Surgical Handling Research Articles

Pattern of workplace violence against doctors practising modern medicine and the subsequent impact on patient care, in India.

IntroductionThe incidents of violence against doctors, leading to grievous injury and even death, seem to be on an increasing trend in recent years. There is a paucity of studies on workplace violence against doctors and its effect, in India. The present study was conducted to assess workplace violence faced by doctors, its effect on the psycho-social wellbeing of the treating doctor and, subsequently, on patient management.MethodsThe present nationwide cross-sectional study was conducted from November 2019 –April 2020. The sample size was calculated assuming the prevalence of workplace violence as 50%, with 20% non-response. Doctors, working in private and/or public set-up, with ≥1 year clinical experience, were included. A pre-tested study tool- Google form—was sent to study participants via social media platforms. The Microsoft Excel spreadsheet was downloaded from google drive and data was analysed using STATA-12 statistical software.ResultsA total of 617 responses were received from doctors all over India; out of which 477 (77.3%) doctors had ever faced workplace violence. “Actual or perceived non-improvement or deterioration of patient’s condition" (40.0%), followed by “perception of wrong treatment given” (37.3%) were the main causes of workplace violence; and the family members/relatives were the major perpetrators (82.2%). More than half of the participants reported “loss of self-esteem”, “feeling of shame” and “stress/depression/anxiety/ideas of persecution” after the incident. Management by surgical interventions (p-value<0.001) and handling of emergency/complicated cases (p-value<0.001) decreased significantly with an increase in severity of workplace violence; while the suggestion of investigations and referrals increased (p-value<0.001).ConclusionsWorkplace violence has a significant effect on the psycho-social well-being of doctors, as well as on patient management; which may escalate discontent and distrust among the general public, thereby increasing incidents of workplace violence—in a self-propagating vicious cycle.

Ceramic Scaffolds in a Vacuum Suction Handle for Intraoperative Stromal Cell Enrichment.

During total joint replacement, high concentrations of mesenchymal stromal cells (MSCs) are released at the implantation site. They can be found in cell–tissue composites (CTC) that are regularly removed by surgical suction. A surgical vacuum suction handle was filled with bone substitute granules, acting as a filter allowing us to harvest CTC. The purpose of this study was to investigate the osteopromotive potential of CTC trapped in the bone substitute filter material during surgical suction. In the course of 10 elective total hip and knee replacement surgeries, β-tricalcium-phosphate (TCP) and cancellous allograft (Allo) were enriched with CTC by vacuum suction. Mononuclear cells (MNC) were isolated from the CTC and investigated towards cell proliferation and colony forming unit (CFU) formation. Furthermore, MSC surface markers, trilineage differentiation potential and the presence of defined cytokines were examined. Comparable amounts of MNC and CFUs were detected in both CTCs and characterized as MSC‰ of MNC with 9.8 ± 10.7‰ for the TCP and 12.8 ± 10.2‰ for the Allo (p = 0.550). CTCs in both filter materials contain cytokines for stimulation of cell proliferation and differentiation (EGF, PDGF-AA, angiogenin, osteopontin). CTC trapped in synthetic (TCP) and natural (Allo) bone substitute filters during surgical suction in the course of a joint replacement procedure include relevant numbers of MSCs and cytokines qualified for bone regeneration.

Variation in abdominal wall closure techniques in lower transverse incisions: a nationwide survey across specialties.

Lower transverse abdominal incisions are typically used by obstetricians/gynecologists and colorectal surgeons. The suture technique and choice of material when closing the abdomen is an essential factor to decrease the risk of incisional hernia. We conducted a nationwide survey among obstetricians/gynecologists and colorectal surgeons investigating the surgical handling of the fascia, rectus muscle, subcutis, peritoneum, and skin, in lower transverse incisions. All departments of obstetrics/gynecology and departments of surgery performing colorectal surgery in Denmark were invited to participate. An online questionnaire was sent to consultant obstetricians/gynecologists and colorectal surgeons. The survey consisted of demographic information together with questions on surgical details. The study was reported according to STROBE guidelines. A total of 252 (64.5%) consultants provided a complete response to the survey. We found that 98.0% of the colorectal surgeons and 65.8% of the obstetricians/gynecologists used monofilament suture when closing the fascia. The majority of the colorectal surgeons used continuous suture and small bites technique. This was only the case for half of the obstetricians/gynecologists. Approximately two thirds of the colorectal surgeons and one third of the OB/GYN used the suture length to wound length ratio > 4:1. Furthermore, we found significant differences between the groups in the handling of subcutis, peritoneum, and skin. We found significant variation in abdominal wall closure techniques in lower transverse incisions. Disagreement between the current guidelines within the specialties together with insufficient evidence on the closure of lower transverse incisions emphasizes the need for education as well as further studies.

