Recent Advances and Developments in Neural Repair and Regeneration for Hand Surgery

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RESEARCH ARTICLE

Recent Advances and Developments in Neural Repair and Regeneration for Hand Surgery

The Open Orthopaedics Journal 01 Jan 1970 RESEARCH ARTICLE DOI: 10.2174/1874325001206010103

Abstract

End-to-end suture of nerves and autologous nerve grafts are the ‘gold standard’ for repair and reconstruction of peripheral nerves. However, techniques such as sutureless nerve repair with tissue glues, end-to-side nerve repair and allografts exist as alternatives. Biological and synthetic nerve conduits have had some success in early clinical studies on reconstruction of nerve defects in the hand. The effectiveness of nerve regeneration could potentially be increased by using these nerve conduits as scaffolds for delivery of Schwann cells, stem cells, neurotrophic and neurotropic factors or extracellular matrix proteins. There has been extensive in vitro and in vivo research conducted on these techniques. The clinical applicability and efficacy of these techniques needs to be investigated fully.

Keywords: Conduits, Grafts, Repair, Neurotrophic factors, Schwann cells.

INTRODUCTION

Peripheral nerve injury affecting the upper limbs is a significant problem requiring efficient management in order to avoid disability. The function of the hand is especially dependent on its sensory and motor nerves [1-2]. Some studies have reported that more than 60% of peripheral nerve injuries occur in the upper limbs [1, 3]. These injuries are more common in the dominant hand and occur most commonly in young men [1, 4]. The commonest aetiological factors reported are motor vehicle accidents and sharp objects. The most commonly affected nerves are the ulna, radial and digital nerves [1, 3, 5]. Several new techniques in the management of peripheral nerve injuries such as the use of fibrin glue or nerve conduits have been developed in recent years [6].

ANATOMY

Peripheral nerves conduct information to and from the environment and the central nervous system. Neurons receive signals via dendrites and process them within the cell body. Action potentials are transmitted away from the cell body to targets via axons. Schwann cells surround the axons and provide trophic support. Myelinated nerve fibres have a continuous series of Schwann cells that ensheath individual axons and form myelin. Unmyelinated axons have Schwann cells covering many different axons without creating the myelin layers. Myelin enhances the conduction velocity of action potentials. Peripheral nerve fibres are surrounded by three connective tissue coverings - the endoneurium, the perineurium and the epineurium. The endoneurium surrounds each axon and its Schwann cell layer. The perineurium covers each bundle of peripheral nerve fibres (fascicle). The epineurium is the outermost covering of the nerve and is primarily a protective layer [7, 8].

The hand is supplied by the median, ulnar and radial nerves. The median nerve originates in the brachial plexus and is formed as a branch when the lateral and medial cords join. It enters the hand through the carpal tunnel. Distal to the carpal tunnel the median nerve supplies the first and second lumbricals, opponens pollicis, abductor pollicis brevis and the superficial head of the flexor pollicis brevis. It also provides sensation to the skin of the palmar and distal dorsal aspect of the radial three and a half digits and the adjacent palm. The ulnar nerve arises from the medial cord of the brachial plexus and enters the hand on the volar surface of the flexor retinaculum. The palmar cutaneous branch arises from the ulnar nerve just proximal to the wrist joint and supplies the skin of the medial aspect of the palm. The dorsal cutaneous branch of the ulnar nerve supplies the medial half of the dorsum of the hand, the little finger and the ulnar half of the ring finger. The ulnar nerve divides into superficial and deep branches at the distal border of the flexor retinaculum. The superficial branch supplies the skin on the volar aspect of the little finger and the ulnar half of the ring finger. The deep branch supplies the hypothenar muscles, the third and fourth lumbricals, the adductor pollicis and the dorsal and palmar interossei. The radial nerve arises from the posterior cord of the brachial plexus. The superficial branch of the radial nerve travels deep to the brachioradialis muscle and supplies sensation to the skin of the radial half of the dorsum of the hand and thumb as well as the proximal portions of the dorsal aspects of the radial one and a half digits. Within the hand, the radial nerve does not supply any muscles [8].

