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This systematic review aims to critically appraise the intraoperative use of augmented and mixed reality technology to improve surgical outcomes.A literature search of PubMed, Scopus, Cochrane Central Register of Controlled Trials, ClinicalTrials.gov and WHO ICTRP was performed in accordance with Cochrane Handbook for Systematic Reviews of Interventions.This review included 94 studies on 2473 patients, comprising 78 studies on augmented reality and 16 on mixed reality. This technology has seen broad intraoperative application. Augmented and mixed reality can reduce operative duration, blood loss, and the duration of inpatient care. Current evidence shows that they achieve this most in percutaneous surgery.Augmented and mixed reality technology improve surgical outcomes by increasing navigational speed and reducing navigational error intraoperatively. However, they have technical limitations which are the subject of ongoing research. Further studies are necessary to define how this technology is best applied intraoperatively.PROSPERO CRD42020205892.

Early diagnosis of wound infections are crucial as they have been shown to increase patient morbidity and mortality. We evaluated the use of Moleculight i:X to identify infections in acute open wounds in hand trauma. Data were collected from patients who attended the hand trauma unit over a 4 week period prior to having surgery. Wounds were inspected for clinical signs of infection and autofluorescence images were taken using the Moleculight i:X device. Wound swabs were taken and results interpreted according to report by microbiologist. Autofluorescence images were interpreted by a clinician blinded to the microbiology results. 31 patients were included and data collected from 35 wounds. 3 wounds (8.6%) showed positive clinical signs of infection, 3 (8.6%) were positive on autofluorescence imaging and 2 (5.7%) of wound swab samples were positive for significant infection. Autofluorescence imaging correlated with clinical signs and wound swab results for 34 wounds (97.1%). In one case, the clinical assessment and autofluorescence imaging showed positive signs of infection but the wound swabs were negative. Autofluorescence imaging in acute open wounds may be useful to provide real-time confirmation of bacterial infection and therefore guide management.

Background The vulva is composed of aesthetic units that can be affected differently by vulvar conditions. A reliable, comprehensive, and quick-to-use clinical scoring system is required to assess the disease extent in the vulvar area. Objectives The aim of this study was to develop and validate a grading scale based on the aesthetic unit principle to evaluate the extent of vulvar lichen sclerosus (VLS). Methods After reviewing photographs of 100 patients affected by VLS, the authors targeted the aesthetic units most frequently affected. The disease signs were recorded and graded in 4 levels of severity (none, mild, moderate, severe) taking into account the vulvar architecture and skin involvement. To validate the scale, 14 observers were asked to apply it to photographs of 25 VLS patients on 2 different occasions. Intra- and inter-observer reliabilities were determined employing Pearson’s and intraclass correlation coefficients. Results A 6-region, 4-point grading system was designed and identified as the Vulvar Architecture Severity Scale (VASS). In all 6 areas, the Pearson’s r was greater than 0.9 (mean, 0.994; 95% confidence interval [CI] = 0.992), indicating that the intra-observer reliability of the VASS was consistent over time (P < 0.001). Intraclass correlation at time 1 was 0.928 (95% CI = 0.910, 0.943) and at time 2 was 0.944 (95% CI = 0.931, 0.996), indicating a high reliability level among different observers. Conclusions The VASS is a reliable scale to assess the severity of VLS, and it might be considered as an outcome measure in future VLS trials. Level of Evidence: 4

Surgical fixation of Bennett’s fracture of the thumb is critical to prevent functional impairment; however, there is no consensus on the optimal fixation method. We performed an 11-year retrospective cohort analysis and a systematic literature review to determine long-term patient-reported outcomes following Bennett’s fracture fixation. Retrospective cohort analysis identified 49 patients treated with Kirschner (K)-wire fixation, 85% returned to unrestricted movement during hand therapy. Forty-seven patients (96%) completed the disabilities of the arm, shoulder, and hand (DASH) questionnaires at a mean of 5.55 years from injury, with a mean score of 7.75. Systematic literature review identified 14 studies with a cumulative 541 patients. Fixation included open or percutaneous methods utilizing K-wires, tension band wiring, lag screws, T-Plates, external fixation, and arthroscopic screw fixation. Functional outcomes reported included DASH, quickDASH (qDASH), and visual analogue scores. Superficial wound infection occurred in 4 to 8% of percutaneous K-wire fixation. Open reduction internal fixation (ORIF) methods were associated with a 4 to 20% rate of reintervention and 5 to 28% rate of persistent paresthesia. Closed reduction with percutaneous K-wire fixation should be the first choice surgical method, given excellent, long-term functional outcomes, and low risk of complications. ORIF should be utilized where closed reduction is not achievable; however, the current evidence does not support one method of ORIF above another.

