Platelet-Rich Plasma Lysate Enhances the Osteogenic Differentiation of Adipose-Derived Stem Cells.

ABSTRACT: Adipose-derived stem cells (ADSCs) have become an accepted source of cells in bone tissue engineering. This study aimed to investigate whether platelet-rich plasma (PRP) lysate can replace traditional fetal bovine serum as a culture medium with the enhanced proliferation and osteogenic potential of ADSCs. We divided the experiment into 5 groups where the ADSCs were cultured in an osteogenic medium containing 2.5%, 5%, 7.5%, and 10% PRP lysate with 10% fetal bovine serum as the control group. The cell proliferation, alkaline phosphatase (ALP) activity, ALP stain, alizarin red stain, osteocalcin (OCN) protein expression, and osteogenic-specific gene expression were analyzed and compared among these groups. The outcome showed that all PRP lysate-treated groups had good ALP stain and ALP activity performance. Better alizarin red stains were found in the 2.5%, 5%, and 7.5% PRP lysate groups. The 2.5% and 5% PRP lysate groups showed superior results in OCN quantitative polymerase chain reaction, whereas the 5% and 7.5% PRP lysate groups showed higher OCN protein expressions. Early RUNX2 (Runt-related transcription factor 2 () genes were the most expressed in the 5% PRP lysate group, followed by the 2.5% PRP lysate group, and then the 7.5% PRP lysate group. Thus, we concluded that 5% PRP lysate seemed to provide the optimal effect on enhancing the osteogenic potential of ADSCs. Platelet-rich plasma lysate-treated ADSCs were considered to be a good cell source for application in treating nonunion or bone defects in the future.

Injectable gelatin/glucosamine cryogel microbeads as scaffolds for chondrocyte delivery in cartilage tissue engineering.

In this study, we fabricate squeezable cryogel microbeads as injectable scaffolds for minimum invasive delivery of chondrocytes for cartilage tissue engineering applications. The microbeads with different glucosamine concentrations were prepared by combining the water-in-oil emulsion and cryogelation through crosslinking of gelatin with glutaraldehyde in the presence of glucosamine. The physicochemical characterization results show the successful preparation of cryogel microbeads with uniform shape and size, high porosity, large pore size, high water uptake capacity, and good injectability. In vitro analysis indicates proliferation, migration, and differentiated phenotype of rabbit chondrocytes in the cryogel scaffolds. The seeded chondrocytes in the cryogel scaffold can be delivered by injecting through an 18G needle to fully retain the cell viability. Furthermore, the incorporation of glucosamine in the cryogel promoted the differentiated phenotype of chondrocytes in a dose-dependent manner, from cartilage-specific gene expression and protein production. The in vivo study by injecting the cryogel microbeads into the subcutaneous pockets of nude mice indicates good retention ability as well as good biocompatibility and suitable biodegradability of the cryogel scaffold. Furthermore, the injected chondrocyte/cryogel microbead constructs can form ectopic functional neocartilage tissues following subcutaneous implantation in 21 days, as evidenced by histological and immunohistochemical analysis.

Craniofacial involvement in Langerhans cell histiocytosis: A review of 44 cases at a single medical center.