Expanded endoscopic endonasal approach for extending suprasellar and third ventricular lesions.

Expanded endonasal approaches can provide direct access to the midline skull base from the anterior cranial fossa to the ventral foramen magnum. Surgical strategies of bone drilling, dural opening, and intradural dissection can determine the area of surgical exposure and instrument handling, affecting the safety of devascularizing/debulking suprasellar tumors. We describe an expanded endoscopic endonasal approach for suprasellar lesions, with stepwise image-guided dissections highlighting surgical pearls and pitfalls to enhance surgical safety. This article presents transnasal intra-third-ventricular anatomy from trans-tuber cinereum, and trans-lamina terminalis approaches, comparing subchiasmatic and suprachiasmatic trajectories. The rostral extension via endoscopic endonasal transsellar-transtubercular-transplanum approaches can provide a safe and feasible route for suprasellar lesions, in subchiasmatic, suprachiasmatic, and intraventricular regions.

Enhanced PeriOperative Care and Health protection programme for the prevention of surgical site infections after elective abdominal surgery (EPOCH): study protocol of a randomised controlled, multicentre, superiority trial

IntroductionSurgical site infections (SSI) are a common postoperative complication. During the development of the new WHO guidelines on SSI prevention, also in the Netherlands was concluded that perioperative care could...

Advanced three-dimensionally engineered simulation model for aortic valve and proximal aorta procedures.

A 3-dimensionally (3D) engineered model for simulation of aortic valve and proximal aortic procedures is a reliable tool both for training young surgeons and for simulating complex cases. To achieve a realistic simulation, the artificial model should reproduce the angles and orientations of the cardiac structures based on the patient's anatomical condition, reproduce tissue mechanical characteristics and be easy to obtain and easy to use. The goal of the study was the production and validation of realistic training models, based on the patient's actual anatomical characteristics, to provide training for aortic valve procedures. An anatomical model was manufactured using 3D printing and silicone casting. The digital anatomical model was obtained by segmenting computed tomography imaging. The segmented geometrical images were processed and a casting mould was designed. The mould was manufactured on a 3D printer. Silicone was cast into the mould; after curing, the finished model was ready. The realistic reproduction was evaluated by mechanical hardness tests and a survey by cardiac surgeons. Six 3D silicone models were produced that represented the patient's anatomy including aortic valve leaflets, aortic root with coronary ostia, ascending aorta and proximal arch. Aortic valve replacement was performed, and 100% of the participants evaluated the model in a survey as perfectly reproducing anatomy and surgical handling. We produced a realistic, cost-effective simulator for training purposes and for simulation of complex surgical cases. The model reproduced the real angulation and orientation of the aortic structures inside the mediastinum, permitting a real-life simulation of the desired procedure. This model offers opportunities to simulate various surgical procedures.