CLASSIFICATION OF NERVE INJURIES

Nerve injuries were classified into three types by Seddon in 1943 [9]. The three injury types are neuropraxia, axonotmesis and neurotmesis. Sunderland’s classification in 1951 classified nerve injuries into five degrees which overlap and provide more detail to Seddon’s classification [2, 10].

Neuropraxia (first degree injury) is the mildest form of nerve injury. There is transient conduction block without disruption of the anatomical structure of the nerve. Wallerian degeneration does not occur distal to the injury. Full nerve function is expected without intervention within twelve weeks [2, 9].

Axonotmesis corresponds to second, third and fourth degree injuries. The axons are disrupted and Wallerian degeneration occurs. In second degree injuries, the endoneurim and perineurium are intact and complete regeneration and functional recovery occurs. In third degree injuries, the axon and endoneurium are damaged, but the perineurium and epineurium are intact. This results in disorganized regeneration which can result in obstruction or diversion of axons from their correct paths. Fourth degree injuries involve damage to all structures, however, continuity of the nerve trunk is bridged by a mass of connective tissue, Schwann cells and regenerating axons. Conduction down the nerve is not possible [2, 9, 10].

Neurotmesis (fifth degree injury) is complete division of the nerve. In addition to this, a sixth degree of injury has been described by MacKinnon [11]. This refers to lesions with a mixed pattern of injury where there are varying degrees of injury in different sections of the nerve [12].

PATHOPHYSIOLOGY OF NERVE REGENERATION

Wallerian degeneration is a sequence of cellular events which occurs in the distal segment of a nerve fibre after injury that has resulted in loss of axonal continuity [13]. The axons disintegrate, undergo apoptosis and release vesicles of cytosol and organelles [7]. The debris is cleared by Schwann cells and macrophages that migrate across local vessels and create long, clean endoneurial tubes. The Schwann cells proliferate and grow in ordered columns along the endoneurial tube to form bands of Büngner. This provides a clear pathway for directed axonal regeneration [7, 14].

Within 24 to 48 hours, axonal sprouts form at the proximal stump and grow on the surface of Schwann cells or to the inner surface of the basal lamina of the bands of Büngner. If the proximal and distal segments are apposed, the axonal sprouts may grow until they enter the distal stump. If the axonal sprouts do not elongate through the distal Schwann cell tube, they will grow in a more random manner which may lead to neuroma formation [14]. Additionally, axonal regeneration is regulated by various factors molecules including neurotrophic and neurotropic factors, cell adhesion molecules and extracellular matrix proteins [15, 16].

DIAGNOSIS OF NERVE INJURIES

A thorough knowledge of the anatomy of the nerve as as well as the muscles and zones of sensation supplied by the nerve is essential in making an accurate diagnosis [17]. The first step in diagnosing a nerve injury in the hand is to take an accurate thorough history from the patient. This should include the patient’s age, occupation, hand dominance, hobbies, mechanism of injury and past medical history. The physical examination should include a sensory and motor assessment of each nerve comparing the findings with the contralateral side. The sensory evaluation should include two point discrimination [2]. The motor assessment should include power and range of motion. Palpation or inspection of the muscle belly under consideration is useful to avoid inaccuracy of assessment due to substitution or trick movement [17]. The Tinel sign can be used to localise the nerve injury. A positive Tinel sign suggests that regenerating axonal sprouts that have not obtained complete myelinization are progressing along the endoneurial tube. Electrodiagnostic tests may be performed if the clinical findings are unclear and to diagnose the injury and determine the severity [2, 17].

CONVENTIONAL SURGICAL TREATMENT OF NERVE INJURIES

Fourth to sixth degree injuries have a poor prognosis for recovery of function without surgical intervention. Repair of sixth degree injuries is particularly challenging due to the risk of disrupting fibres with first to third degree injuries whilst attempting to correct areas of fourth and fifth degree injury [17].