OBJECTIVE The aim of the study was to evaluate the effect of lipotransfer in women presenting with fibrosis and scarring due to lichen sclerosus. MATERIALS AND METHODS This prospective cohort study included 33 women attending the vulvar clinic of a public hospital. Patients received one lipotransfer treatment. Validated measures were used prospectively to assess the sexual function (Female Sexual Function Index, Female Sexual Distress Scale); symptoms (visual analog scale for itching, burning, soreness), pain (Pain Anxiety Symptoms Scale 20); psychological status and quality of life (Hospital Anxiety and Depression Scale, Relationship Assessment Scale, Wound Management Questionnaire Revised); physician-based disease signs (Vulvar Architecture Severity Scale). Data were analyzed using paired t test with nonparametric Wilcoxon matched-pairs signed rank test and unpaired t test with nonparametric Mann-Whitney test (Prism6 Software). RESULTS The mean (SD) follow-up was 12.9 (3.5) months. Sexual function improved after treatment (p < .001), as well as the distress associated with sexuality (p < .0001). A significant improvement was reported in itching (p < .001), burning (p < .05), soreness (p < .001), and pain (p < .0001). Patients reported a significant improvement in romantic relationship (p < .05), anxiety (p < .0001), and depression (p < .0001). Improvement was not significant in the self-care associated with self-disgust assessment (p = .42). The clinical physician-based score showed an overall improvement in all the treated areas to lesser or greater extent. CONCLUSIONS The use of fat grafting in lichen sclerosus is promising. Further studies are required to rule out a potential placebo effect and to better understand the underlying molecular mechanism of action.

Current surgical reconstruction for soft tissue replacement involves lipotransfer to restore soft tissue replacements but is limited by survival and longevity of the fat tissue. Alternative approaches to overcome these limitations include using biodegradable scaffolds with stem cells with growth factors to generate soft tissue. Adipose derived stem cells (ADSCs) offer great potential to differentiate into adipose, and can be delivered using biodegradable scaffolds. However, the optimal scaffold to maximise this approach is unknown. This study investigates the biocompatibility of nanocomposite scaffolds (POSS-PCL) to deliver ADSCs with and without the addition of growth factors using platelet rich plasma (PRP) in vivo. Rat ADSCs were isolated and then seeded on biodegradable scaffolds (POSS-PCL). In addition, donor rats were used to isolate PRP to modify the scaffolds. The implants were then subcutaneously implanted for 3-months to assess the effect of PRP and ADSC on POSS-PCL scaffolds biocompatibility. Histology after explanation was examined to assess tissue integration (H&E) and collagen production (Massons Trichome). Immunohistochemistry was used to assess angiogenesis (CD3, α-SMA), immune response (CD45, CD68) and adipose formation (PPAR-γ). At 3-months PRP-ADSC-POSS-PCL scaffolds demonstrated significantly increased tissue integration and angiogenesis compared to PRP, ADSC and unmodified scaffolds (p

Introduction Non-surgical / minimally invasive aesthetic procedures are a growing trend in the UK. A range of devices are available for soft tissue augmentation, including injectable Poly-L-Lactic acid (PLLA). PLLA is used for soft tissue augmentation and is thought effective for the correction of contour deficiencies, facial wrinkles and in restoring subcutaneous volume in patients with HIV-associated lipoatrophy. Method In this case report, we present a rare but serious complication of subdermal injection of Poly-L-Lactic acid. A 45-year-old lady presented to our service approximately 24 hours after administration of self-sourced poly-L-Lactic acid. Results A 4cm ovaloid patch of full thickness skin necrosis over the zygomatic region was evident on presentation, with reactive/inflammatory changes in the adjacent skin. Vascular compromise is deemed the most likely cause, with loss of the transverse facial artery mapping to the area of necrosis. This patient was managed conservatively, with dressings and a prophylactic course of antibiotics. Conclusions Vascular compromise is a recognised and rare complication of subdermal injectable devices for facial soft tissue augmentation. The transverse facial artery branches from the superficial temporal artery within the substance of the parotid gland. Cadaveric and imaging studies alike demonstrate that the most common anatomical variant is a single TFA (70%), originating at the level of the temporofacial trunk of the facial nerve. It typically has a 5cm course, giving off on average 1.9 cutaneous perforators. This case highlights the importance of a detailed understanding of facial anatomy to ensure safe and effective placement of dermal fillers/devices.

Aim The use of augmented and mixed reality technology is a novel and rapidly developing field. This technology has generated significant interest in surgery, however the evidence supporting its proposed benefits is limited. This systematic review aims to critically appraise the intraoperative use of augmented and mixed reality technology to improve surgical outcomes in order to provide directions for future research. Method This systematic review is registered with PROSPERO (CRD42020205892) and was performed in adherence to PRISMA guidelines. Studies reporting primary data on surgical outcomes of the intraoperative use of augmented and mixed reality technology were included. A structured search of major literature databases was performed. Risk of bias was assessed following the guidance of the Cochrane Handbook. Results 68 studies met the inclusion criteria, with 63 reporting the intraoperative use of augmented reality technology and 5 reporting the use of mixed reality. The number and methodological quality of these studies is increasing. The intraoperative use of this technology has been demonstrated to reduce operative times, intraoperative blood loss and lengths of hospital admissions in specific settings. The widespread adoption of this technology faces the challenges of its cost, technical precision and integration into the surgical workflow. Conclusions The intraoperative use of augmented and mixed reality technology is an area of research still in its early stages, with an increasing number of methodologically robust studies on the subject. Current results suggest that the use of this technology is safe and, in certain applications, has the potential to significantly improve surgical and health-economic outcomes.

