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BACKGROUND: Poly L-lactic acid (PLLA) can stimulate fibrous tissue regeneration to exert a filling effect. However, severe inflammatory reactions and unsatisfactory effects remain a concern. OBJECTIVE: Herein, we describe the mechanism of action, efficacy, and safety of PLLA microspheres in suspension (PLLA-b-PEG/HA) for facial contouring and soft tissue augmentation. METHODS: PLLA-b-PEG/HA, ssynthesized by copolymerization with ethylene glycol, were suspended in hyaluronic acid (HA). Physiological verification was performed using scanning electron microscopy and X-ray computed tomography. PLLA-b-PEG/HA were subcutaneously injected into the dorsal region of 4-month-old rabbits. Ultrasound assessed volumetric capacity at 3 days and 1, 2, 4, and 12 weeks. The inflammatory response, collagen production, and HA degradation were evaluated. A retrospective case series of 10 patients who received PLLA-b-PEG/HA injections was conducted to assess long-term efficacy and safety. RESULTS: PLLA-b-PEG exhibited a spherical structure with a smooth surface (20-45 µm diameter). In rabbits, implant site volume increased within 4 weeks, gradually decreasing thereafter. Fibrous capsules, microvessel density, and new collagen fiber formation progressively increased at 4, 12, and 26 weeks after injection. Clinical data demonstrated significant improvements in face contouring at months 3 and 12 after injection. All patients showed improved internal contours based on the Global Aesthetic Improvement Scale. After 12 months, 90% of the patients retained good shaping and support effects with minimal adverse reactions. CONCLUSIONS: PLLA-b-PEG/HA demonstrated superior biocompatibility and facial regeneration potential, with outstanding dual collagen-stimulating properties. The clinical efficacy and safety of PLLA-b-PEG/HA have been validated and established as a promising therapeutic option.
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Background: When poly-p-dioxanone (PDO) thread is implanted subcutaneously, in addition to collagen hyperplasia, it can also cause denaturation of surrounding adipocytes and reduce the thickness of the fat layer. Hitherto, no studies have thoroughly investigated the effects of PDO thread on adipose tissue. Objectives: In this study, the effect of PDO thread on adipose tissue was investigated in an animal model. Methods: In the current study, PDO thread was implanted into subcutaneous adipose tissue of the back in a miniature pig. Implantation site tissue and control site tissue were taken 12 weeks after implantation for hematoxylin and eosin (H&E) staining and transcriptome sequencing. Gene ontology functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes pathway analysis were performed to investigate the differential gene expression between PDO thread implantation and control site tissue. Results: An obvious decrease in the number, fusion, and denaturation of adipocytes can be seen by H&E staining. Sequencing analysis results showed that many of the genes identified, which were downregulated after PDO thread implantation, were involved in functions and pathways related to lipid metabolism, such as fatty acid metabolism, fatty acid degradation, and lipid cell lipolysis regulation. Some genes related to fatty acid metabolism were significantly downregulated in the PDO tissue at 12 weeks compared to the control tissue. Conclusions: Our results showed PDO thread implantation can cause a decrease in the number of adipocytes, as well as a significant alteration of the expression levels of some genes involved in lipid metabolism-related pathways. PDO thread might play an important role in promoting lipolysis.
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BACKGROUND: Polydioxanone (PDO) threads have been widely used to tighten and lift the facial soft tissue. OBJECTIVE: This research aims to determine the collagenation and inflammation changes that occur in the adipose tissue over time when different types of threads are implanted. METHODS & MATERIALS: Three threads types, PDO, poly glycolic-co-lactic acid (PGLA), and nylon, were inserted in the subcutaneous fat of 12-month-old Bama miniature pigs. Collagen production and inflammatory response were evaluated by hematoxylin and eosin and Masson trichrome staining at 1, 4, 12, 24, and 48 weeks. RESULTS: The integrity of the PDO thread lasted up to 24 weeks with mild inflammation and collagen production. The PGLA thread integrity lasted until 12 weeks and had a strong inflammatory response. The nylon thread's integrity was maintained for 48 weeks and showed minor inflammation and collagen production. CONCLUSION: Our data suggest that PDO thread is the best choice for clinicians, as it has a mild action process with minimal irritation, moderate collagen production, a reasonable explanation time, with obvious bridging fibrous tissue, and thickening action for the superficial fascia.