BACKGROUND: Craniofacial bones are the most commonly involved site of Langerhans cell histiocytosis (LCH). The main purpose of this study was to clarify the relation between subsites of craniofacial bone and clinical presentation, treatment modalities, outcomes, and permanent consequences (PCs) in patients with LCH. METHODS: Forty-four patients diagnosed with LCH involving the craniofacial region presenting at a single medical center during 2001-2019 were collected and divided into four groups: single system with unifocal bone lesion (SS-LCH, UFB); single system with multifocal bone lesions (SS-LCH, MFB); multisystem without risk organ involvement (MS-LCH, RO-); and multisystem with risk organ involvement (MS-LCH, RO+). Data including demographics, clinical presentation, treatments, outcomes, and the development of PC were retrospectively reviewed. RESULTS: Temporal bone (66.7% versus 7.7%, p = 0.001), occipital bone (44.4% versus 7.7%, p = 0.022), and sphenoid bone (33.3% versus 3.8%, p = 0.041) involvement were more common in SS-LCH, MFB than they were in SS-LCH, UFB. No difference of reactivation rate was noted among the four groups. The most common PC is diabetes insipidus (DI), reported in 9 of the 16 (56.25%) patients with PC. The single system group was reported with the lowest incidence of DI (7.7%, p = 0.035). The reactivation rate was also higher in patients with PC (33.3% versus 4.0%, p = 0.021) or DI (62.5% versus 3.1%, p < 0.001). CONCLUSION: An increased risk of multifocal or multisystem lesions was associated with temporal bone, occipital bone, sphenoid bone, maxillary bone, eye, ear, and oral involvement, which may indicate poor outcomes. Longer follow-up may be indicated if there is the presence of PC or DI due to the high risk of reactivation. Therefore, multidisciplinary evaluation and treatment according to risk stratification are vital for patients diagnosed with LCH involving the craniofacial region.

The Comparison of Functional Outcomes in Patients With Unilateral or Bilateral Intracapsular Mandibular Condylar Fractures After Closed or Open Treatment: A 10-Year Retrospective Study.

BACKGROUND: The treatment strategies for mandibular condylar head fractures, also known as intracapsular condylar fractures (ICFs), have not been concluded. We humbly present our treatment outcomes and share our experience in our department. AIMS AND OBJECTIVES: The aim of this study was to compare the functional outcomes between closed reduction (CR) and open reduction and internal fixation (ORIF) for management of unilateral or bilateral ICFs. MATERIALS AND METHODS: This 10-year retrospective cohort study included 71 patients with 102 ICFs who were treated in our department from May 2007 to August 2017. Nine patients mixed with extracapsular fractures were excluded; thus, 62 patients with 93 ICFs were included. All patients received treatment by the senior surgeon in Chang Gung Memorial Hospital, Linkou Branch, Taiwan. The patient's basic data, fracture morphologies, associated injuries, managements, complications, and maximal mouth opening (MMO) measurement at 1, 3, 6, and 12 months postoperative were reviewed for analysis. RESULTS: Among the 93 fractures, 31 (50%) were bilateral and 31 were unilateral (50%). Based on He's classification, 45 (48%) had type A fracture, 13 (14%) had type B, 5 (5%) had type C, 20 (22%) had type M, and 10 (11%) had no displacement. Maximal mouth opening of 37 mm in unilateral cases after 6 months was significantly higher than the 33-mm MMO in bilateral cases. In addition, the MMO in the ORIF group was significantly higher than that of the CR group in 3 months postoperative. Univariate (odds ratio, 4.92; P = 0.01) and multivariate (odds ratio, 4.76; P = 0.027) analyses revealed CR as an independent risk factor for trismus development compared with ORIF. Malocclusion was observed in 5 patients in both CR and ORIF groups. In addition, 1 patient developed temporomandibular joint osteoarthritis in the CR group. No surgical-related temporary or permanent facial nerve palsy was observed. CONCLUSIONS: Open reduction and internal fixation for condylar head fracture provided better recovery in MMO than CR, and the MMO recovery was less in bilateral condylar head fracture than unilateral condylar head fracture. Open reduction and internal fixation in ICFs have a lower risk for trismus development and should be the treatment of choice in selected cases.

Facial Fracture Patterns and Severity of Associated Injuries After Motorcycle Accidents.