SPARC: A Carbon Fiber Nerve Electrode Appropriate for Chronic Recording

State‐of‐the‐art intraneural peripheral nerve electrodes are large, silicon‐based structures that can cause substantial tissue response and are ill‐suited for recording from small autonomic nerves. The focus of this work is to adapt our minimally‐scarring carbon fiber brain electrodes to a chronic intraneural nerve array. The objective of this study is to increase the durability of the carbon fiber electrodes to withstand the surgical handling necessary for nerve implantation, while maintaining a cellular scale electrode that can insert through the outer epineurium layer of peripheral nerves. Toward that end, we embedded carbon fibers in silicone to increase robustness, sharpened the fibers to penetrate epineurium, and tested fibers coated with poly(3,4‐ethylene‐dioxythiophene):sodium p‐toluenesulfonate (PEDOT:pTS) in vivo.We tested the durability of carbon fibers by embedding uninsulated fibers in a body of silicone and inducing a 90‐degree bend to simulate the expected shear forces seen during surgery. We found that fibers of 175μm length were robust to thousands of bend cycles. After 3000 bends, 15 of 16 fibers remained intact. We blunt cut carbon fibers using a 532nm green laser and inserted fibers into silicone of stiffness similar to epineurium to determine a length for in vivo testing. We found that blunt fibers reliably insert into silicone without breaking when less than 200μm in length (N=8 fibers). We hypothesized that sharpened fibers would insert into tissue more easily, and therefore sharpened fibers with a 5mm butane flame when protruding from the surface of water. The dimensions of sharpened fibers were 224μm in length with 147μm of exposed carbon and a tip angle of 72 degrees (N=24 fibers).We inserted functionalized sharpened carbon fibers coated with PEDOT:pTS into peroneal and cervical vagus nerves of anesthetized rats (N=5 arrays, 71 fibers, 7 animals). In all experiments, we observed that the sharpened carbon fiber electrodes penetrated the epineurium for successful insertion. The average 1kHz impedance of coated fibers prior to and upon insertion was 38kΩ and 56kΩ, respectively. In both cases, the Z1kHz of roughly 90% of fibers measured below 100kΩ. We recorded spontaneous and evoked neural activity in each experiment and are analyzing the data for discernable single units. We also inserted sharpened fibers into anesthetized feline sacral dorsal root ganglia (N=3) and confirmed insertion with evoked neural recordings and 1kHz impedances (Z=59kΩ).This work shows that the durable nature of carbon fibers embedded in silicone allows them to withstand surgical handling and insert into various types of nerves. Our next step will be the fabrication of an array for chronic implantation.Support or Funding InformationNIH OT2OD024907, NINDS U01NS094375, NINDS UF1NS107659, NSF 1707316

Evaluation of 1-mm-diameter endothelialized dense collagen tubes in vascular microsurgery.

Although much progress has been made in engineering vascular grafts for large- and small-diameter arterial repair or bypass, the extension of these results to the microsurgical size scale has been challenging. Here, we evaluated the use of dense collagen tubes (outer diameter 1 mm, inner diameter 0.5 mm) for vascular microsurgery as interpositional grafts to the femoral artery of Lewis rats. These tubes were formed by dehydrating tubular collagen gels around a mandrel, crosslinking them with genipin, seeding with syngeneic endothelial cells, and culturing before implantation by suture anastomosis. The retention of a confluent endothelial lining inside the tubes after mock surgical handling depended strongly on the crosslinker concentration and culture time. Optimized preparation conditions enabled retention of endothelium after mock surgical handling in ~80% of tubes and maintenance of patency 7 days after implantation in ~40% of grafts. Histological analysis showed the development of granulation tissue and the presence of CD31-positive structures on the inner and outer surfaces of implants. This study provides a proof-of-principle demonstration that endothelialized dense collagen tubes can remain patent for up to 7 days after vascular microsurgery, and points to the importance of mild scaffold crosslinking for maintaining firm endothelial adhesion.

Anesthesia in Combination with Propofol Increases Disease-Free Survival in Bladder Cancer Patients Who Undergo Radical Tumor Cystectomy as Compared to Inhalational Anesthetics and Opiate-Based Analgesia

Background:The effect of anesthetic techniques on cancer recurrence has been the subject of intensive research in the past years, as it affects a large proportion of the population. The use of opioids and halogenated agents in cancer patients during the perioperative period may be related to higher rates of cancer recurrence and reduced disease-free survival. Methods:This was a prospective study. The sample was composed of 100 patients who underwent a radical cystectomy for infiltrating bladder cancer in a reference center. We compared disease-free survival associated with combined anesthesia versus opiate-based analgesia. The relationship between the administered hypnotic and disease-free survival was also investigated. Results:The median disease-free survival of the patients who received combined anesthesia was 585 (240–1,005) days versus 210 (90–645) days in the other group. A significant difference was observed between the two groups (p = 0.01). Combined analysis of all groups revealed significant differences in disease-free survival between patients who received combined anesthesia with propofol (510 [315–1,545] disease-free days) and those who received sevoflurane and opioids (150 [90–450] disease-free days) (p = 0.02). Conclusions:Anesthesia may play a crucial role in tumor relapse, as it is administered at the moment of the greatest risk of dissemination: surgical handling of the tumor. Opioids and volatile agents have been related to an increased risk for cancer recurrence. We compared the use of propofol + local anesthesia versus sevoflurane + opioids and also found that disease-free survival was longer among patients who received propofol + local anesthesia. Disease-free survival increases with the use of propofol in combination with epidural anesthesia in patients who undergo surgery for infiltrating bladder cancer.