Fat hypertrophy is a less commonly known complication of autologous fat transfer. We present a 32-year-old female with left hemifacial atrophy associated with systemic sclerosis, who was treated with 7 fat transfer procedures to correct the facial asymmetry. A total of 236.5 mL of fat was injected to the hemiface over a 4-year period to achieve good symmetry. A progressively enlarging, painless, soft mass over the left parotid region was noted at 3 months after the final fat transfer procedure. Magnetic resonance imaging showed a markedly enlarged bulk of subcutaneous fat over the left cheek with no evidence of necrosis, edema, or pathologic enhancement. Concurrent weight gain was noted secondary to additional nutritional input. The patient’s aesthetic, symptomatic, and functional concerns led to the subsequent removal of 115 mL fat by liposuction. Level of Evidence: 5

Current techniques for breast reconstruction include an autologous-tissue flap or an implant-based procedure, although both can impose further morbidity. This systematic review aims to explore the existing literature on breast reconstruction using a tissue engineering approach; conducted with the databases Medline and Embase. A total of 28 articles were included, mainly comprising of level-5 evidence within vitroand animal studies focusing on utilizing scaffolds to support the migration and growth of new tissue; scaffolds can be either biological or synthetic. Biological scaffolds were composed of collagen or a decellularized tissue matrix scaffold. Synthetic scaffolds were primarily composed of polymers with customisable designs, adjusting the internal morphology and pore size. Implanting cells, including adipose-derived stem cells, with combined use of basic fibroblast growth factor has been studied in an attempt to enhance tissue regeneration. Lately, a level-4 evidence human case series was reported; successfully regenerating 210 mL of tissue using an arterio-venous pedicled fat flap within a tissue engineering chamber implanted on the chest wall. Further research is required to evaluate whether the use of cells and other growth factors could adjust the composition of regenerated tissue and improve vascularity; the latter a major limiting factor for creating larger volumes of tissue.

Raynaud's phenomenon (RP) is a common condition and causes pain, paraesthesia, ulceration and gangrene. Botulinum toxin A (Btx-A) is effective when injected via a digital palmar approach, in the treatment of severe RP. However, hand weakness resulting from lumbrical malfunction is a recognized complication. This study aimed to determine the effect of Btx-A injected via a dorsal approach.Forty patients received 100 units of Btx-A, injected across both hands via a dorsal approach. Each patient had a baseline, 6- and 12-week hand assessment and thermographic image (FLIR E60bx) performed for the study.Eighty-eight percent of patients reported an improvement in symptoms including reduction in pain, improved colour change with reduced swelling and edema at 6 weeks. Of these patients, 80% reported an improvement in cold intolerance with a reduction in the frequency and severity of Raynaud's attacks. There was a significant improvement in both the DASH score (p = 0.001), Kapandji score (p = 0.001) and hand strength (p 0.05). No patients reported weakness. Improvements in hand function and symptoms of RP were still evident at 12 weeks.Btx-A injected via a dorsal approach improves symptoms and reduces the number of RP. We have shown an effective non-surgical approach technique to treat RP.Key Points• Raynaud's phenomenon is a common vasospastic disorder of the digital vessels, which can cause severe pain, restrictions to hand function and ulceration.• Dorsal botulinum toxin type A injections can improve the symptoms of secondary Raynaud's phenomenon and hand function for approximately 3 months.

BACKGROUND Multimodality treatment for head and neck cancer leads to substantial functional and esthetic impairment mainly manifested as radiation-induced skin fibrosis (RIF) in combination with volumetric defects and reduction in neck mobility. This study assessed the impact of lipotransfer as part of secondary surgical procedure(s) in patients treated for head and neck malignancies. METHODS Retrospective analysis was performed between 2005 and 2016. All patients with a history of head and neck malignancy, multimodal treatment including at least surgery or radiotherapy, and at least 2-year disease-free survival were included. Thirty-eight patients (22 men, 16 women) matched the inclusion criteria. RESULTS Thirty seven (97%) reported esthetic and functional improvements in their RIF and volumetric defect at follow-up of 32 months. Major improvement in esthetic and functional outcome was reported by 24 (63%) patients and surgeons and minor by 13 patients and surgeons (34%) without causing any complications. Lipotransfer was also found to significantly improve patient's psychological health postoperatively as showed by significant improvements in Derriford Appearance Scale (DAS24), Short Form Health Survey (SF-36), and University of Washington Quality of Life Questionnaire (UW-QOL V4) scores (P