Subject(s)
Polydioxanone , Rhytidoplasty , Swine , Animals , Nylons , Rhytidoplasty/methods , Collagen , InflammationABSTRACT
Chronic neuropathic pain (CNP) can result from surgery or traumatic injury, but also from peripheral neuropathies caused by diseases, viral infections, or toxic treatments. Opioids, although very effective for acute pain, do not prevent the development of CNP, and are considered as insufficient treatment. Therefore, there is high need for effective and safe non-opioid options to treat, prevent and eventually reverse CNP. A more effective approach to alleviating CNP would constitute a treatment that acts concurrently on various mechanisms involved in relieving pain symptoms and preventing or reversing chronification by enhancing both neuroprotection and neuroregeneration. We have identified and characterized GRT-X (N-[(3-fluorophenyl)-methyl]-1-(2-methoxyethyl)-4-methyl-2-oxo-(7-trifluoromethyl)-1H-quinoline-3-caboxylic acid amide), a novel drug which is able to activate both voltage-gated potassium channels of the Kv7 family and the mitochondrial translocator protein 18 kDa (TSPO). The dual mode-of-action (MoA) of GRT-X was indicated in in vitro studies and in vivo in a rat model of diabetic neuropathy. In this model, mechanical hyperalgesia was dose-dependently inhibited. After severe crush lesion of cervical spinal nerves in rats, GRT-X promoted survival, speeded up regrowth of sensory and motor neurons, and accelerated recovery of behavioral and neuronal responses to heat, cold, mechanical and electrical stimuli. These properties may reduce the likelihood of chronification of acute pain, and even potentially relieve established CNP. The absence of a conditioned place preference in rats suggests lack of abuse potential. In conclusion, GRT-X offers a promising preclinical profile with a novel dual MoA.
Subject(s)
Acute Pain , Neuralgia , Acute Pain/drug therapy , Animals , Hyperalgesia/metabolism , Nerve Regeneration , Neuralgia/metabolism , Neuroprotection , RatsABSTRACT
Objective: To investigate the effectiveness of facial nerve-sublingual nerve parallel bridge anastomosis for facial nerve injury resulting from closed temporal bone fractures. Methods: Between January 2017 and December 2019, 9 patients with facial nerve injury resulting from closed temporal bone fracture caused by head and face trauma were treated. Among them, 5 patients were treated with facial nerve-sublingual nerve parallel bridge anastomosis (operation group), and 4 patients were treated with neurotrophic drugs combined with rehabilitation exercise (conservative group). There was no significant difference in gender, age, side, cause of injury, duration of facial nerve injury before surgery, House-brackmann grading (hereinafter referred to as HB grading) of facial nerve injury, and other general information between 2 groups ( P>0.05). HB grading was used to evaluate the improvement of facial nerve function before and after treatment. At the same time, facial nerve neuroelectrophysiological test was performed to evaluate the electrical activity of facial muscles before and after treatment. Tongue function, atrophy, and tongue deviation were evaluated after nerve anastomosis according to the tongue function scale proposed by Martins et al. Results: Patients in both groups were followed up 12-30 months, with an average of 25 months. None of the 5 patients in the operation group showed symptoms such as tongue muscle atrophy, tongue extension deviation, hypoglossal nerve dysfunction (mainly including slurred speech, choking with water), postoperative infection, bleeding, lower limb muscle atrophy or lower limb motor dysfunction after sural nerve injury. Postoperative skin sensory disturbance in lateral malleolus area was found, but gradually recovered to normal. During the follow-up, facial nerve and sublingual motor neurons were innervated to paralyzed facial muscle in the operation group. At last follow-up, the HB grading of 5 patients in the operation group improved from preoperative grade â ¤ in 2 cases, grade â ¥ in 3 cases to grade â ¡ in 3 cases, grade â ¢ in 1 case, and grade â £ in 1 case. And in the conservative group, there were 1 patient with grade â ¤ and 3 patients with grade â ¥ before operation, facial asymmetry continued during follow-up, and only 2 patients improved from grade â ¥ to grade â ¤ at last follow-up. There was significant difference in prognosis HB grading between the two groups ( t=5.693, P=0.001). In the operation group, the amplitude and frequency of F wave were gradually improved, and obvious action potential could be collected when the facial muscle was vigorously contracted. On the contrary, there was no significant difference in neuroelectrophysiological results before and after treatment in the conservative group. Conclusion: Facial nerve-sublingual nerve parallel bridge anastomosis can effectively retain the integrity of the facial nerve, while introducing the double innervation of the sublingual nerve opposite nerve, which is suitable for the treatment of severe incomplete facial nerve injury caused by closed fracture.