In Vitro Evaluation and Transplantation of Human Corneal Endothelial Cells Cultured on Biocompatible Carriers

Corneal transplantation is currently the only effective treatment option for dysfunctional corneal endothelial cells (CEC). In this study, we test in vitro the surgical potential of cultivated human corneal endothelial cells (hCEC) on human anterior lens capsule (HALC), LinkCell™ bioengineered collagen sheets of 20-µm thickness (LK20), and denuded Descemet membrane (dDM) as tissue-engineered grafts for Descemet membrane (DM) endothelial keratoplasty (DMEK) to bypass the problem of donor tissue availability. Primary hCEC cultured on all carriers formed a monolayer of tightly packed cells with a high cell viability rate (96% ± 4%). hCEC on HALC and LK20 showed unremarkable expression of zonula occludens-1 (ZO-1) and Na+/K+-adenosine triphosphatase (ATPase), while Na+/K+-ATPase expression of cells seeded on dDM was mainly cytoplasmic. All hCEC–carrier constructs were evaluated by simulating DMEK surgery in vitro using a human donor cornea without DM mounted on an artificial anterior chamber (AC) and a regular DMEK-graft used as a surgical reference model. During in vitro surgery, hCEC–HALC constructs behaved most similarly to a DMEK-graft during implantation and unfolding, showing good adhesion to the bare stroma. On the other hand, hCEC–LK20 and hCEC–dDM constructs required some additional handling because of challenges related to the surgical procedure, although they were both successfully unfolded and implanted in the artificial AC. The hCEC–dDM constructs showed similar graft adherence as hCEC–HALC constructs, while adherence of hCEC–LK20 constructs was less effective. After the in vitro surgery, the estimated area populated by viable cells on the hCEC–HALC and hCEC–LK20 constructs was ∼83% and ∼67%, respectively. Overall, hCEC–HALC constructs behaved most similarly to a DMEK-graft during in vitro DMEK surgery, while graft adhesion and surgical handling, respectively, are parameters still requiring optimization for hCEC–LK20 and hCEC–dDM constructs.

Surgical smoke; an occupational hazard.

Surgical smoke is part of the environment during operative and invasive procedures. Electric diathermy is a very important tool for a surgeon and is used in every surgical treatment nowadays. It assists the surgeon to dissect the tissue or enables securing haemostasis in lesser time and with larger delicacy. But at the same time, it has harmful effects on surgeon as well as patients. Although there is a substantial amount of evidence and guidelines from various authors and societies, yet there are no clear policies and preventive measures towards surgical smoke handling. This article presents potential harmful effects of surgical smoke and aims to build guidelines for the surgical personnel based on current evidence in literature.

Biomimetic peptide enriched nonwoven scaffolds promote calcium phosphate mineralisation.

Cell-free translational strategies are needed to accelerate the repair of mineralised tissues, particularly large bone defects, using minimally invasive approaches. Regenerative bone scaffolds should ideally mimic aspects of the tissue's ECM over multiple length scales and enable surgical handling and fixation during implantation in vivo. Leveraging the knowledge gained with bioactive self-assembling peptides (SAPs) and SAP-enriched electrospun fibres, we presented a cell free approach for promoting mineralisation via apatite deposition and crystal growth, in vitro, of SAP-enriched nonwoven scaffolds. The nonwoven scaffold was made by electrospinning poly(ε-caprolactone) (PCL) in the presence of either peptide P11-4 (Ac-QQRFEWEFEQQ-Am) or P11-8 (Ac QQRFOWOFEQQ-Am), in light of the polymer's fibre forming capability and its hydrolytic degradability as well as the well-known apatite nucleating capability of SAPs. The 11-residue family of peptides (P11-X) has the ability to self-assemble into β-sheet ordered structures at the nano-scale and to generate hydrogels at the macroscopic scale, some of which are capable of promoting biomineralisation due to their apatite-nucleating capability. Both variants of SAP-enriched nonwoven used in this study were proven to be biocompatible with murine fibroblasts and supported nucleation and growth of apatite minerals in simulated body fluid (SBF) in vitro. The fibrous nonwoven provided a structurally robust scaffold, with the capability to control SAP release behaviour. Up to 75% of P11-4 and 45% of P11-8 were retained in the fibres after 7 day incubation in aqueous solution at pH 7.4. The encapsulation of SAP in a nonwoven system with apatite-forming as well as localised and long-term SAP delivery capabilities is appealing as a potential means of achieving cost-effective bone repair therapy for critical size defects.