Trauma, congenital diseases, and cancer resection cause muscle deformities of the human facial muscle. Muscle defects are either treated with local or distal flaps if direct closure is not possible. However, such surgical interventions are limited by donor morbidity and limited tissue availability. Decellularized scaffolds provide alternative strategies for replacing and restoring missing facial muscle by creating scaffolds that mimic the native tissue. This study aimed to develop a protocol to decellularize human zygomaticus major muscle (ZMM) and masseter muscle (MM). Three protocols were assessed including a detergent-only treatment (DOT), detergent-enzymatic treatment (DET) protocol, and a third nondetergent nonenzymatic treatment protocol. Scaffolds were then characterized via histological, immunofluorescent, and quantitative techniques to assess which protocol provided optimal decellularization and maintenance of the extracellular matrix (ECM). The results demonstrated three cycles of DOT protocol consisting of 2% sodium dodecyl sulfate for 4 hr was optimal for decellularization for both ZMM and MM. After three cycles, DNA content was significantly reduced compared with native ZMM and MM (p < .05) with preservation of collagen and glycosaminoglycan content and ECM on histological analysis. DET and nondetergent nonenzymatic treatment protocols were unsuccessful in decellularizing the ZMM and MM with residual DNA content after four cycles and caused ECM disruption on histological analysis. All protocols did not impair the mechanical properties and supported human fibroblast growth. In conclusion, the DOT protocol is effective in producing human decellularized muscle scaffolds that maintain the ECM. Further investigation of detergent only decellurization techniques should be explored as a first step to create effective scaffolds for muscle tissue engineering.

Introduction Peripheral nerve injuries in children are uncommon and can be challenging to diagnose. There is a paucity of data on long-term sensorimotor and functional outcomes following surgical repair. We present a 12-year retrospective analysis of pediatric peripheral nerve repair with long-term functional outcomes. Materials and Methods We performed a retrospective analysis of pediatric patients with peripheral nerve injury requiring surgical repair. Clinical records were analyzed for procedure type, time to surgery, mechanism of injury, postoperative recovery, and complications. Results A total of 108 patients were identified and 87 patients were included. Out of 87 patients, 83 (95.4%) had partial or complete sensorimotor recovery at final follow-up and 4 did not improve. Minor complications occurred in 10.3% of patients, all resolved with conservative management. Mechanisms of injury were predominantly lacerations with sharp objects or crush injuries. Age at time of injury was inversely correlated with sensorimotor recovery, and time to surgical repair was not. Conclusion Surgical repair with long-term hand therapy results in excellent functional outcomes following pediatric peripheral nerve injury. A low threshold for exploration and repair should be used in instances of diagnostic uncertainty. Timing of surgical repair is dependent on a patient’s clinical presentation; however, repair within 48 hours is sufficient for optimal sensorimotor recovery.

Background Children born with a small or absent ear undergo surgical reconstruction to create a suitable replacement using rib cartilage. To overcome the donor site morbidity and long-term pain of harvesting rib cartilage, synthetic materials can be a useful alternative. Medpor, is the currently used synthetic polyethylene material to replace missing facial cartilage but unfortunately it has high levels of surgical complications including infection and extrusion, making it an unsuitable replacement. New materials for facial cartilage reconstruction are required to improve the outcomes of surgical reconstruction. This study has developed a new nanomaterial with argon surface modification for auricular cartilage replacement to overcome the complications with Medpor. Results Polyurethanes nanocomposites scaffolds (PU) were modified with argon plasma surface modification (Ar) and compared to Medpor in vitro and in vivo. Ar scaffolds allowed for greater protein adsorption than Medpor and PU after 48 h (p

Skeletal muscle is capable of regeneration following minor damage, more significant volumetric muscle loss (VML) however results in permanent functional impairment. Current multimodal treatment methodologies yield variable functional recovery, with reconstructive surgical approaches restricted by limited donor tissue and significant donor morbidity. Tissue-engineered skeletal muscle constructs promise the potential to revolutionise the treatment of VML through the regeneration of functional skeletal muscle. Herein, we review the current status of tissue engineering approaches to VML; firstly the design of biocompatible tissue scaffolds, including recent developments with electroconductive materials. Secondly, we review the progenitor cell populations used to seed scaffolds and their relative merits. Thirdly we review in vitro methods of scaffold functional maturation including the use of three-dimensional bioprinting and bioreactors. Finally, we discuss the technical, regulatory and ethical barriers to clinical translation of this technology. Despite significant advances in areas, such as electroactive scaffolds and three-dimensional bioprinting, along with several promising in vivo studies, there remain multiple technical hurdles before translation into clinically impactful therapies can be achieved. Novel strategies for graft vascularisation, and in vitro functional maturation will be of particular importance in order to develop tissue-engineered constructs capable of significant clinical impact.

