very act of suturing destroys nerve fibers. Only the larger nerves can be sutured without serious damage to axons, and even these require a highly skilled surgeon. Thus, ideally, complete elimination of sutures is desired.

The most critical factor of technique in neurography is the accurate approximation of the cut ends of the fascicles. Even though other factors may be ideal, the neurography will fail if a significant number of fascicles do not match up. This is because motor axons regenerating through the sheaths of sensory nerves and vice versa will give no return of sensory or motor function. The fascicles of the larger nerves, such as the median and ulnar nerve, are large enough in cross sectional area that the cut ends of individual fascicles can be matched up by using the epineural vascular pattern for rotational orientation and microsurgical suture techniques. The fascicles of the small diameter nerves however, are too small to be matched by suturing. The best that can be done is to approx mate the nerve ends using recognizable vascular patterns for correct anatomical alignment. If the peripheral nerve is cleanly and squarely severed. a primary repair can be made with good approxi mation of the fascicles. However if a segmenta deficit exists, the likelihood of surgical orientation or matching of fascicles becomes a matter of chance This is attributed to the twisting and plexiform course of the fascicles and axons within the nerve trunk [3]. It is apparent then, except in the instance of a clean cut followed by a primary repair, that a repair of nerves, successful in all other respects. will depend on the chances that the fascicles will match up, unless some natural mechanism exists for directing the axons to sheaths of their own. I' this regard Peacock reports evidence of rotati›t and reorientation into good anatomical alignment prior to a secondary suture of a nerve previous A joined at a single point of junction, even when the ends were 180° apart when the suture was first placed [21].

The matching fascicles becomes less of a problem with the smaller nerves, since there are fewer fascicles, often no more than one, to contend with. Thus the chief hazard to the successful repair of fine nerves is the trauma produced by sutures and manipulation of the nerve and invasion of the field of regeneration by epineural and extraneural connective tissue. Many attempts have been made, almost entirely with larger nerves, to shield the region of anastomosis from connective tissue and facilitate longitudinal directional growth of the epineural and nervous tissue.

A most recent and promising approach by Millessi dispenses with wrappings altogether, eliminates tension in the field of regeneration, and uses a minimum of sutures [19]. This approach has been extended experimentally to the sciatic nerves of rabbits to the complete elimination of sutures. This technique depends on the use of a graft to eliminate tension and the natural adhesive properties of the nerve ends to hold them in a position of close anatomical approximation. The strength of the union can amount to several grams after the first 15 to 30 minutes, sufficient to prevent separation of the ends and allow closure of the incision [22].

3. Design Requirements for Tubular Nerve Prosthesis

Consideration and understanding of anatomical and functional features, pathophysiology of nerve degeneration and regeneration, and the principles behind current techniques of nerve repair, suggested the following design requirements for a porous thin-walled tube that could, with proper surgical procedures, facilitate nerve repair and regeneration in small diameter nerves:

The tube material must be compatible with its biological environment and be nontoxic. No residual substances must remain after processing that will react deleteriously with the nerve tissue or the biological processes contributing to healing. • The technique of application must facilitate approximation of nerve ends quickly with a minimum of manual manipulation. A method of vacuum approximation has been developed which successfully accomplishes the approximation procedure.

The tube design must incorporate means to remove the tube without damage to the nerve after healing has progressed sufficiently to permit its removal.

• The tube must possess a combination of porosity and wall thickness that imparts to the tube a sufficient degree of permeability to provide adequate diffusion and flow of intraneural and extraneural fluids.

• The tube must possess a combination of porosity and wall thickness that minimizes the surface area of the tube consistent with enough strength to

withstand physical insults. Minimum surface area minimizes the release of toxic substances to the surrounding tissue.

• The pore size of the tube walls must be such as to prevent ingrowth of extraneural connective tissue and, thereby, shield the field of regeneration. • The pore size of the tube must be such as to discourage the ingrowth of intraneural connective tissue and, thereby, avoid the occurrence of adhesions between the inner wall of the porous tube and epineural tissue.

• The tube must possess strength to rigidly support and shield the joined nerve against buckling and crushing by outside as well as internal forces.

The method of fabricating tubes must satisfy the requirements of the models selected for evaluating the efficacy of this method of nerve repair. This method of fabrication must be capable of producing many tubes simultaneously having a uniform size and configuration to a wide range of specifications determined by transverse dimensions and shape of the nerve. A standard size is essential for biostatistical comparison studies of nerve repair parameters.

Essentially, the method employs a porous thinwalled tube similar to that shown in figure 2. A small hole is drilled through one side of each tubular sleeve at the 1/3 point along its length to serve as a vacuum port. The porous tube is fitted snugly into a matching groove in an adapter at the termination of the barrel of the "anastomizer" making a "T" connection with it. (See figs. 3 and 4). The vacuum port in the porous tube is positioned to match the opening at the bottom of the groove in the adapter.

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FIGURE 2. Porous tube having two diametrically opposite long tudinal micro-slots made by a spark discharge machining technique.