BACKGROUND: Motorcycle injuries remain a significant cause of motor vehicle-related morbidity and mortality in Taiwan. Besides, the facial region is a commonly fractured site under motorcycle accidents. To date, there are no trauma mechanism-based studies of facial fractures. AIM AND OBJECTIVES: This study aims to determine the facial fracture patterns, the severity of head trauma, and associated injuries by different motorcycle-related trauma mechanisms enabling a greater understanding of its distribution and magnitude. METHODS: This is a retrospective descriptive analysis conducted over a 2-year period at Linkou Chang Gung Memorial Hospital. We focused on the population of maxillofacial injury caused by motorcycle accidents. We divided the patient cohort into 3 main trauma mechanisms: single-motorcycle collision (SM group), motorcycle-to-motorcycle collision (MM group), motorcycle-to-vehicle collision (MV group). Data, including demographics, age, fracture patterns of facial bones, and other associated injuries, were collected. RESULTS: A total of 881 cases were identified that involved facial fractures. Most patients were male (71%), young adult (mean age, 32.49 years), and the most common fracture region is the midfacial fracture (79.5%, 700 victims). Among the 3 groups, the MM group was less likely to sustain severe injuries by trauma score system, less head injury and mortality rate. The MV group and SM group have similar mortality rates but different fracture pattern tendencies. Lower facial fractures were more likely in the MV group, but midface fractures in the SM group. Associated injuries were higher in the MV group. CONCLUSIONS: Our study presents the different trends of fracture patterns and injury under 3 main mechanisms of motorcycle casualties. We document all these data in the hope of providing insights into trauma doctors dealing with motorcycle accidents.

Comparison of the Effectiveness Between Conventional and Modified Cinch Suture Techniques in LeFort I Osteotomy: A Systematic Review and Meta-Analysis of Randomized Control Trials.

BACKGROUND: LeFort I osteotomy changes the morphology of the nose. The cinch suture has been proven to prevent the increase in nasal base and alar width. Different types of cinch sutures have been proposed. However, their effectiveness is unclear. AIM AND OBJECTIVES: The aim of this study was to compare the surgical outcomes between conventional and modified cinch techniques through a systematic review and meta-analysis of randomized control trials (RCTs). MATERIAL AND METHODS: We performed systematic search from Embase, PubMed, and the Cochrane Library according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement up to March 2021. The surgical techniques of different cinch sutures were reviewed, and the outcomes of nasal alar width and alar base width were compared between modified and conventional methods. RESULTS: A total of 4 eligible RCTs were included in this meta-analysis. Pooled data showed no significant difference in alar base width change between modified and conventional methods (mean difference, -0.37; 95% confidence interval, -1.32 to 0.57; P = 0.44). Pooled data of 3 studies also showed no significant difference in nasal alar width change (mean difference, -0.11; 95% confidence interval, -1.18 to 0.95; P = 0.83). CONCLUSION: Based on the current data pooled from the available RCTs, no significant difference was found between the conventional cinch technique and the modified technique.

Application of Orthognathic Surgery Principles and Techniques in the Management of Craniomaxillofacial Trauma.

BACKGROUND: Posttraumatic secondary deformities of facial skeleton may occur because of nonmanagement or ill management of primary injuries, whereas some unexpectedly occur even after dedicated management attempts. Orthognathic surgery (OGS) principles and techniques can be used as an efficient tool to correct posttraumatic craniomaxillofacial deformities or skeletal developmental deformities during trauma management. AIM AND OBJECTIVES: The aims of this study were to describe the different types of posttraumatic secondary deformity and address how to use the principles of orthognathic techniques to correct them. MATERIALS AND METHODS: Patients with orthognathic surgical osteotomies during primary or secondary management of facial trauma (referred to as trauma-OGS) during the period of 2010 to 2018 were retrospectively reviewed. Variables pertaining to patients and surgery were collected, including trauma diagnosis, etiology, duration between trauma/primary surgery and secondary presentation, suggested reason for secondary deformity, intervention undertaken to address, and the surgical outcome. RESULTS: Twenty-seven patients were eligible and extensively reviewed. Etiological categorization of trauma-OGS could be done into posttraumatic deformities (18) and developmental deformities (9). The former group was further categorized as OGS done as primary procedure (8) that included immobile Le Fort fractures and delayed initial treatment, and OGS done as secondary procedure (10) that included complex fractures and condylar fractures. The developmental deformity group was categorized into OGS done simultaneously during trauma management (5) or done as a secondary procedure after trauma management (4). CONCLUSIONS: Application of principles and techniques of OGS in indicated primary or secondary management of facial trauma patients should always be considered. The categorization of scenarios presented in this article relating facial trauma and OGS may further help to understand the application.