BackgroundThe use of mixed and augmented reality in surgery is a novel and rapidly developing field. Augmented reality is a technology which overlays virtual images on to the real world and is supported by a variety of platforms. Mixed reality is a newer technology, which, in contrast, allows the user to interact with virtual objects projected onto the real world. These technologies have been employed in a range of surgical contexts and specialities and have generated significant public interest, however, the evidence supporting their proposed benefits is unclear. This systematic review aims to critically appraise the intraoperative use of mixed and augmented reality technologies to improve surgical outcomes and provide directions for future research. Methods This systematic review will follow the PRISMA guidelines and search the MEDLINE, EMBASE, the Cochrane Library electronic databases. All clinical studies reporting empirical data on the intraoperative use of augmented or mixed reality technologies will be eligible for inclusion. Identified studies will be screened for inclusion by three authors in parallel, with a fourth author resolving any discrepancies. Risk of bias will be assessed in accordance with Cochrane Handbook for Systematic Reviews of Interventions guidance. The quality of evidence for each outcome will be assessed using the GRADE approach.DiscussionThis will be the first systematic review performed with a specific focus on the use of mixed reality in surgery. If augmented and mixed reality are to become established tools in surgery, it is necessary to understand their use cases, advantages, limitations and cost-effectiveness. This is a young but rapidly evolving field; this synthesis of the current evidence base will provide direction for future research and development.Systematic Review RegistrationPROSPERO CRD42020205892

Oro-facial fibrosis presents a significant disease burden in patients with systemic sclerosis, but there remains no established treatment modality. Autologous fat grafting is a minimally invasive surgical procedure that is now increasingly recognised for its regenerative capacity, propagating an expansion of heterogeneous indications beyond volume restoration, including fibrotic diseases such as systemic sclerosis. We present a 42-year-old woman with oro-facial involvement of systemic sclerosis leading to severe limitation in mouth opening and closure, with marked retraction of the lower lip and gingival display. We describe the reconstructive journey over a 12-year period, where the antifibrotic effect of autologous fat grafting served as the basis on which a series of surgical procedures were performed to achieve functional and aesthetic improvement. Autologous fat grafting provides a novel treatment modality for oro-facial skin fibrosis, previously considered a non-treatable disease manifestation of systemic sclerosis.

Background. Three-dimensional (3D) photography provides a promising means of breast volumetry. Sources of error using a single-captured surface to calculate breast volume include inaccurate designation of breast boundaries and prediction of the invisible chest wall generated by computer software. An alternative approach is to measure differential volume using subtraction of 2 captured surfaces. Objectives. To explore 3D breast volumetry using the subtraction of superimposed images to calculate differential volume. To assess optimal patient positioning for accurate volumetric assessment. Methods. Known volumes of breast enhancers simulated volumetric changes to the breast (n = 12). 3D photographs were taken (3dMDtorso) with the subject positioned upright at 90° and posteriorly inclined at 30°. Patient position, breathing, distance and camera calibration were standardised. Volumetric analysis was performed using 3dMDvultus software. Results. A statistically significant difference was found between actual volume and measured volumes with subjects positioned at 90° ( P < .05). No statistical difference was found at 30° ( P = .078), but subsequent Bland–Altman analysis showed evidence of proportional bias ( P < .05). There was good correlation between measured and actual volumes in both positions (r = .77 and r = .85, respectively). Univariate analyses showed breast enhancer volumes of 195 mL and 295 mL to incur bias. The coefficient of variation was 5.76% for single observer analysis. Conclusion. Positioning the subject at a 30° posterior incline provides more accurate results from better exposure of the inferior breast. The subtraction tool is a novel method of measuring differential volume. Future studies should explore methodology for application into the clinical setting.

Highlights • Oro-facial fibrosis presents a significant disease burden in systemic sclerosis. • There is currently no treatment available for oro-facial fibrosis. • Autologous fat grafting is a novel therapeutic method for oro-facial fibrosis., Introduction Oro-facial fibrosis is a common and disabling manifestation of systemic sclerosis (SSc), causing a plethora of functional, aesthetic and social compromise, yet is without effective treatment. Autologous lipotransfer is an established minimally invasive surgical procedure that is postulated to exert anti-fibrotic effects by adipose-derived stem cells, and presents a novel method in the treatment of fibrotic conditions. This study aims to assess the safety and efficacy of autologous lipotransfer for facial involvement in SSc. Methods and analysis This is the first randomised controlled study with an open label design to assess autologous lipotransfer for oro-facial involvement in systemic sclerosis. The goals of this study are to assess the feasibility of using a range of quantitative and qualitative outcome measures to effectively measure disease severity and treatment outcome, and to assess patient acceptability for future multi-centre trials. A total of 50 participants will be randomised to a treatment or control group. The treatment group will receive autologous fat transfer to the peri-oral region by a single surgeon. Dermal fibroblasts and adipose-derived stem cells will be isolated from tissue samples. All outcome measures will be taken at baseline, then at 6 weeks, 3 months and 6 months from the time of intervention in the treatment arm, or from baseline in the control arm. Ethics and dissemination The study has ethical approval (REC reference 19/LO/0718). Results will be available to patients, patient user groups, clinicians and the public through presentations at national and international rheumatology conferences and published in peer reviewed journals. Trial registration Registered on ISRCTN registry (ISRCTN17793055).