End-to-End Nerve Suture

Apposition of the nerve ends and repair by suturing should be possible if there has been a sharp clean transection and exploration is undertaken within 72 hours. It is advisable to delay repair by two to three weeks in the case of blunt transection. At this stage it will be possible to determine the amount of stump resection that is required to achieve healthy nerve tissue [18]. Nerve suture should be performed using an atraumatic microsurgical technique using an operating microscope and 10-0 monofilament suture material [2]. The lesion is repaired using epineurial or perineurial sutures. Epineurial repair results in approximation of the nerve ends, however fascicular coaptation is often poor and this may result in a reduced number of axons regenerating across the junction due to problems such as internal gaps, overlapping and buckling of the fascicles [19]. Perineurial suturing allows fascicles/groups of fascicles to be repaired in an attempt to achieve more accurate axonal alignment. However, the increased dissection required for this approach could potentially result in increased scarring and damage to the blood supply [19, 20]. There is little clinical evidence that perineurial repair results in superior clinical outcomes to epineurial repair [20, 22]. Techniques to facilitate fascicular matching include intraoperative nerve stimulation and staining of nerve ends with blue SAb, carbonic anhydrase and cholinesterase for example [12].

Autologous Nerve Grafting

Nerve grafting is indicated if primary end-to-end closure of the two transected nerve ends is not possible without excessive tension. Terzis et al., compared suturing of rat sciatic nerve under varying degrees of tension to nerve grafting and showed that superior conduction velocities and amplitudes of evoked potentials were achieved with nerve grafting than with nerve suturing under excessive tension [23]. A section of nerve can be harvested and placed between the two nerve ends. Autologous nerve grafts are considered the ‘gold standard’ [18]. Suitable donor sites for autologous nerve grafts include the sural nerve, anterior branch of the medial antebrachial cutaneous nerve the lateral femoral cutaneous nerve and the superficial radial nerve. The graft should be approximately 10 to 20% longer than the defect to be grafted in order to overcome the effect of connective tissue fibrosis. Several grafts may need to be placed in parallel to reconstruct the nerve if it has a large diameter relative to the graft obtained [20]. A series of interfascicular autologous nerve grafting by Millesi et al., reported useful motor recovery in 82% of 38 patients after median nerve grafting and 37 out of the 38 regained protective sensibility. 100% of 39 patients who underwent ulnar nerve grafting and 77% of 13 patients with radial nerve lesions regained useful motor recovery. The cases with poor results were generally found to be associated with the presence of unfavourable factors such as advanced age, severity of original trauma and a long time interval before repair [24]. Other studies have shown that patient age, width of contusion and length of time before surgery have significant effects on both nerve repair and reconstruction with grafting [25-27].

An appropriate blood supply is required for successful nerve grafting. Revascularization of a nerve graft may occur by vessels from the surrounding tissue bed growing into the nerve graft or by vessels from the end of the graft sprouting into the existing vascular tree [28]. Free nerve grafts may be hindered by delayed establishment of blood supply to the nerve graft leading to fibrosis, development of central necrosis and finally failure of nerve regeneration [23]. Vascularized nerve grafts may be used to avoid this. However, the procedure is time-consuming and it may be difficult to obtain a suitable, well-vascularized expendable donor. Taylor recommended that vascularized nerve grafts are only used when there is a high risk of graft necrosis. It may be considered in situations where the nerve gap is large, the recipient bed is scarred, or the free transfer of a thick nerve is desired [29, 30]. A study of 151 vascularized ulnar nerve grafts performed over a period of 23 years reported better outcomes when compared to conventional nerve grafts. The best outcomes were observed for pedicled ipsilateral nerve grafts for single targets [28].

RECENT ADVANCES IN PERIPHERAL NERVE REPAIR

Sutureless Nerve Repair

Peripheral nerve suture may be complicated by foreign-body inflammatory reaction leading to impaired nerve regeneration [6, 31]. A variety of tissue glues or laser to perform sutureless nerve repair have therefore been investigated as an alternative. The use of cryanoacrylate glue, for example, has been tested, but was unsuccessful as it also caused a foreign-body reaction and fibrosis [32]. Fibrin glue, which is more biocompatible than cryanoacrylate has shown more promising results [6, 31]. Ornelas et al., compared the use of bovine and human fibrin glues to microsutures for repair of rat median nerves. They showed that nerve repairs performed using fibrin glues were quicker and technically easier to perform and were associated with less inflammatory response and fibrosis. Additionally, the fibrin glue repairs resulted in better axonal regeneration and fibre alignment [33]. Laser-activated protein solders containing bovine serum albumin have also been successfully used for sutureless peripheral nerve repair in rats and have been tested as an alternative to fibrin glue as they result in a greater adhesion strength [31, 34, 35]. A chitosan-based laser-activated adhesive has also been shown to produce successful sutureless anastomosis in vivo in rat tibial nerves. The activation temperature range of the the chitosan-based adhesive is around 5C lower than for albumin solders and it has been proposed that consequently there may be a reduced risk of tissue thermal damage [31]. Borzorg et al., carried out a clinical study of the use of fibrin glue for facial nerve repair and reported good results after a mean follow-up period of 50 months [36]. However, long-term clinical evidence of sutureless peripheral nerve repair in hand surgery in humans is needed.