Subject(s)
Facial Nerve Injuries , Facial Paralysis , Fractures, Bone , Anastomosis, Surgical/adverse effects , Anastomosis, Surgical/methods , Facial Nerve/surgery , Facial Nerve Injuries/etiology , Facial Nerve Injuries/surgery , Facial Paralysis/etiology , Facial Paralysis/rehabilitation , Facial Paralysis/surgery , HumansABSTRACT
OBJECTIVE: Functional deficits induced by nerve injuries can be restored by achieving effective reinnervation of the denervated targets and functional reorganization of the central nervous system after nerve reconstruction. In this study, we investigated the effect and extent of cortical functional reorganization related to the ability of transferred hypoglossal neurons to restore facial function in facial paralysis patients after a surgical bridge of neurorrhaphy ectopically between the ipsilateral hypoglossal nerve and injured facial nerve. METHODS: We treated 23 patients (35.4 ± 10.3 years, 10 males) and followed them up for 2.9 ± 0.61 years. We used motor-task-related functional magnetic resonance imaging to map activation change at multiple time points before and after neurorrhaphy; 20 normal subjects were included as control. RESULTS: All patients regained facial function to some extent after neurorrhaphy. Enhanced activation in motor-related cortices gradually returned to normal levels and was positively correlated with regained facial function. The related cortical functional areas included the left middle temporal gyrus, left inferior frontal gyrus, insula, bilateral motor cortex and the supplementary motor area extending to the paracingulate involved in intensive eye closing, as well as the left superior temporal gyrus, right putamen and the bilateral motor cortex involved in lip pursing. Intriguingly, significant correlations were found between the pre-surgery activation while intensive eye closing in bilateral motor cortex and recovery of facial nerve function induced by the neurorrhaphy treatment. CONCLUSION: This is the first study mapping activation change in motor cortices at multiple time points before and after repair of the facial nerve. The cortex functional reorganization found may suggest potential treatment targets in the central nervous system for adjuvant therapies such as repetitive transcranial magnetic stimulation to further improve functional recovery.
Subject(s)
Facial Paralysis , Facial Nerve/surgery , Facial Paralysis/surgery , Humans , Hypoglossal Nerve/surgery , Magnetic Resonance Imaging , Male , Neurosurgical ProceduresABSTRACT
BACKGROUND: Closed temporal bone fractures due to cranial trauma often result in facial nerve injury, frequently inducing incomplete facial paralysis. Conventional hypoglossal-facial nerve end-to-end neurorrhaphy may not be suitable for these injuries because sacrifice of the lesioned facial nerve for neurorrhaphy destroys the remnant axons and/or potential spontaneous innervation. OBJECTIVE: we modified the classical method by hypoglossal-facial nerve "side-to-side" neurorrhaphy using an interpositional predegenerated nerve graft to treat these injuries. METHODS: Five patients who experienced facial paralysis resulting from closed temporal bone fractures due to cranial trauma were treated with the "side-to-side" neurorrhaphy. An additional 4 patients did not receive the neurorrhaphy and served as controls. RESULTS: Before treatment, all patients had suffered House-Brackmann (H-B) grade V or VI facial paralysis for a mean of 5 months. During the 12-30 months of follow-up period, no further detectable deficits were observed, but an improvement in facial nerve function was evidenced over time in the 5 neurorrhaphy-treated patients. At the end of follow-up, the improved facial function reached H-B grade II in 3, grade III in 1 and grade IV in 1 of the 5 patients, consistent with the electrophysiological examinations. In the control group, two patients showed slightly spontaneous innervation with facial function improved from H-B grade VI to V, and the other patients remained unchanged at H-B grade V or VI. CONCLUSIONS: We concluded that the hypoglossal-facial nerve "side-to-side" neurorrhaphy can preserve the injured facial nerve and is suitable for treating significant incomplete facial paralysis resulting from closed temporal bone fractures, providing an evident beneficial effect. Moreover, this treatment may be performed earlier after the onset of facial paralysis in order to reduce the unfavorable changes to the injured facial nerve and atrophy of its target muscles due to long-term denervation and allow axonal regrowth in a rich supportive environment.