Anesthesia for oral surgeries during the COVID-19 pandemic.

The severe acute respiratory syndrome corona virus 2(SARS-Cov2) virus replicates in the nasal cavity, nasopharynx, and the oropharynx. During oral surgery, the risk of viral transmission is high during instrumentation in these areas, while performing airway management procedures, the oral surgery itself, and related procedures. During the corona virus disease 2019 (COVID-19) pandemic, patients with an oral pathology usually present for emergency procedures. However, patients with oral cancer, being a semi-emergency, may also present for diagnostic and therapeutic procedures. When elective surgeries are resumed, these patients will come to the operating room. In asymptomatic patients, the false-negative rate can be as high as 30%. These patients are a source of infection to the healthcare workers and other patients. This mandates universal precautions to be taken for all patients presenting for surgery. Lesions along the airway, distorted anatomy secondary to cancer therapy, shared airway with the surgeon, surgical handling of the airway and the risk of bleeding, make airway management challenging in these patients, especially while wearing personal protective equipment. Airway management procedures, oral surgery, use of cautery, and other powered surgical instruments in the aero digestive tract, along with constant suctioning are a source of significant aerosol generation, further adding to the risk of viral transmission. Maintaining patient safety, while protecting the healthcare workers from getting infected during oral surgery is paramount. Meticulous advance planning and team preparation are essential. In this review, we discuss the challenges and recommendations for safe anesthesia practice for oral surgery during the COVID-19 pandemic, with special emphasis on risk mitigation.

Surgical handling of uveitic membranes in pediatric phakic eyes.

Surgical handling of uveitic membranes in pediatric phakic eyes.

Pre- and intraoperative acoustic and functional assessment of the novel APrevent\xae VOIS implant during routine medialization thyroplasty

PurposePersistent unilateral vocal fold paralysis (UFVP) with glottal insufficiency often requires type I medialization thyroplasty (MT). Previous implants cannot be adjusted postoperatively if necessary. The newly developed APrevent® VOIS implant (VOIS) can provide postoperative re-adjustment to avoid revision MT. The objective of this pilot study is to evaluate the VOIS intraoperatively concerning voice improvement, surgical feasibility and device handling.MethodsDuring routine MT, VOIS was applied short time in eight patients before the regular implantation of the Titanium Vocal Fold Medialization Implant (TVFMI™). In all patients, perceptual voice sound analysis using R(oughness)–B(reathiness)–H(oarseness)-scale, measurement of M(aximum)–P(honation)–T(ime) and glottal closure in videolaryngoscopy were performed before and after implanting VOIS/TVFMI™. Acoustic analyses of voice recordings were performed using freeware praat. Surgical feasibility, operative handling and device fitting of VOIS and TVFMI™ were assessed by the surgeon using V(isual)-A(nalog)-S(cale). Data were statistically analyzed with paired t test.ResultAll patients showed significant improvement of voice sound parameters after VOIS/TVFMI™ implantation. The mean RBH-scale improved from preoperative R = 2.1, B = 2.3, H = 2.5 to R = 0.6, B = 0.3, H = 0.8 after VOIS and R = 0.5, B = 0.3, H = 0.8 after TVFMI™ implantation. The mean MPT increased from preoperative 7.9 to 14.6 s after VOIS and 13.8 s after TVFMI™ implantation. VOIS/TVFMI™ achieved complete glottal closure in 7/8 patients. The satisfaction with intraoperative device fitting and device handling of VOIS was as good as that of TVFMI™.ConclusionThe novel APrevent® VOIS implant showed similar intraoperative voice improvement compared to routinely used TVFMI™ without adverse device events and with safe device fitting.