End-to-Side Nerve Repair

End-to-side nerve repair is an approach which has been used in cases where the proximal stump is not available (for example in cases where it is very distant from the distal stump). The distal stump is coapted to the side of an intact donor nerve. The donor nerve does not lose any function. The potential advantage of this technique is that donor site morbidity associated with nerve graft harvest is avoided and the distance travelled by regenerating axons is reduced [37]. However, experimental studies have produced mixed results with some studies demonstrating only limited motor or sensory recovery [38-40]. More research is needed before this approach can be considered an established technique of nerve repair [37].

Nerve Allografts and Xenografts

Autologous nerve grafting may be complicated by donor site morbidity such as scarring, neuroma formation and sensory loss in the distribution of the donor nerve [41]. There may also be an insufficient amount of expendable autologous nerve available for large nerve defects [42]. Nerve allografts and xenografts act as a temporary scaffold across which host axons regenerate [6]. Due to the risk of rejection, the use of appropriate immunosupression is essential [43]. The allograft tissue is eventually completely replaced by the host tissue once regeneration has occurred. At this stage, immunosuppression may be discontinued. The immunosuppressant tacrolimus (FK 506) has shown neuroregenerative and neuroprotective effects whilst simultaneously acting as an effective immunosuppressant [6, 41]. Clinical evidence on the efficacy of allografts/xenografts is scarce. However, some early clinical studies of nerve allografts have however shown some success in achieving return of motor function or sensation [41-44].

Nerve Conduits

Nerve conduits provide a channel for direction of axonal sprouts from the proximal stump to the distal nerve stump. In addition to this, they allow diffusion of neurotrophic and neurotropic factors secreted by the Schwann cells of the distal stump and minimize infiltration of fibrous tissue [6]. Animal models in rats as well as cats and primates, have shown successful nerve regeneration with the use of nerve conduits fabricated from a variety of synthetic materials (e.g. polyglycolic acid, silicon, glycolide trimethylene carbonate, polylactide-co-caprolone) and biological materials (e.g. collagen, laminin, silk, autogenous vein/ muscle grafts) [21, 45-50]. The clinical evidence of efficacy of nerve conduits is more limitied. Mackinnon and Dellon conducted an early clinical study of the use of polyglycolic acid conduits for digital nerves with nerve gaps of up to 3cm and reported excellent or good functional sensation in 86% of patients [51]. Lohmeyer et al., reported excellent results with collagen conduits for nerve gaps in the hand of up to 18mm in 4 out of 6 patients [52]. Bushnell et al., reported good or excellent function in 8 out of 9 patients who had undergone digital nerve repair with a collagen nerve tube at one year follow-up [53]. Weber et al., performed a randomized prospective study of polyglycolic acid conduits for digital nerve reconstruction compared to conventional nerve repair or grafting. 98 patients with 136 nerve transections were included in the study. The overall results showed no significant difference in outcome between the two groups in general. However, improved sensation was found with the polyglycolic acid nerve conduits for nerve gaps of 4mm or less compared to conventional repair or grafting of digital nerves [54].

Molecular and Cell Therapy

Experimental studies have shown that the use of conduits seeded with cultured Schwann cells improve nerve regeneration [55-57]. The use of fetal and adult progenitor neuronal cells and bone-marrow stem cells is an alternative to the use of Schwann cells. Cell therapy is limited by the technical and logistical difficulties in culturing and expanding these cells in vitro [55]. Another approach that has been studied is the incorporation of neurotrophic and neurotropic factors e.g. nerve growth factor, brain derived neurotrophic factor and ciliary neurotrophic factor etc into nerve conduits in order to improve the regeneration process [7, 12]. The effect of extracellular matrix molecules such as fibronectin, laminin and hyaluronic acid on axonal regeneration as well as the effect of incorporating these proteins into nerve conduits has also been investigated [7, 58-61]. The use of these techniques has been largely experimental to date.