We present a 48-year-old female patient who presented with features consistent with acquired partial lipodystrophy (APL) also known as ‘Barraquer-Simons syndrome’. It is a rare disease characterised by a gradual and progressive onset of lipoatrophy limited to the face, neck, upper limbs, thorax and abdomen and sparing the lower extremities. The resultant physical appearance can have significant psychosocial sequelae, further compounded by misdiagnosis and delay in recognition and management. Treatment is aimed at surgical correction of soft tissue destruction. Autologous fat transfer is an established plastic and reconstructive procedure that is safe and minimally invasive and can be used to reconstruct a variety of soft tissue defects and has shown to be an effective treatment modality in patients with APL.

An effective sterilisation technique that maintains structure integrity, mechanical properties, and biocompatibility is essential for the translation of new biomaterials to the clinical setting. We aimed to establish an effective sterilisation technique for a biodegradable (POSS-PCL) and nonbiodegradable (POSS-PCU) nanocomposite scaffold that maintains stem cell biocompatibility. Scaffolds were sterilised using 70% ethanol, ultraviolet radiation, bleach, antibiotic/antimycotic, ethylene oxide, gamma irradiation, argon plasma, or autoclaving. Samples were immersed in tryptone soya broth and thioglycollate medium and inspected for signs of microbial growth. Scaffold surface and mechanical and molecular weight properties were investigated. AlamarBlue viability assay of adipose derived stem cells (ADSC) seeded on scaffolds was performed to investigate metabolic activity. Confocal imaging of rhodamine phalloidin and DAPI stained ADSCs was performed to evaluate morphology. Ethylene oxide, gamma irradiation, argon plasma, autoclaving, 70% ethanol, and bleach were effective in sterilising the scaffolds. Autoclaving, gamma irradiation, and ethylene oxide led to a significant change in the molecular weight distribution of POSS-PCL and gamma irradiation and ethylene oxide to that of POSS-PCU (p

Macroscopic hydrogels are commonly used as injectable scaffolds or fillers, however they may easily obstruct blood vessels, which poses risks and limits their clinical use. In the present study, three types of hyaluronic acid (HA)-based hydrogel micro-particles with non-covalent, covalent semi-interpenetrating and conventional 3D molecular networks, have been designed, fabricated and characterized. The micro-particles are spherical, biconcave or irregular in shape and their diameter ranged between 2.5 and 3.5 µm; their suspensions exhibit a tuneable viscosity, shear-thinning behaviour, dynamic stability and dispersity in microfluidic flow as a result of their specific particulate nature, providing thus a well-controlled injectable platform. Hydrogel particle suspensions also demonstrate an enhanced safety profile, in terms of the dispersity, cell safety, and hemocompatibility. In addition, Rhodamine 6G has successfully been loaded and released from the particles as a model for drug delivery. Functionalisation of hydrogel microparticles using synthetic polymers has been proven to be a cost-effective way to achieve desirable rheological properties and flow dynamic stability with improved physicochemical properties and biocompatibility in vitro, showing promise as a multifunctional biomedical material for various advanced surgical devices and therapies.

Objective The use of 3-dimensional (3D) printing in medicine has rapidly expanded in recent years as the technology has developed. The potential uses of 3D printing are manifold. This article provides a systematic review of the uses of 3D printing within surgical training and assessment. Methods A structured literature search of the major literature databases was performed in adherence to PRISMA guidelines. Articles that met predefined inclusion and exclusion criteria were appraised with respect to the key objectives of the review and sources of bias were analysed. Results Overall, 49 studies were identified for inclusion in the qualitative analysis. Heterogeneity in study design and outcome measures used prohibited meaningful meta-analysis. 3D printing has been used in surgical training across a broad range of specialities but most commonly in neurosurgery and otorhinolaryngology. Both objective and subjective outcome measures have been studied, demonstrating the usage of 3D printed models in training and education. 3D printing has also been used in anatomical education and preoperative planning, demonstrating improved outcomes when compared to traditional educational methods and improved patient outcomes, respectively. Conclusions 3D printing technology has a broad range of potential applications within surgical education and training. Although the field is still in its relative infancy, several studies have already demonstrated its usage both instead of and in addition to traditional educational methods.

