|Year : 2016 | Volume
| Issue : 2 | Page : 72-76
Update in facial nerve paralysis: tissue engineering and new technologies
Mohamed A Elsayed1, Ahmed M.M. Elrefai1, Ahmed A Abd Elfattah2
1 Department of Otorhinolaryngology, Faculty of Medicine, Benha University, Benha, Egypt
2 Department of Otorhinolaryngology, Imbaba, Giza Governorate, Egypt
|Date of Submission||14-Feb-2016|
|Date of Acceptance||11-Jul-2016|
|Date of Web Publication||1-Mar-2017|
Ahmed A Abd Elfattah
Master degree, Meet Tarif, Dekernis, 35787, Dakahliya Governorate
Source of Support: None, Conflict of Interest: None
The facial nerve is one of the most commonly injured cranial nerves. Paralysis of the facial nerve is a cause of considerable functional and aesthetic disfigurement. Here, we review recent developments in the management of facial nerve paralysis and in facial reanimation restoring both form and function. We also discuss tissue engineering and new technologies and their role in the treatment of facial nerve paralysis.
Keywords: facial nerve paralysis, new technologies, tissue engineering
|How to cite this article:|
Elsayed MA, Elrefai AM, Abd Elfattah AA. Update in facial nerve paralysis: tissue engineering and new technologies. Benha Med J 2016;33:72-6
|How to cite this URL:|
Elsayed MA, Elrefai AM, Abd Elfattah AA. Update in facial nerve paralysis: tissue engineering and new technologies. Benha Med J [serial online] 2016 [cited 2017 Jun 28];33:72-6. Available from: http://www.bmfj.eg.net/text.asp?2016/33/2/72/201281
| Introduction|| |
Facial paralysis is not an uncommon problem, and the annual incidence has been estimated to be ∼70 cases per 100 000 population. Peripheral facial paralysis remains a diagnostic challenge. Every effort must be made to determine the cause so that appropriate treatment can be initiated .
The imaging of bony structures is preferably performed with computed tomography. MRI has a superior soft-tissue contrast to computed tomography that enables imaging of the facial nerve itself. Therefore, the normal facial nerve is readily visualized from the brain stem, passing through the cerebellopontine cistern and the internal auditory canal to the fundus with T2-weighted and T1-weighted sequences with high spatial resolution .
Most of the larger centers use facial nerve monitoring routinely, and continuous monitoring intraoperatively is recommended . The decision to use facial nerve monitoring when operating in the middle ear is surgeon dependent .
Routine use of facial nerve monitoring was shown to be more cost-effective than selective use of facial monitoring combined with the management of complications of facial nerve injury in cases of nonuse .
Other surgeons elect to use facial nerve monitoring only in situations of chronic or recurrent middle-ear disease. Patients with chronic ear disease, cholesteatoma, and patients with prior surgery may have obscured/absent anatomic landmarks. In these cases, facial nerve monitoring may allow the surgeon to dissect with greater safety in the midst of cholesteatoma, granulation tissue, and fibrosis ,.
Management of facial nerve paralysis
Studies confirm the efficacy of steroids and suggest potential additional benefits of antivirals. However, the evidence regarding the timing and dosage of these agents is less conclusive .
Although there are many clinicians who endorse surgical intervention in a selected patient population  there are others who feel surgery is never indicated in Bell’s palsy .
Fisch  recommended decompression when the patient reaches 90% degeneration on electroneuronography but Adour  saw no difference in recovery of function following surgery in patients with electroneuronography denervation >90% when compared with steroids alone.
Direct coaptation of the transected nerve ends offers the best hope for satisfactory recovery of facial function. Intratemporal facial nerve defects up to 17 mm in length can be repaired directly by extensive mastoid and extratemporal rerouting of the facial nerve. If primary nerve repair results in tension across the site of coaptation, even after proximal and distal mobilization of the severed nerve ends, a nerve graft is mandatory .
Reinnervation techniques are indicated in two situations. The first is when the proximal facial nerve stump is not available, but where the distal facial nerve and facial musculature are present and functional. The second situation occurs following skull base surgery, intracranial injury, or traumatic facial paralysis, when the nerve is thought to be anatomically intact but there is no discernible return of function after a satisfactory waiting period of 12 months .