Aesthetic Outcome of Primary Rhinoplasty of Saddle Nose Deformity in Naso-Orbital Ethmoidal Fractures in Asian Patients.

BACKGROUND: Saddle nose deformity following naso-orbital ethmoidal (NOE) fractures remain a challenging problem for the reconstructive surgeon. Early reduction and internal fixation allow for fracture stabilization but is unable to address the problem of the depressed nasal dorsum, especially after soft tissue shrinkage. The aim of this study is to evaluate the outcome of primary rhinoplasty in patients with NOE fractures. MATERIALS AND METHODS: From 2016 to 2019, 9 patients presented to our department with NOE fractures complicated by saddle nose deformity underwent primary nasal reconstruction at the time of their fracture fixation. Life size (1:1) frontal and lateral postoperative photographs were taken. Three objective measurements were made, including the nasofrontal angle, tip projection, and radix projection. These measurements were compared between normal persons (group 1), preoperative patients (group 2), and postoperative patients (group 3). Nose aesthetic assessment was carried out via a panel assessment using a Visual Analog Scale of 5. Patient satisfaction was further assessed subjectively by the patient themselves using the Visual Analog Scale. RESULTS: When comparing group 3 to 2, a significant reduction in the nasofrontal angles was found with an accompanying increase in the radix and tip projection ( P <0.05). No statistical significance between normal persons and postprimary rhinoplasty patients was noted between groups 1 and 3. Average patient satisfaction scored 3.86±1.07 compared with 3.63±0.84 by laypersons and 4±0.77 by specialists' panel. CONCLUSION: Primary nasal reconstruction may be an alternative method for achieving optimum results following NOE fractures preventing the development of secondary saddle nose deformity with a shortened nose which may potentially be more difficult to correct.

Preliminary outcomes of the surgical navigation system combined with intraoperative three-dimensional C-arm computed tomography for zygomatico-orbital fracture reconstruction.

This study analyzed the outcomes of zygomatico-orbital fracture reconstruction using the real-time navigation system with intraoperative three-dimensional (3D) C-arm computed tomography (CT). Fifteen patients with zygomatico-orbital or isolated orbital/zygoma fractures were enrolled in this prospective cohort. For zygoma reduction, the displacement at five key sutures and the differences between preoperative and intraoperative CT images were compared. For orbital reconstruction, the bilateral orbital volume differences in the anterior, middle, and posterior angles over the medial transitional buttress were measured. Two patients required implant adjustment once after the intraoperative 3D C-arm assessment. On comparing the preoperative and postoperative findings for the zygoma, the average sum of displacement was 19.48 (range, 5.1-34.65) vs. 1.96 (0-3.95) mm (P < 0.001) and the deviation index was 13.56 (10-24.35) vs. 2.44 (0.6-4.85) (P < 0.001). For the orbit, the mean preoperative to postoperative bilateral orbital volume difference was 3.93 (0.35-10.95) vs. 1.05 (0.12-3.61) mm3 (P < 0.001). The mean difference in the bilateral angles at the transition buttress was significantly decreased postoperatively at the middle and posterior one-third. There was no significant difference in orbital volume, angle of the transition zone, and the sum of five zygoma distances between post operative results and preoperative virtual planning. The surgical navigation system with the intraoperative 3D C-arm can effectively improve the accuracy of zygomatico-orbital fracture reconstruction and decrease implant adjustment times.

Outcome Analysis of Surgical Timing in Pediatric Orbital Trapdoor Fracture with Different Entrapment Contents: A Retrospective Study.