Subject(s)
Facial Nerve/physiology , Facial Paralysis/etiology , Facial Paralysis/surgery , Fractures, Bone/complications , Hypoglossal Nerve/physiology , Neurosurgical Procedures/methods , Temporal Bone/injuries , Adolescent , Adult , Female , Follow-Up Studies , Humans , Male , Middle Aged , Neural Conduction , Suture Techniques , Treatment Outcome , Young AdultABSTRACT
OBJECTIVE In this study, the authors used a surgical model of end-to-side neurorrhaphy between a nerve graft and a donor tibial nerve in adult rats to investigate the optimal conditions for axonal regeneration induced by the donor nerve. They also assessed the importance of a more favorable pathway using a predegenerated nerve graft to attract regenerating axons to regrow into the graft and then directing and improving their growth toward the target in comparison with results obtained with a fresh nerve graft. METHODS End-to-side neurorrhaphy was performed between a nerve graft and a donor tibial nerve. The nerve graft was obtained from the left tibial nerve, which was either freshly removed or predegenerated 1 week prior to neurorrhaphy. The donor right tibial nerve was injured by epineurium removal alone, injured by epineurium removal with cross section of 20% or 50% of the total axons at the coaptation site, or left intact. The animals were followed postoperatively for a 6-week period, and outcomes were evaluated by optical microscopy and retrograde labeling to detect the regenerated primary sensory neurons located in the lumbar dorsal root ganglia and spinal motor neurons located in the lumbar spinal ventral horn. RESULTS At the end of the follow-up period, no regenerating axons were observed in the nerve grafts when the donor nerve was left intact, and very few axons were detected when the donor nerve was injured by epineurium removal alone. However, numerous regenerating axons appeared in the grafts when the donor nerve was axotomized, and the greatest number was achieved with a 50% cross section axotomized nerve. In the rats with a 50% cross section of the donor nerve, better nerve-like morphology of the grafts was observed, without connective adhesions. When a predegenerated nerve graft was used, more regenerating axons were attracted and elongated with a more regular shape and improved myelination. CONCLUSIONS Axonal regrowth into a nerve graft depends on axotomy of the donor nerve after end-to-side neurorrhaphy. More efficient attraction and an improved structure of the regenerating axons were achieved when a predegenerated nerve graft was used. Furthermore, a nerve graft may require a certain number of regenerating axons to maintain a nerve-like morphology.
Subject(s)
Axotomy/methods , Nerve Regeneration , Peripheral Nerve Injuries/surgery , Tibial Nerve/injuries , Tibial Nerve/transplantation , Tissue Transplantation/methods , Anastomosis, Surgical/methods , Animals , Disease Models, Animal , Male , Rats , Rats, Sprague-DawleyABSTRACT
BACKGROUND: Facial nerve paralysis in patients occurs in varying degrees of self-image disorders, both physically and mentally, resulting in low self-esteem, anxiety, depression, and even suicide; however, there were few researches on psychological problems in facial palsy patients at home and abroad. This study's objective was to investigate post-traumatic growth (PTG) in facial nerve palsy patients and analyze its influencing factors. METHODS: Using the convenience sampling method, a total of 47 patients with facial nerve paralysis were enrolled in the current study between June 1, 2016, and May 31, 2017. Post-traumatic growth rating scale was utilized to investigate the post-traumatic growth of these patients, and factors influencing patients' post-traumatic growth were analyzed through collecting the general sociological information, disease-related information, simple coping style questionnaire, and social support rating scale. RESULTS: The total score of post-traumatic growth in patients with facial nerve paralysis was mean (M) = 63.1, standard deviation (SD) = 19.14. The ranking of five dimensional scores from high to low was as follows: new possibilities, personal strength enhancement, appreciation of life, mental changes, and improvement of relationships with others. Multiple linear regression analysis showed that six variables, namely, the personality type, duration with facial nerve paralysis, and four coping styles, consisting of three types of positive coping styles and one negative coping style, could explain 71.6% of the total post-traumatic growth score. CONCLUSIONS: Post-traumatic growth in facial nerve palsy patients is moderate. The personality type of patients, the disease duration, and the coping style are the primary influencing factors. Therefore, clinical staffs should perform personalized nursing protocol and psychological intervention for facial nerve palsy patients to reduce their negative mood, improve their compliance with treatment, and help them recover more rapidly.