VII–VII cross-face nerve grafting possesses the major advantage of spontaneous return of function and can produce true emotion-based expression (emotive smile) , but donor branches contain fewer motor axons compared with the hypoglossal nerve, leading most surgeons to feel that the motor power provided by the hypoglossal nerve is distinctly superior .
Facial reanimation using muscle transposition should be considered when the distal neuromuscular unit is either absent, nonviable due to fibrosis, or in congenital facial paralysis. Additionally, there may be significant soft-tissue defects after tumor extirpation that are amenable to defect repair with a regional muscle or microneurovascular free tissue transfer that acts secondarily to reanimate the face .
Reinnervation of free muscle transfers by anastomosis to the proximal stump of the facial nerve can result in a spontaneous, albeit synkinetic smile. This potential for reinnervation is an advantage over temporalis muscle transfer. Free flaps are often not the first choice in facial reanimation because of the length of operating time and necessary microvascular expertise .
The nerve-to-masseter muscle has the advantage of single-stage surgery, on the same side of the face, and this motor nerve provides a stronger contraction of the gracilis muscle, thereby creating greater excursion of the commissure and a bigger smile. The downside is that the smile created is not spontaneous and requires some learning for the patient to make it appear natural. The cross-face nerve graft has the advantage of a totally spontaneous smile without the need for learning or practice. Its disadvantages are two stages separated by many months, donor site scars on the face and leg with numbness of the lateral foot (if the sural nerve is used), and risk to the intact facial nerve .
Tissue engineering and new technologies
Tissue engineering is the use of living cells, biomolecules, and/or biomaterials to provide a better, alternative means of treatment for tissue and organ damage by combining both biologic and artificial components in such a way that a long-lasting repair is produced .
The main pillars of tissue engineering are (a) microsurgery, (b) cell and tissue transplantation, (c) material science, and (d) gene transfer .
Microsurgery: Microsurgery is the key scientific discipline in nerve tissue engineering, not only because it represents the last step for most clinical applications but also because it should give directions to the other disciplines to avoid the production of ‘sterile’ basic science results .
Cell and tissue transplantation: Much focus has been dedicated to the employment of Schwann cells as these cells play a pivotal role in peripheral nerve regeneration forming the bands of Büngner to direct regenerating axons across the lesion site and releasing neurotrophic factors ,.
Many studies have shown that a vein conduit filled with Schwann cells allows successful bridging of rabbit nerve defects up to 40 and 60 mm ,.
Another option for cell transplantation in peripheral nerves is the use of mesenchymal stem cells (MSCs) as they can be easily obtained, purified, and expanded in culture, offering a potentially unlimited source of cells for tissue engineering ,. Another advantage of MSCs is that they can be obtained from various adult stem cell niches, such as bone marrow, adipose tissue, tooth pulp, and umbilical cord blood. MSCs are thought to be able to differentiate into multiple cell lineages, including neuron-like and glial-like cells ,, and it has been shown that human MSCs can be differentiated into neural cells in vitro and transplanted into the injured facial nerve of the guinea pig for improving nerve regeneration .
Although the efficacy of monotissue vein and muscle conduits has been proven both experimentally and with patients, its effectiveness is usually limited to reconstruction of short nerve gaps ,. In fact, the vein tends to collapse and axon dispersion occurs when muscle autografts alone are used to bridge long nerve gaps. For this reason, studies have been conducted to investigate the possibility of engineering a combined conduit by enriching vein segments with fresh skeletal muscle fibers to improve the effectiveness of tubulization nerve repair. The original rationale of the muscle–vein-combined approach was that muscle enrichment prevents vein collapse while the vein wall prevents axon dispersion ,.
Materials for nerve repair: Various materials have been studied to prepare nerve conduits of either synthetic or natural products . Both nondegradable and (bio)degradable materials have been used for NGC fabrication .
- Nondegradable materials for nerve guides:
Silicone NGCs have been widely used to study the effect of different types of guide fillers, particularly ECM analogs, on axonal elongation .