Orbital trapdoor fracture occurs more commonly in pediatric patients, and previous studies suggested early intervention for a better outcome. However, there is no consensus on the appropriate timing of emergent intervention due to the insufficient cases reported. In the current retrospective study, we compared the outcomes of patient groups with different time intervals from injury to surgical intervention and entrapment content. Twenty-three patients who underwent surgery for trapdoor fracture between January 2001 and September 2018 at Chang Gung Memorial Hospital were enrolled. There was no significant difference in diplopia and extraocular muscle (EOM) movement recovery rate in patients who underwent surgery within three days and those over three days. However, among the patients with an interval to surgery of over three days, those with muscle entrapment required a longer period of time to recover from EOM movement restriction (p = 0.03) and diplopia (p = 0.03) than those with soft tissue entrapment. Regardless of time interval to surgery, patients with muscle entrapment took longer time to recover from EOM movement restriction (p = 0.036) and diplopia (p = 0.042) and had the trend of a worse EOM recovery rate compared to patients with soft tissue entrapment. Hence, we suggested that orbital trapdoor fractures with rectus muscle entrapment should be promptly managed for faster recovery.

Application of real-time surgical navigation for zygomatic fracture reduction and fixation.

BACKGROUND: Inappropriate treatment of zygomatic fractures can reduce esthetic and functional outcomes. The aim of this study was to answer the research question: "Among patients with a unilateral zygomatic fracture, is the use of computer-assisted real-time navigation system during fracture reduction precise and accurate to create postoperative facial symmetry?" METHODS: Using a retrospective cohort study design, we enrolled a cohort of unilateral zygomatic fractures undergoing open reduction and internal fixation (ORIF) with the aid of the computer-based navigation system at Chang Gung Memorial Hospital, Taiwan, during January 2015 and March 2018. The predictor variable was the comparison before and after surgery. The main outcome variables included (1) two-dimensional (2D) reduction of the displacement at five anatomical landmarks: zygomaticofrontal, inferior orbital rim, zygomaticosphenoidal, zygomaticomaxillary, and zygomaticotemporal lines/buttresses and (2) three-dimensional (3D) differences on distances between zygomatic surface to the porion plane and the midpoint of zygomatic arch (ZA) to the mid-porion (MP) plane. The Wilcoxon signed-rank test was computed to compare between pre- and postoperative data, and a p-value less than 0.05 was considered statistically significant. RESULTS: The cohort comprised 24 subjects (50% females, 75% left-sided) with a mean age of 30.5 +/- 13.8 years. On 2D analysis, the significant fracture reduction was found: 4.78 vs. 1.22 mm, 1.78 vs. 0.40 mm, 3.50 vs. 0.07 mm, 3.06 vs. 0.55 mm, and 2.55 vs. 0.50 mm at zygomaticomaxillary, zygomaticofrontal, inferior orbital rim, zygomaticosphenoidal, and zygomaticotemporal landmarks. The 3D evaluations revealed the significant reduction of the differences between the left and right zygomatic surface to the porion plane (4.09 ± 2.12 vs. 0.46 ± 0.35 mm) and between the left and right ZA midpoints to the MP plane (4.89 ± 2.59 vs. 0.71 ± 0.44 mm) (p<0.001 for both 2D and 3D analyses). CONCLUSIONS: The results of this study suggest that the real-time surgical navigation system can effectively guide the ORIF of zygomatic fractures. Future research studies should focus on the learning curve and cost-effectiveness analysis of this technique.

Lower Eyelid and Midface Rejuvenation: Suborbicularis Oculi Fat Lift.

The lower eyelids and midface are considered to be a contiguous aesthetic unit although they are different anatomic structures. Through in-depth understanding of complex anatomy and aging theory and appropriate surgical strategies according to the type of aging, surgical outcome of aging lower eyelid/midface can be more and more predictable. This article discusses the characteristics and theories of aging and 5 types of lower eyelid/middle face aging based on 4 key factors, namely, protruding fat in the orbital, excess skin on the lower eyelid, sagging midface and soft tissue deflation. Various combinations of surgical strategies are adopted accordingly.

Early escharotomy-like procedure for the prevention of extremity autoamputation in harlequin ichthyosis.