Objective Visualization tools are essential for effective medical education, to aid students understanding of complex anatomical systems. Three dimensional (3D) printed models are showing a wide-reaching potential in the field of medical education, to aid the interpretation of 2D imaging. This study investigates the use of 3D-printed models in educational seminars on cleft lip and palate, by comparing integrated “hands-on” student seminars, with 2D presentation seminar methods. Setting Cleft lip and palate models were manufactured using 3D-printing technology at the medical school. Participants Sixty-seven students from two medical schools participated in the study. Design The students were randomly allocated to 2 groups. Knowledge was compared between the groups using a multiple-choice question test before and after the teaching intervention. Group 1 was the control group with a PowerPoint presentation-based educational seminar and group 2 was the test group, with the same PowerPoint presentation, but with the addition of a physical demonstration using 3D-printed models of unilateral and bilateral cleft lips and palate. Results The level of knowledge gained was established using a preseminar and postseminar assessment, in 2 different institutions, where the addition of the 3D-printed model resulted in a significant improvement in the mean percentage of knowledge gained (44.65% test group; 32.16%; control group; p = 0.038). Student experience was assessed using a postseminar survey, where students felt the 3D-printed model significantly improved the learning experience (p = 0.005) and their visualization (p = 0.001). Conclusions This study highlights the benefits of the use of 3D-printed models as visualization tools in medical education and the potential of 3D-printing technology to become a standard and effective tool in the interpretation of 2D imaging.

Lipotransfer for soft tissue filling is a well-established plastic and aesthetic surgical technique. Elective fat grafting is considered a safe and well-tolerated procedure. Coleman and others have reported that fat grafting may have tissue regenerative properties and not only serve as a soft tissue filler. There have been reports from our group and others that it may improve fibrosis secondary to many different pathological aetiologies including scleroderma, burn injury, lichen sclerosis, graft vs host disease, and radiation. The mechanism of action remains unclear but has been postulated that is adipose derived stem cells (ADSCs) related. Lipoaspirate has been characterised and shown to contain several cell populations including fibroblasts, endothelial cells, and ADSCs. The ADSCs have shown to secrete angiogenic, immunodulatory, and antiapoptotic factors as well as proliferate and differentiate into different cell types similarly to other stem cell sources. We have shown that ADSCs are functionally different in scleroderma patients but despite this lipotransfer produces a significant reversal in the effects of fibrosis in these patients. The advantage of lipoaspirate containing a valuable source of regenerative properties, ease of access, isolation, and processing may serve a significant future role in the treatment of fibrotic conditions.

Graphical abstract, Human adipose derived stem cells (ADSCs) are being explored for the repair of craniofacial defects due to their multi-differentiation potential and ease of isolation and expansion. Crucial to using ADSCs for craniofacial repair is the availability of materials with appropriate biomechanical properties that can support their differentiation into bone and cartilage. We tested the hypothesis that different modifications of chemical groups on the surface of a nanocomposite polymer could increase human ADSC adhesion and selectively enhance their osteogenic and chondrogenic differentiation. We show that the COOH modification significantly promoted initial cell adhesion and proliferation over 14 days compared to NH2 surfaces. Expression of focal adhesion kinase and vinculin was enhanced after plasma surface polymerisation at 24 h. The COOH modification significantly enhanced chondrogenic differentiation as indicated by up-regulation of aggrecan and collagen II transcripts. In contrast, NH2 group functionalised scaffolds promoted osteogenic differentiation with significantly enhanced expression of collagen I, alkaline phosphatase and osteocalcin both at the gene and protein level. Finally, chorioallantoic membrane grafting demonstrated that both NH2 and COOH functionalised scaffolds seeded with ADSCs were biocompatible and supported vessel ingrowth apparently to a greater degree than unmodified scaffolds. In summary, our study shows the ability to direct ADSC chondrogenic and osteogenic differentiation by deposition of different chemical groups through plasma surface polymerisation. Hence this approach could be used to selectively enhance bone or cartilage formation before implantation in vivo to repair skeletal defects. Statement of Significance Human adipose derived stem cells (hADSCs) are an exciting stem cell source for regenerative medicine due to their plentiful supply and ease of isolation. However, the optimal environmental cues to direct stem cells towards certain lineages change have to has not been identified. We have shown that by modifying the surface of the scaffold with specific chemical groups using plasma surface polymerisation techniques we can control ADSCs differentiation. This study shows that ADSCs can be differentiated towards osteogenic and chondrogenic lineages on amine (NH2) and carboxyl (COOH) modified scaffolds respectively. Plasma polymerisation can be easily applied to other biomaterial surfaces to direct stem cell differentiation for the regeneration of bone and cartilage.

Oro-facial fibrosis in systemic sclerosis (Scleroderma;SSc) has a major impact on mouth function, facial appearance, and patient quality of life. Lipotransfer is a method of reconstruction that can be used in the treatment of oro-facial fibrosis. The effect of this treatment not only restores oro-facial volume but has also been found to reverse the effects of oro-facial fibrosis. Adipose derived stem cells (ADSCs) within the engrafted adipose tissue have been shown to be anti-fibrotic in SSc and are proposed as the mechanism of the anti-fibrotic effect of lipotransfer. A cohort of 62 SSc patients with oro-facial fibrosis were assessed before and after stem cell enriched lipotransfer treatment. Clinical evaluation included assessment of mouth function using a validated assessment tool (Mouth Handicap in Systemic Sclerosis Scale-MHISS), validated psychological measurements and pre and post-operative volumetric assessment. In addition, to understand the mechanism by which the anti-fibrotic effect of ADSCs occur, SSc derived fibroblasts and ADSCs from this cohort of patients were co-cultured in direct and indirect culture systems and compared to monoculture controls. Cell viability, DNA content, protein secretion of known fibrotic mediators including growth factor- β1 (TGF β-1) and connective tissue growth factor (CTGF) using ELISA analysis and fibrosis gene expression using a fibrosis pathway specific qPCR array were evaluated. Mouth function (MHISS) was significantly improved (6.85±5.07) (p