CONCLUSION

The current standard treatment for peripheral nerve injuries of the hand is end-to-end repair with epineurial sutures. End-to-side nerve suturing may be considered when the proximal stump is unavailable. However, studies of end-to-side repair have shown mixed results. Studies on sutureless nerve repair using fibrin glues or laser-activated protein or chitosan-based materials have produced some promising results. Nerve grafting is indicated if suture repair is not possible without excessive tension. As autologous nerve grafting may be associated with donor site morbidity, alternatives such as the use of allografts with appropriate immunosuppression has been sought. Research into the use of nerve conduits is in progress and has shown some success. Molecular and cell therapy is another area which has the potential to improve the future of nerve regeneration. More clinical trials are required to assess these techniques.

CONFLICT OF INTEREST

None declared.

ACKNOWLEDGEMENT

None declared.

REFERENCES

1
Eser F, Aktekin LA, Bodur H, Atan C. Etiological factors of traumatic peripheral nerve injuries Neurol India 2009; 57: 434-7.
2
Berger A, Mailänder P. Advances in peripheral nerve repair in emergency surgery of the hand World J Surg 1991; 15: 493-500.
3
Noble J, Munro CA, Prasad VS, Midha R. Analysis of upper and lower extremity peripheral nerve injuries in a population of patients with multiple injuries J Trauma 1998; 45: 116-22.
4
McAllister RM, Gilbert SE, Calder JS, Smith PJ. The epidemiology and management of upper limb peripheral nerve injuries in modern practice J Hand Surg Br 1996; 21: 4-13.
5
Kouyoumdjian JA. Peripheral nerve injuries a retrospective survey of 456 cases Muscle Nerve 2006; 34: 785-8.
6
Bhandari PS, Sadhotra LP, Bhargava P, et al. What is new in peripheral nerve repair? Indian J Neurotrauma 2007; 4: 21-3.
7
Kang JR, Zamorano DP, Gupta R. Limb salvage with major nerve injury: current management and future directions J Am Acad Orthop Surg 2011; 19(Suppl 1): S28-34.
8
Moore KL, Dalley AF. Clinically Oriented Anatomy 4th. 1999; 774-.
9
Seddon HJ. Three types of nerve injury Brain 1943; 66: 237-88.
10
Sunderland S. A classification of peripheral nerve injuries producing loss of function Brain 1951; 74: 491-516.
11
Mackinnon SE, Dellon AL. Classification of nerve injuries as the basis for treatment In: Mackinnon SE, Ed. Surgery of the peripheral nerve 1988; 35-63.
12
Evans GR. Peripheral nerve injury: a review and approach to tissue engineered constructs Anat Rec 2001; 263: 396-404.
13
Chaudhry V, Cornblath DR. Wallerian degeneration in human nerves: serial electrophysiological studies Muscle Nerve 1992; 15: 687-93.
14
Radtke C, Vogt PM. Peripheral nerve regeneration: a current perspective Eplasty 2009; 12(9 ): e47.
15
Mackinnon SE, Dvali LT. Basic pathology of the hand wrist and Forearm nerve In: Berger RA, Weiss APC, Eds. Hand surgery. Philadelphia: Lipincott Williams and Wilkins 2004; pp. 37-49.
16
Raivich G, Kreutzberg GW. Peripheral nerve regeneration role of growth factors and their receptors Int J Dev Neurosci 1993; 11: 311-24.
17
Jobe MT, Martinez SF. Peripheral nerve injuries In: Canale ST, Ed. Campbell s operative orthopaedics 11th. 2007; 59pp: 3636-707.
18
Sulaiman WA, Kline DG. Nerve surgery: a review and insights about its future Clin Neurosurg 2006; 53: 38-47.
19
Marshall DM, Grosser M, Stephanides MC, Keeley RD, Rosen JM. Sutureless nerve repair at the fascicular level using a nerve coupler J Rehabil Res Dev 1989; 26: 63-76.