Harlequin ichthyosis is a rare congenital disorder, which causes restrictive circumferential encasement of the trunk and limbs. Patients usually develop compartment syndrome and sequential cyanosis of limbs and digits, leading to autoamputation. We report a case of harlequin ichthyosis in which all digits were preserved with an early escharotomy-like procedure. A 33-6/7-week-old preterm girl presented with whole body hyperkeratosis, constrictive bands on neck, chest, abdominal, limbs, and developed compartment syndrome. On the second day after birth, distal digits progressive swelling and ischemic change occurred. An escharotomy-like procedure was performed on all 4 extremities to the distal digits. All distal phalanges and nail plate were well preserved at 5-month follow-up. We concluded that for prevention of digits autoamputation in harlequin ichthyosis, early detection of compartment syndrome is necessary and an escharotomy-like procedure should be performed as soon as possible when ischemia occurs.

A bioactive multi-functional heparin-grafted aligned poly(lactide-co-glycolide)/curcumin nanofiber membrane to accelerate diabetic wound healing.

Curcumin is reported to possess excellent efficacy to treat wounds that exhibit impaired healing. Heparin shows high affinity for many growth factors that are key biological mediators during the wound healing process. In this study, we aimed to prepare wound dressing membranes, for sustained release of an exogenous factor curcumin as well as sequestering endogenous growth factors at the wound site, to promote wound healing in diabetic rats. Toward this end, we prepared aligned curcumin-loaded poly(lactide-co-glycolide) (PLGA) nanofiber membranes (PC NFMs), followed by high density surface grafting of heparin to fabricate PLGA/curcumin (PCH) NFMs. Both PC and PCH NFMs show high tensile strength, low cytotoxicity and suitable water vapor transmission rate for application as wound dressings. Nonetheless, the PCH NFM shows higher curcumin release rate than PC due to enhanced hydrophilicity, which leads to higher cell migration rate and induced oxidative stress protection of HS68 fibroblast cells in vitro. In vivo study indicated the PCH exhibits the fastest wound closure rate among all membranes with accelerated re-epithelization rate, higher angiogenesis rate and more collagen deposition at the wound site. The accelerated and better skin tissue regeneration could be suggested to correlate with the multi-functionality of nanofibers, where grafted heparin attracting and stabilizing the growth factors important for wound healing in situ, together with relieving the high oxidative stress and the inflammatory cascade from released curcumin during diabetic wound healing.

Le Fort Fractures With Maxillary Immobility: Classification and the Moment Concept to Rationalize Optimal Surgical Treatment.

BACKGROUND: Le Fort fractures with maxillary immobility are an uncommon presentation of facial trauma often associated with the disturbance of occlusion. Historically, cases involving high Le Fort fractures require a coronal extensive approach to mobilize the maxilla for occlusion restoration. Here, we review our institutional series of immobile Le Fort fractures and present their treatment approach, outcomes, classification, and then rationalize our treatment with a concept philosophy. MATERIALS AND METHODS: We treated 12 consecutive patients with unilateral and bilateral immobile Le Fort fractures from 2010 to 2017. The mean age was 27.1 years. Ten patients had a unilateral greenstick Le Fort III fracture. Five patients also had associated mandible fractures. Intraoperative occlusions could only be restored after Le Fort I osteotomy was performed on the side of the immobile Le Fort fracture. The mean follow-up period was 1.6 years. RESULTS: All patients presented good long-term occlusion restoration. There were no cases of nonunion or significant complications. None of the patients complained of any malar or periorbital cosmetic issues during follow-up sessions. CONCLUSIONS: We presented an institutional series and classification of unusual Le Fort fractures with maxillary immobility, including a previously unreported fracture configuration of greenstick unilateral Le Fort III fractures combined with complete contralateral Le Fort I fracture. Based on our moment concept to rationalize treatment, as well as a systematic review of published literature, we advocate the judicious use of Le Fort I osteotomy to efficiently and safely treat these unusual fractures.

Ipsilateral transnasal medial canthopexy to correct secondary telecanthus after naso-orbito-ethmoid fracture.