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TRIAL DESIGN: Hypoglossal-facial nerve (HN-FN) neurorrhaphy is a method commonly used to treat facial palsy when the proximal stump of the injured FN is unavailable. Since the classic HN-FN neurorrhaphy method that needs to section the injured FN is not suitable for incomplete facial palsy, we investigated a modified method that consists of HN-FN 'side'-to-side neurorrhaphy, retaining the remaining or spontaneously regenerated FN axons while preserving hemihypoglossal function. METHODS: To improve axonal regeneration, we used for the first time a predegenerated sural autograft for performing HN-FN 'side'-to-side neurorrhaphy followed by postoperative facial exercise. We treated 12 patients who had experienced FN injury for 1-18â months as a result of acoustic tumour removal. All patients experienced facial grade V-VI paralysis according to the House-Brackmann scale, but their FN was anatomically preserved. No spontaneous facial reinnervation was detected before repair. RESULTS: Although we did not perform fresh nerve grafts and HN-FN 'side'-to-end neurorrhaphy as controls for ethical reasons, the reparative outcomes after nerve reconstruction were remarkable: functional improvements were detected as soon as 3â months after repair, House-Brackmann grade II or III FN functions were achieved in five and four patients, respectively, and there were no apparent signs of synkinesis. The three patients who experienced less satisfactory outcomes had exhibited facial palsy for more than 1â year accompanied by muscle atrophy, consistent with a need for rapid surgical intervention. CONCLUSIONS: Based on fundamental concepts and our experimental results, this new surgical method represents a major advance in the rehabilitation of FN injury. TRIAL REGISTRATION NUMBER: JS2013-001-02.
Subject(s)
Cerebellopontine Angle/surgery , Facial Nerve/surgery , Facial Paralysis/surgery , Hypoglossal Nerve/surgery , Neuroma, Acoustic/surgery , Adult , Aged , Electromyography , Facial Paralysis/etiology , Female , Humans , Male , Middle Aged , Sural Nerve/transplantation , Treatment Outcome , Young AdultABSTRACT
The aim of this study was to determine the effectiveness of hypoglossal-facial nerve "side"-to-end (HemiHN-FN) and accessory-facial nerve end-to-end (AN-FN) neurorrhaphy using a predegenerated nerve graft (PNG) for reanimating facial paralysis in a rat FN injury model. A total of 25 rats with complete unilateral facial paralysis resulting from section of the right FN were divided into 5 groups (n=5 each) that were submitted to immediate, delayed (3 months after FN injury) or no (control) FN reconstruction procedures involving HemiHN-FN or AN-FN neurorrhaphy. Approximately 3 months after FN reconstruction, cholera toxin subunit B conjugate Alexa 555 (CTB-Alexa 555) was injected into the ipsilateral whisker pad muscle and CTB-Alexa 555-labeled neurons were observed in the hypoglossal or accessory nuclei of all the FN reconstruction rats, but none of these neurons were found in the controls. There were numerous myelinated and nonmyelinated axons in both PNG and repaired FN of the FN reconstruction rats. No differences were found for these numbers between the two neurorrhaphy methods for each of the treatment time points, indicating the equal effectiveness of axon regeneration. However, a significantly higher number of CTB-Alexa 555-labeled neurons was observed in the hypoglossal nucleus of the immediate HemiHN-FN neurorrhaphy-treated rats when compared to that in the accessory nucleus of the immediate AN-FN neurorrhaphy-treated rats, consistent with the surface values of the recorded MAPs at the whisker pad muscle while electro-stimulating the FN. These results suggest that HemiHN-FN neurorrhaphy produces more efficient innervation of the paralyzed facial muscles than AN-FN neurorrhaphy without sacrificing ipsilateral hypoglossal function. Taking into consideration the clinical relevance of these findings for postoperative complications and functional reanimation in relation to the central plasticity, we suggest that HemiHN-FN neurorrhaphy may be the preferable facial reanimation procedure after an FN injury.