In vitro expanded corneal endothelial cell sheets: towards a new therapeutic approach

AbstractCorneal transplantation is currently the only effective treatment solution to restore corneal clarity in patients with endothelial disorders. Descemet membrane endothelial keratoplasty (DMEK) is the most recent corneal transplantation technique that selectively replaces only Descemet membrane (DM) and endothelium with the same layers of a healthy donor. However, its application is limited by shortage of high‐quality healthy donor tissue. In order to increase the pool of endothelial grafts, new strategies have been developed, which include surgical‐based and tissue‐engineering based approaches.Tissue‐engineered approaches such as endothelial cell sheet transplantation and cell injection rely on the in‐vitro expansion of cultured corneal endothelial cells (CEC). For endothelial cell sheet transplantation suitable cell carriers are required, which could either be natural carriers (e.g. human anterior lens capsules (HALC)) or bioengineered matrices (e.g. 20 µm thick collagen‐based carriers (LK20)).Within the ARREST BLINDNESS project, CEC were cultured on different carriers and the suitability of the cell‐carrier sheets as tissue‐engineered grafts for DMEK‐like procedures was evaluated by performing in‐vitro surgeries. Upon in‐vitro DMEK surgery, CEC‐HALC sheets behaved similarly to a standard DMEK‐graft on all scored aspects such as graft implantation, unfolding and adherence to bare stroma, whereas graft adhesion and surgical handling, respectively, are issues that still need to be addressed for CEC‐LK20 and CEC‐‘denuded DM’ sheets. First results of in‐vivo tests in an animal model will be presented as well as measures to approach legislative issues.

In vitro evaluation and transplantation of human corneal endothelial cells cultured on biocompatible carriers

AbstractPurposeTo test in vitro the surgical potential of cultivated human corneal endothelial cells (hCEC) on human anterior lens capsule (HALC), bioengineered collagen sheets and denuded Descemet membrane (dDM) as tissue‐engineered grafts for Descemet membrane endothelial keratoplasty (DMEK).MethodsPrimary hCEC were seeded onto HALC, LinkCell™ bioengineered matrices of 20µm thickness (LK20), and dDM. Cell morphology, viability, and proliferation were assessed by light microscopy, cell viability assay, and immunohistochemistry. All hCEC‐carrier constructs were evaluated by simulating DMEK surgery in vitro using an artificial anterior chamber (AC) and a human donor cornea, without DM, with a regular DMEK graft as control.ResultsPrimary hCEC cultured on all carriers formed a monolayer of tightly packed cells with a high cell viability rate (96±4%) and expression of ZO‐1 and Na+/K+‐ATPase. During the in vitro surgery, hCEC‐HALC constructs behaved most similar to the DMEK reference model during implantation and unfolding in the artificial AC, showing good adhesion to the bare stroma. On the other hand, hCEC‐LK20 and hCEC‐dDM constructs required some additional handling because of challenges related to the surgical procedure, although they were both successfully unfolded and implanted in the artificial AC. The hCEC‐dDM constructs showed similar graft adherence as hCEC‐HALC constructs, while adherence of hCEC‐LK20 constructs was less effective.ConclusionsAll analyzed carriers were suitable substrates for cultivating hCEC. During in vitro DMEK surgery, hCEC‐HALC constructs behaved most similar to a standard DMEK‐graft, while graft adhesion and surgical handling, respectively, are parameters still requiring optimization for hCEC‐LK20 and hCEC‐dDM constructs.

Mineral deposition and vascular invasion of hydroxyapatite reinforced collagen scaffolds seeded with human adipose-derived stem cells