20
Lee SK, Wolfe SW. Peripheral nerve injury and repair J Am Acad Orthop Surg 2000; 8: 243-52.
21
Lundborg G, Rosén B, Dahlin L, Danielsen N, Holmberg J. Tubular versus conventional repair of median and ulnar nerves in the human forearm early results from a prospective randomized clinical study J Hand Surg Am 1997; 22: 99-106.
22
Orgel MG. Epineurial versus perineurial repair of peripheral nerves Clin Plast Surg 1984; 11: 101-4.
23
Terzis JK, Skoulis TG, Soucacos PN. Vascularized nerve grafts. A review Int Angiol 1995; 14: 264-77.
24
Millesi H, Meissl G, Berger A. Further experience with interfascicular grafting of the median, ulnar, and radial nerves J Bone Joint Surg Am 1976; 58: 209-18.
25
Vastamäki M, Kallio PK, Solonen KA. The results of secondary microsurgical repair of ulnar nerve injury J Hand Surg Br 1993; 18: 323-6.
26
Kallio PK, Vastamäki M, Solonen KA. The results of secondary microsurgical repair of radial nerve in 33 patients J Hand Surg Br 1993; 18: 320-2.
27
Kallio PK, Vastamäki M. An analysis of the results of late reconstruction of 132 median nerves J Hand Surg Br 1993; 18: 97-105.
28
Terzis JK, Kostopoulos VK. Vascularized ulnar nerve graft: 151 reconstructions for posttraumatic brachial plexus palsy Plast Reconstr Surg 2009; 123: 1276-91.
29
Taylor GI. Nerve grafting with simultaneous microvascular reconstruction Clin Orthop Relat Res 1978; 133: 56-70.
30
Jobe MT. Microsurgery In: Canale ST, Ed. Campbell's operative orthopa. 11th. Philadelphia: Mosby Elsevier 2007; 60: pp. 3708-99.
31
Lauto A, Foster LJ, Avolio A, et al. Sutureless nerve repair with laser-activated chitosan adhesive: a pilot in vivo study Photomed Laser Surg 2008; 26: 227-34.
32
Wieken K, Angioi-Duprez K, Lim A, Marchal L, Merle M. Nerve anastomosis with glue: comparative histologic study of fibrin and cyanoacrylate glue J Reconstr Microsurg 2003; 19: 17-20.
33
Ornelas L, Padilla L, Di Silvio M, et al. Fibrin glue: an alternative technique for nerve coaptation--Part II. Nerve regeneration and histomorphometric assessment J Reconstr Microsurg 2006; 22: 123-8.
34
Lauto A, Dawes JM, Piper JA, Owen ER. Laser nerve repair by solid protein band technique. II: assessment of long-term nerve regeneration Microsurgery 1998; 18: 60-4.
35
Lauto A, Dawes JM, Cushway T, Piper JA, Owen ER. Laser nerve repair by solid protein band technique. I: identification of optimal laser dose, power, and solder surface area Microsurgery 1998; 18: 55-9.
36
Bozorg Grayeli A, Mosnier I, Julien N, et al. Long-term functional outcome in facial nerve graft by fibrin glue in the temporal bone and cerebellopontine angle Eur Arch Otorhinolaryngol 2005; 262: 404-7.
37
Pannucci C, Myckatyn TM, Mackinnon SE, Hayashi A. End-to-side nerve repair: review of the literature Restor Neurol Neurosci 2007; 25: 45-63.
38
Tarasidis G, Watanabe O, Mackinnon SE, et al. End-to-side neurorraphy: a long-term study of neural regeneration in a rat model Otolaryngol Head Neck Surg 1998; 119: 337-41.
39
Tarasidis G, Watanabe O, Mackinnon SE, et al. End-to-side neurorrhaphy resulting in limited sensory axonal regeneration in a rat model Ann Otol Rhinol Laryngol 1997; 106: 506-12.
40
Jaeger MR, Braga-Silva J, Gehlen D, et al. End-to-end versus end-to- side motor and sensory neurorrhaphy in the repair of the acute muscle denervation Ann Plast Surg 2011; 67: 391-6.
41