Nonresorbable expanded polytetrafluoroethylene (GoreTex; W. L. Gore & Associates, Inc., 555 Paper Mill Road Newark, DE 19711, U.S.A.) nerve guides were implanted into five patients aged 16–56 years to bridge lesions 2–15 mm in length in different facial nerves. Implantations were performed 4–30 months after the initial trauma had occurred. Three years later, postoperative assessment revealed recovery in two patients .
Disadvantages of the use of nondegradable artificial nerve guides are chronic foreign body reaction, inflexibility, and lack of stability .
- Biodegrabable synthetic materials for nerve guides:
Recent research has been focused on the production of biodegradable artificial nerve guides, which degrade within a reasonable period and only show mild foreign body reaction. Biodegradable materials offer several advantages, such as the possibility of incorporating stem cells or bioactive molecules through physicochemical modifications of the polymers and delivering them during biodegradation. Another interesting property is their flexibility, as variations in their chemical or engineering properties may change biocompatibility, degradation behavior, porosity, and mechanical strength .
Neurotube (Synovis Micro Companies Alliance, Inc., 439 Industrial Lane Birmingham, Alabama, U.S.A.) is a woven polyglycolic acid tube prepared with an external corrugation for wall strength. Its permeability permits the exchange of nutrients and oxygen, creating an ideal environment for neurotrophic mobility. Neurotube is useful for the reconstruction of facial nerve lesions with a small nerve gap (<3 cm) when a direct anastomosis of the two stumps is not possible, or when the suture appears to be in tension. It is a valid alternative to autologous and biological tubularized grafts. The limits of this method are as follows: (a) it can only be used with gaps of less than 3 cm; (b) it is quite costly; (c) there are reports of possible intolerance; and (d) it is not suitable for lesions of the proximal part of the facial nerve because of its dimensions (40×23 mm) .
- Natural polymers for nerve guides:
Natural polymers are advantageous materials for tissue engineering of nerves as they are biocompatible, favor the migration of supporting cells, and avoid the occurrence of toxic effects. In some cases, blends between natural and synthetic polymers have been proposed for NGCs, to combine the biocompatibility of the natural component with the advantageous processing properties and mechanical performance of the synthetic material .
Excellent facial nerve regeneration was achieved by interposition of a collagen nerve guide in a 5-mm nerve gap in adult cats, demonstrating great promise for the collagen nerve guide as a nerve conduit. This excellent performance of the collagen nerve guide in a 5-mm nerve gap in adult cats can be speculated to correspond to similar placement in a 10–20-mm gap in humans .
Recently, nerve guidance channels consisting of Chitosan conduits filled with porous collagen sponges simulating the three-dimensional structure of the extracellular matrix have been obtained. The inner sponge was imbibed with nerve growth factor. Conduits have been tested for the repair of a 10 mm defect in the rabbit facial nerve: in one case, a suspension of neural stem cells was injected into the tube during in-vivo implantation, whereas in the control test a saline solution was used. Autograft was used as a positive control. Twelve weeks after implantation, nerves treated with autografts showed similar recovery as compared with the ones treated with nerve guidance channels containing neural stem cells .
Processed nerve allografts have shown promise in numerous animal studies and in early clinical explorations. While processed nerve allografts are acellular, they contain many of the beneficial characteristics of the nerve autograft, such as physical macrostructures, three-dimensional microstructural scaffolding, and protein components inherent to nerve tissue .
Nanotechnology and tissue engineering
Nanotechnology could finally solve the numerous problems associated with traditional implants, by mimicking the properties of natural tissues. Progress in nanotechnology provides a platform to develop novel and improved neural tissue engineering synthetic materials, including designing nanofiber/nanotube scaffolds with excellent cytocompatibility, conductivity properties to boost neuron activities, and in some cases able to encapsulate neural stem cells and Schwann cells into biomimetic scaffolds to enhance nerve repair .