BACKGROUND: Telecanthus results from medial canthal tendon (MCT) disruption, which can result from traumatic naso-orbito-ethmoid (NOE) fractures. Several methods, using different anchoring materials, incision approaches, or fixation positions, have been proposed for MCT reconstruction. Herein, we report our experience in treating MCT disruption using ipsilateral transnasal medial canthopexy with a Y-V approach. PATIENTS AND METHODS: Between 2008 and 2017, seven patients with traumatic NOE fractures underwent ipsilateral transnasal MCT fixation with Y-V epicanthoplasty. The length ratio, defined as the length of the affected side divided by that of the normal side, was calculated preoperatively and postoperatively. A modified Y-V epicanthoplasty incision was made, after first marking the site in the apex of the caruncular fornix. The nasal wall was exposed and the MCT was accessed carefully. Bulky MCT tissue was trimmed. The lacrimal bone was ground using a bur, creating a concave shape to reposition the MCT, and two holes were drilled into the ipsilateral lacrimal fossa and frontomaxillary process. The MCT was fixed to the frontomaxillary process using no. 2 transnasal wire, which was secured by a 6-mm screw. Finally, the Y-V epicanthoplasty was repaired using 5.0 nylon. RESULTS: The preoperative length ratio (mean±standard deviation: 83.3%±6.0%; range: 73.7%-92.0%) was significantly lower than the postoperative length ratio (mean±standard deviation: 99.4%±0.6%; range: 98.5%-100%) (p<0.05). No major complications were observed, with an average of 13 months of follow-up. CONCLUSIONS: Ipsilateral transnasal wiring fixation with Y-V epicanthoplasty is a useful and adequate method for MCT reconstruction after NOE fractures, without remarkable complications.

Long-gap peripheral nerve repair through sustained release of a neurotrophic factor in nonhuman primates.

Severe injuries to peripheral nerves are challenging to repair. Standard-of-care treatment for nerve gaps >2 to 3 centimeters is autografting; however, autografting can result in neuroma formation, loss of sensory function at the donor site, and increased operative time. To address the need for a synthetic nerve conduit to treat large nerve gaps, we investigated a biodegradable poly(caprolactone) (PCL) conduit with embedded double-walled polymeric microspheres encapsulating glial cell line-derived neurotrophic factor (GDNF) capable of providing a sustained release of GDNF for >50 days in a 5-centimeter nerve defect in a rhesus macaque model. The GDNF-eluting conduit (PCL/GDNF) was compared to a median nerve autograft and a PCL conduit containing empty microspheres (PCL/Empty). Functional testing demonstrated similar functional recovery between the PCL/GDNF-treated group (75.64 ± 10.28%) and the autograft-treated group (77.49 ± 19.28%); both groups were statistically improved compared to PCL/Empty-treated group (44.95 ± 26.94%). Nerve conduction velocity 1 year after surgery was increased in the PCL/GDNF-treated macaques (31.41 ± 15.34 meters/second) compared to autograft (25.45 ± 3.96 meters/second) and PCL/Empty (12.60 ± 3.89 meters/second) treatment. Histological analyses included assessment of Schwann cell presence, myelination of axons, nerve fiber density, and g-ratio. PCL/GDNF group exhibited a statistically greater average area occupied by individual Schwann cells at the distal nerve (11.60 ± 33.01 µm2) compared to autograft (4.62 ± 3.99 µm2) and PCL/Empty (4.52 ± 5.16 µm2) treatment groups. This study demonstrates the efficacious bridging of a long peripheral nerve gap in a nonhuman primate model using an acellular, biodegradable nerve conduit.

Preparation and Characterization of Surface Heat Sintered Nanohydroxyapatite and Nanowhitlockite Embedded Poly (Lactic-co-glycolic Acid) Microsphere Bone Graft Scaffolds: In Vitro and in Vivo Studies.