Mackinnon SE, Doolabh VB, Novak CB, Trulock EP. Clinical outcome following nerve allograft transplantation Plast Reconstr Surg 2001; 107: 1419-29.
42
Siemionow M, Sonmez E. Nerve allograft transplantation: a review J Reconstr Microsurg 2007; 23: 511-20.
43
Kvist M, Sondell M, Kanje M, Dahlin LB. Regeneration in and properties of extracted peripheral nerve allografts and xenografts J Plast Surg Hand Surg 2011; 45: 122-8.
44
Karabekmez FE, Duymaz A, Moran SL. Early clinical outcomes with the use of decellularized nerve allograft for repair of sensory defects within the hand Hand (NY) 2009; 4: 245-9.
45
Chiu DT, Janecka I, Krizek TJ, Wolff M, Lovelace RE. Autogenous vein graft as a conduit for nerve regeneration Surgery 1982; 91: 226-33.
46
Mackinnon SE, Dellon AL. A study of nerve regeneration across synthetic (Maxon) and biologic (collagen) nerve conduits for nerve gaps up to 5 cm in the primate J Reconstr Microsurg 1990; 6: 117-21.
47
Waitayawinyu T, Parisi DM, Miller B, et al. A comparison of polyglycolic acid versus type 1 collagen bioabsorbable nerve conduits in a rat model: an alternative to autografting J Hand Surg Am 2007; 32: 1521-9.
48
Kitahara AK, Nishimura Y, Shimizu Y, Endo KJ. Facial nerve repair accomplished by the interposition of a collagen nerve guide J Neurosurg 2000; 93: 113-20.
49
Li ST, Archibald SJ, Krarup C, Madison RD. Peripheral nerve repair with collagen conduits Clin Mater 1992; 9: 195-200.
50
Nectow AR, Marra KG, Kaplan DL. Biomaterials for the Development of Peripheral Nerve Guidance Conduits Tissue Eng Part B Rev 2011 Sep 23; [Epub ahead of print]
51
Mackinnon SE, Dellon AL. Clinical nerve reconstruction with a bioabsorbable polyglycolic acid tube Plast Reconstr Surg 1990; 85: 419-24.
52
Lohmeyer J, Zimmermann S, Sommer B, et al. [Bridging peripheral nerve defects by means of nerve conduits] Chirurg 2007; 78: 142-7.
53
Bushnell BD, McWilliams AD, Whitener GB, Messer TM. Early clinical experience with collagen nerve tubes in digital nerve repair J Hand Surg Am 2008; 33: 1081-7.
54
Weber RA, Breidenbach WC, Brown RE, Jabaley ME, Mass DP. A randomized prospective study of polyglycolic acid conduits for digital nerve reconstruction in humans Plast Reconstr Surg 2000; 106: 1036-45.
55
Chong AK, Chang J. Tissue engineering for the hand surgeon: a clinical perspective J Hand Surg Am 2006; 31: 349-58.
56
Tohill M, Terenghi G. Stem-cell plasticity and therapy for injuries of the peripheral nervous system Biotechnol Appl Biochem 2004; 40: 17-24.
57
Hadlock T, Elisseeff J, Langer R, Vacanti J, Cheney M. A tissue-engineered conduit for peripheral nerve repair Arch Otolaryngol Head Neck Surg 1998; 124: 1081-6.
58
Martini R. Expression and functional roles of neural cell surface molecules and extracellular matrix components during development and regeneration of peripheral nerves J Neurocytol 1994; 23: 1-28.
59
Williams LR, Danielsen N, Müller H, Varon S. Exogenous matrix precursors promote functional nerve regeneration across a 15-mm gap within a silicone chamber in the rat J Comp Neurol 1987; 264: 284-90.
60
Madison RD, da Silva C, Dikkes P, Sidman RL, Chiu TH. Peripheral nerve regeneration with entubulation repair: comparison of biodegradeable nerve guides versus polyethylene tubes and the effects of a laminin-containing gel Exp Neurol 1987; 95: 378-90.
61
Seckel BR, Jones D, Hekimian KJ, et al. Hyaluronic acid through a new injectable nerve guide delivery system enhances peripheral nerve regeneration in the rat J Neurosci Res 1995; 40: 318-24.