Upper limb muscle reconstruction is required following cancer resection, trauma, and congenital deformities. Current surgical reconstruction of the muscle involves local, regional and free flaps. However, muscle reconstruction is not always possible due to the size of the defect and functional donor site morbidity. These challenges could be addressed with the production of scaffolds composed of an extracellular matrix (ECM) derived from decellularized human skeletal muscle. This study aimed to find an optimal technique to decellularize a flexor digitorum superficialis muscle. The first two protocols were based on a detergent only (DOT) and a detergent-enzymatic protocol (DET). The third protocol avoided the use of detergents and proteolytic enzymes (NDNET). The decellularized scaffolds were characterized using qualitative techniques including histological and immunofluorescent staining and quantitative techniques assessing deoxyribonucleic acid (DNA), glycosaminoglycan (GAG), and collagen content. The DOT protocol consisting of 2% SDS for 4 hours was successful at decellularizing human FDS, as shown by DNA content assay and nuclei immunofluorescence staining. The DOT protocol maintained the microstructure of the scaffolds as shown by Masson's trichrome staining and collagen and GAG content. DET and NDNET protocols maintained the ECM, but were unsuccessful in removing all DNA content after two cycles of decellularization. Decellularization of skeletal muscle is a viable option for muscle reconstruction using a detergent only technique for upper limb defects. Further testing in vivo will assess the effectiveness of decellularized scaffolds for upper limb muscle skeletal tissue engineering.

Recently, adipose-derived stem cells (ASCs), obtained from fresh human lipoaspirate, have shown promise as immunomodulatory agents having demonstrated immunosuppressive functionality both in vitro and in vivo. A number of researchers have described the isolation of ASCs through the enzymatic digestion of fat samples, followed by a number of purification steps, involving centrifugation and filtration. Here, we utilize a standard isolation technique, with the added purification of putative ASCs by fluorescence activated cell sorting (FACS). ASCs are an extremely valuable resource in clinical applications, including reconstruction, regeneration, and investigations into immune activity. This method could be used to isolate and purify ASCs for such downstream applications.

Background: Natural cartilage regeneration is limited after trauma or degenerative processes. Due to the clinical challenge of reconstruction of articular cartilage, research into developing biomaterials to support cartilage regeneration have evolved. The structural architecture of composition of the cartilage extracellular matrix (ECM) is vital in guiding cell adhesion, migration and formation of cartilage. Current technologies have tried to mimic the cell’s nanoscale microenvironment to improve implants to improve cartilage tissue repair. Methods: This review evaluates nanoscale techniques used to modify the implant surface for cartilage regeneration. Results: The surface of biomaterial is a vital parameter to guide cell adhesion and consequently allow for the formation of ECM and allow for tissue repair. By providing nanosized cues on the surface in the form of a nanotopography or nanosized molecules, allows for better control of cell behaviour and regeneration of cartilage. Chemical, physical and lithography techniques have all been explored for modifying the nanoscale surface of implants to promote chondrocyte adhesion and ECM formation. Conclusion: Future studies are needed to further establish the optimal nanoscale modification of implants for cartilage tissue regeneration.

Background:Natural bone is a complex and hierarchical structure. Bone possesses an extracellular matrix that has a precise nano-sized environment to encourage osteoblasts to lay down bone by directing them through physical and chemical cues. For bone tissue regeneration, it is crucial for the scaffolds to mimic the native bone structure. Nanomaterials, with features on the nanoscale have shown the ability to provide the appropriate matrix environment to guide cell adhesion, migration and differentiation.Methods:This review summarises the new developments in bone tissue engineering using nanobiomaterials. The design and selection of fabrication methods and biomaterial types for bone tissue engineering will be reviewed. The interactions of cells with different nanostructured scaffolds will be discussed including nanocomposites, nanofibres and nanoparticles.Results:Several composite nanomaterials have been able to mimic the architecture of natural bone. Bioceramics biomaterials have shown to be very useful biomaterials for bone tissue engineering as they have osteoconductive and osteoinductive properties. Nanofibrous scaffolds have the ability to provide the appropriate matrix environment as they can mimic the extracellular matrix structure of bone. Nanoparticles have been used to deliver bioactive molecules and label and track stem cells.Conclusion:Future studies to improve the application of nanomaterials for bone tissue engineering are needed.