BackgroundCollagen-based scaffolds reinforced with hydroxyapatite (HA) are an attractive choice for bone tissue engineering because their composition mimics that of bone. We previously reported the development of compression-molded collagen-HA scaffolds that exhibited high porosity, interconnected pores, and mechanical properties that were well-suited for surgical handling and fixation. The objective of this study was to investigate these novel collagen-HA scaffolds in combination with human adipose-derived stem cells (hASCs) as a template for bone formation in a subcutaneous athymic mouse model.MethodsCollagen-HA scaffolds and collagen-only scaffolds were fabricated as previously described, and a clinically approved bone void filler was used as a control for the material. Constructs were seeded with hASCs and were pre-treated with either control or osteogenic media. A cell-free group was also included. Scaffolds were implanted subcutaneously in the backs of athymic nude mice for 8 weeks. Mineral deposition was quantified via micro-computed tomography. Histological and immunofluorescence images of the explants were used to analyze their vascular invasion, remodeling and cellularity.ResultsCell-free collagen-HA scaffolds and those that were pre-seeded with osteogenically differentiated hASCs supported mineral deposition and vascular invasion at comparable rates, while cell-seeded constructs treated with the control medium showed lower mineralization after implantation. HA-reinforcement allowed collagen constructs to maintain their shape, provided improved cell-tissue-scaffold integration, and resulted in a more organized tissue when pre-treated in an osteogenic medium. Scaffold type and pre-treatment also determined osteoclast activity and therefore potential remodeling of the constructs.ConclusionsThe results of this study cumulatively indicate that treatment medium and scaffold composition direct mineralization and angiogenic tissue formation in an ectopic model. The data suggest that it may be necessary to match the scaffold with a particular cell type and cell-specific pre-treatment to achieve optimal bone formation.

Microstructured thin-film electrode technology enables proof of concept of scalable, soft auditory brainstem implants.

Auditory brainstem implants (ABIs) provide sound awareness to deaf individuals who are not candidates for the cochlear implant. The ABI electrode array rests on the surface of the cochlear nucleus (CN) in the brainstem and delivers multichannel electrical stimulation. The complex anatomy and physiology of the CN, together with poor spatial selectivity of electrical stimulation and inherent stiffness of contemporary multichannel arrays, leads to only modest auditory outcomes among ABI users. Here, we hypothesized that a soft ABI could enhance biomechanical compatibility with the curved CN surface. We developed implantable ABIs that are compatible with surgical handling, conform to the curvature of the CN after placement, and deliver efficient electrical stimulation. The soft ABI array design relies on precise microstructuring of plastic-metal-plastic multilayers to enable mechanical compliance, patterning, and electrical function. We fabricated soft ABIs to the scale of mouse and human CN and validated them in vitro. Experiments in mice demonstrated that these implants reliably evoked auditory neural activity over 1 month in vivo. Evaluation in human cadaveric models confirmed compatibility after insertion using an endoscopic-assisted craniotomy surgery, ease of array positioning, and robustness and reliability of the soft electrodes. This neurotechnology offers an opportunity to treat deafness in patients who are not candidates for the cochlear implant, and the design and manufacturing principles are broadly applicable to implantable soft bioelectronics throughout the central and peripheral nervous system.

In vivo comparison of a granular and putty form of a sintered and a non-sintered silica-enhanced hydroxyapatite bone substitute material.

Improved handling characteristics of bone substitute materials may facilitate surgical handling. However, the respective modifications should not alter the biological activity. For comparison of a granular and a putty form of two silica-enhanced bone substitute materials, in 30 rabbits, bilateral bone defects were created in the femoral condyle and randomly filled with (1) sintered, silica-enhanced (0.8 wt%) hydroxyapatite (ACg, n = 15); (2) ACg plus resorbable polymer (ACp, n = 15); (3) non-sintered silica-enhanced hydroxyapatite (hydroxyapatite/SiO2 ratio:61:39 wt%; NBg, n = 15); and (4) NBg plus matrix of resorbable polymer (NBp, n = 15). After 4, 8, and 12 weeks, respectively, new-formed bone, remaining bone substitute materials, and amount of soft tissue were quantified histomorphometrically. After four weeks, new-formed bone was increased for NBg/NBp in which NBp showed significantly less remaining bone substitute materials when compared to ACg. After two months, the highest amount of new-formed bone and the least remaining bone substitute materials were seen for NBg and NBp. ACp had less remaining bone substitute material when compared to ACg. In addition, amount of soft tissue was significantly enhanced in NBp when compared to ACg and NBg. After 12 weeks, NBp had significantly lower remaining bone substitute material when compared to ACg. Amount of soft tissue was significantly increased in NBp when compared to ACg and NBg. In accordance, based on an early increase of new-formed bone, a lower amount of remaining bone substitute material, and as well as a distinct degradation, superiority of the non-sintered bone substitute material to the sintered bone substitute material was seen. The effect of the resorbable polymer to each bone substitute material can be supposed to be rather marginal.