In the context of using bone graft materials to restore and improve the function of damaged bone tissues, macroporous biodegradable composite bone graft scaffolds have osteoinductive properties that allow them to provide a suitable environment for bone regeneration. Hydroxyapatite (HAP) and whitlockite (WLKT) are the two major components of hard tissues such as bone and teeth. Because of their biocompatibility and osteoinductivity, we synthesized HAP (nHAP) and WLKT nanoparticles (nWLKT) by using the chemical precipitation method. The nanoparticles were separately incorporated within poly (lactic-co-glycolic acid) (PLGA) microspheres. Following this, the composite microspheres were converted to macroporous bone grafts with sufficient mechanical strength in pin or screw shape through surface sintering. We characterized physico-chemical and mechanical properties of the nanoparticles and composites. The biocompatibility of the grafts was further tested through in vitro cell adhesion and proliferation studies using rabbit bone marrow stem cells. The ability to promote osteogenic differentiation was tested through alkaline phosphate activity and immunofluorescence staining of bone marker proteins. For in vivo study, the bone pins were implanted in tibia bone defects in rabbits to compare the bone regeneration ability though H&E, Masson's trichrome and immunohistochemical staining. The results revealed similar physico-chemical characteristics and cellular response of PLGA/nHAP and PLGA/nWLKT scaffolds but the latter is associated with higher osteogenic potential towards BMSCs, pointing out the possibility to use this ceramic nanoparticle to prepare a sintered composite microsphere scaffold for potential bone grafts and tissue engineered implants.

Functional Outcomes of Surgical Management of Mandibular Condylar Head Fractures.

BACKGROUND: Various procedures have been described for the management of mandibular condylar head fracture, but a standard treatment is not yet conclusive. This report describes our experience with osteosynthesis of condylar head fracture at Linkou Chang Gung Memorial Hospital. METHODS: Sixteen patients with unilateral or bilateral mandibular condylar head fractures diagnosed by computed tomography and treated by open reduction and internal fixation between August 2014 and September 2016 were retrospectively reviewed. A preauricular approach was consistently used for internal fixation with 2 microplates and 4 screws after anatomic reduction. Occlusion, maximum mouth opening (MMO), radiographic outcome, and complications were recorded. RESULTS: Mean ± SD patient age was 29.5 ± 11.4 years, and mean ± SD procedure time was 264.3 ± 83.1 minutes. Mean ± SD postoperative MMO was 23.5 ± 10.2 mm at 1 month, 34.1 ± 8.6 mm at 3 months, 39.1 ± 5.7 mm at 6 months, and 40.0 ± 6.8 at 1 year. Early recovery of MMO of greater than 30 mm was achieved by 13 patients at 3 months after open reduction and internal fixation. There were no major complications. CONCLUSIONS: Microplate fixation from the posterior aspect of the mandibular condylar head via the preauricular approach was safe for patients with mandibular condylar head fractures.

Simultaneous Surgical Correction of Skeletal Class III Dentofacial Deformity During Acute Management of Facial Fractures: Patient Selection and Surgical Technique.

BACKGROUND: Mandibular prognathism is a common dentofacial deformity in Asia. Treatment of such condition may vary from orthodontic camouflage to surgical orthodontics with orthognathic surgery depending on the severity of the condition. Because of the prominent position of the mandible, fractures involving different locations of the mandible commonly occur in maxillofacial trauma. Anatomical reduction of maxillofacial fractures and restoration of the pretraumatic occlusion are the primary goals of acute management of facial fractures. In patients with dentofacial deformity, simultaneous surgical correction of their malocclusion and improvement of their facial aesthetics while providing open treatment to the maxillofacial fractures are rarely reported in the literature. PATIENTS AND METHODS: We reported 3 cases with combined open reduction and internal fixation and surgery-first orthognathic surgery principles to correct class III malocclusion with mandibular prognathism during acute management of maxillofacial fractures. Computer-assisted surgical simulation was used in surgical planning and fabrication of surgical splint. RESULTS: Two patients underwent mandibular osteotomies in addition to open reduction and internal fixation of maxillofacial fractures. One patient had both maxillary and mandibular osteotomies during facial fracture repair. Class I occlusion with satisfactory facial profile was achieved in all 3 cases. CONCLUSIONS: Careful patient selection with presurgical planning using computer-assisted surgical simulation is essential in achieving successful outcomes in correcting dentofacial deformities while managing maxillofacial fractures. This combined technique is a viable option in the surgical management of facial fractures in patients with dentofacial deformities.