New technologies for management of facial paralysis
Many proposed strategies for restoring function in facial paralysis patients require a direct neural interface. One application of the interface lies in recording from intact neural tissue. For example, in a patient with unilateral paralysis or synkinesis, one could extract intricate neural signals from the normal side for the treatment of contralateral impairment. The second application involves electrically stimulating interfaced nerves for functional restoration. In this case, the interface is used to modify the activity of the nerve, thereby inducing muscle contraction to restore movement .
| Conclusion|| |
Advances in surgical technique, tissue engineering, bioelectrical interfaces, and nanotechnology hold promise for the successful treatment of facial nerve paralysis.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Kosins AM, Hurvitz KA, Evans GR, Wirth GA. Facial paralysis for the plastic surgeon. Can J Plast Surg 2007; 15:77–82.
Jäger L, Reiser M. CT and MR imaging of the normal and pathologic conditions of the facial nerve. Eur J Radiol 2001; 40:133–146.
Mohorikar AV. Testing of the facial nerve. In: Grewal DS, editor. Atlas of surgery of the facial nerve: an otolaryngologist’s perspective
, 2nd ed. New Delhi, India: Jaypee Brothers Medical Publishers; 2012; 23–29.
Silverstein H, Smouha EE, Jones R. Routine intraoperative facial nerve monitoring during otologic surgery. Am J Otol 1988; 9:269–275.
Wilson L, Lin E, Lalwani A. Cost‐effectiveness of intraoperative facial nerve monitoring in middle ear or mastoid surgery. Laryngoscope 2003; 113:1736–1745.
Leonetti JP, Smith PG, Matz GJ, Beck DL. Facial nerve monitoring in otologic surgery: clinical indications and intraoperative technique. Ann Otol Rhinol Laryngol 1990; 99:911–918.
Vrabec JT. Medical treatment of Bell’s palsy. In: Slattery WH, editor. The facial nerve, 1st ed. New York, USA: Thieme; 2014; 81–88.
Yanagihara N, Hato N, Murakami S, Honda N. Transmastoid decompression as a treatment of Bell palsy. Otolaryngol Head Neck Surg 2001; 124:282–286.
Adour KK. Decompression for Bell’s palsy: why I don’t do it. Eur Arch Otrhinolaryngol 2002; 259:40–47.
Fisch U. Surgery for Bell’s palsy. Arch Otolaryngol 1981; 107:1–11.
Anderson RG. Facial nerve disorders and surgery. Select Read Plast Surg 2001; 9:1–39.
Henstrom DK, Hadlock TA. Facial nerve repair. In: Slattery WH, editor. The facial nerve
. 1st ed. New York, USA: Thieme; 2014; 179–191.
Scaramella L. Cross-face facial nerve anastomosis: historical notes. Ear Nose Throat J 1996; 75:343–354.
Glickman L, Simpson R. Cross-facial nerve grafting for facial reanimation: effect on normal hemiface motion. J Reconstr Microsurg 1996; 12:201–202.
Tate JR, Tollefson TT. Advances in facial reanimation. Curr Opin Otolaryngol Head Neck Surg 2006; 14:242–248.
Shindo M. Facial reanimation with microneurovascular free flaps. Facial Plast Surg 2000; 16:357–359.
Birgfeld C, Neligan P. Surgical approaches to facial nerve deficits. Skull Base 2011; 21:177–184.
Sterodimas A, De Faria J, Correa WE, Pitanguy I. Tissue engineering in plastic surgery: an up-to-date review of the current literature. Ann Plast Surg 2009; 62:97–103.
Battiston B, Raimondo S, Tos P, Gaidano V, Audisio C, Scevola A et al.
Tissue engineering of peripheral nerves. Int Rev Neurobiol 2009; 87:227–249.
Siemionow M, Brzezicki G. Current techniques and concepts in peripheral nerve repair. Int Rev Neurobiol 2009; 87:141–172.
Geuna S, Raimondo S, Ronchi G, di Scipio F, Tos P, Czaja K et al.
Histology of the peripheral nerve and changes occurring during nerve regeneration. Int Rev Neurobiol 2009; 87:27–46.
Zhang F, Blain B, Beck J, Zhang J, Chen Z, Chen ZW et al.
Autogenous venous graft with one-stage prepared Schwann cells as a conduit for repair of long segmental nerve defects. J Reconstr Microsurg 2002; 18:295–300.
Strauch B, Rodriguez DM, Diaz J, Yu HL, Kaplan G, Weinstein DE. Autologous Schwann cells drive regeneration through a 6-cm autogenous venous nerve conduit. J Reconstr Microsurg 2001; 17:589–595.
Caplan AI, Dennis JE. Mesenchymal stem cells as trophic mediators. J Cell Biochem 2006; 98:1076–1084.
Tohill M, Terenghi G. Stem‐cell plasticity and therapy for injuries of the peripheral nervous system. Biotechnol Appl Biochem 2004; 40:17–24.
Alhadlaq A, Mao JJ. Mesenchymal stem cells: isolation and therapeutics. Stem Cells Dev 2004; 13:436–448.
Mantovani C, Mahay D, Kingham PJ, Terenghi G, Shawcross SG, Wiberg M. Bone marrow-and adipose-derived stem cells show expression of myelin mRNAs and proteins. Regen Med 2010; 5:403–410.
Cho HH, Jang S, Lee SC, Jeong HS, Park JS, Han JY et al.
Effect of neural‐induced mesenchymal stem cells and platelet‐rich plasma on facial nerve regeneration in an acute nerve injury model. Laryngoscope 2010; 120:907–913.
Meek M, Coert J. Clinical use of nerve conduits in peripheral-nerve repair: review of the literature. J Reconstr Microsurg 2002; 18:97–109.
Terzis JK, Kostas I. Vein grafts used as nerve conduits for obstetrical brachial plexus palsy reconstruction. Plast Reconstr Surg 2007; 120:1930–1941.
Brunelli GA, Battiston B, Vigasio A, Brunelli G, Marocolo D. Bridging nerve defects with combined skeletal muscle and vein conduits. Microsurgery 1993; 14:247–251.
Battiston B, Tos P, Cushway TR, Geuna S. Nerve repair by means of vein filled with muscle grafts I. Clinical results. Microsurgery 2000; 20:32–36.
Ciardelli G, Chiono V. Materials for peripheral nerve regeneration. Macromol Biosci 2006; 6:13–26.
Johnson EO, Soucacos PN. Nerve repair: experimental and clinical evaluation of biodegradable artificial nerve guides. Injury 2008; 39:30–36.
Wang-Bennett LT, Coker NJ. Analysis of axonal regeneration through the silicone regeneration chamber: a retrograde tracing study in the rabbit facial nerve. Exp Neurol 1990; 107:222–229.
Pogrel MA, Mcdonald AR, Kaban LB. Gore-Tex tubing as a conduit for repair of lingual and inferior alveolar nerve continuity defects: a preliminary report. J Oral Maxillofac Surg 1998; 56:319–321.
Chiono V, Tonda‐Turo C, Ciardelli G. Artificial scaffolds for peripheral nerve reconstruction. Int Rev Neurobiol 2009; 87:173–198.
Navissano M, Malan F, Carnino R, Battiston B. Neurotube®
for facial nerve repair. Microsurgery 2005;25:268–271.
Chiono V, Ciardelli G, Vozzi G, Cortez J, Barbani N, Gentile P et al.
Enzymatically‐modified melt‐extruded guides for peripheral nerve repair. Eng Life Sci 2008; 8:226–237.
Kitahara AK, Nishimura Y, Shimizu Y, Endo K. Facial nerve repair accomplished by the interposition of a collagen nerve guide. J Neurosurg 2000; 93:113–120.
Guo BF, Dong MM. Application of neural stem cells in tissue-engineered artificial nerve. Otolaryngol Head Neck Surg 2009; 140:159–164.
Brooks DN, Weber RV, Chao JD, Rinker BD, Zoldos J, Robichaux MR et al.
Processed nerve allografts for peripheral nerve reconstruction: a multicenter study of utilization and outcomes in sensory, mixed, and motor nerve reconstructions. Microsurgery 2012; 32:1–14.
Langhals NB, Urbanchek MG, Ray A, Brenner MJ. Update in facial nerve paralysis: tissue engineering and new technologies. Curr Opin Otolaryngol Head Neck Surg 2014; 22:291–299.