Multichannel Conduits with Fascicular Complementation: Significance in Long Segmental Peripheral Nerve Injury.

Despite the advances in tissue engineering approaches, reconstruction of long segmental peripheral nerve defects remains unsatisfactory. Although autologous grafts with proper fascicular complementation have shown meaningful functional recovery according to the Medical Research Council Classification (MRCC), the lack of donor nerve for such larger defect sizes (>30 mm) has been a serious clinical issue. Further clinical use of hollow nerve conduits is limited to bridging smaller segmental defects of denuded nerve ends (<30 mm). Recently, bioinspired multichannel nerve guidance conduits (NGCs) gained attention as autograft substitutes as they mimic the fascicular connective tissue microarchitecture in promoting aligned axonal outgrowth with desirable innervation for complete sensory and motor function restoration. This review outlines the hierarchical organization of nerve bundles and their significance in the sensory and motor functions of peripheral nerves. This review also emphasizes the major challenges in addressing the longer nerve defects with the role of fascicular arrangement in the multichannel nerve guidance conduits and the need for fascicular matching to accomplish complete functional restoration, especially in treating long segmental nerve defects. Further, currently available fabrication strategies in developing multichannel nerve conduits and their inconsistency in existing preclinical outcomes captured in this review would seed a new process in designing an ideal larger nerve conduit for peripheral nerve repair.

Continuous Low-Intensity Ultrasound Improves Cartilage Repair in Rabbit Model of Subchondral Injury.

Subchondral drilling (SD), a bone marrow stimulation technique, is used to repair cartilage lesions that lack regenerative potential. Cartilage repair outcomes upon SD are typically fibrocartilaginous in nature with inferior functionality. The lack of cues to foster the chondrogenic differentiation of egressed mesenchymal stromal cells upon SD can be attributed for the poor outcomes. Continuous low-intensity ultrasound (cLIUS) at 3.8 MHz is proposed as a treatment modality for improving cartilage repair outcomes upon marrow stimulation. Bilateral defects were created by SD on the femoral medial condyle of female New Zealand white rabbits (n = 12), and the left joint received cLIUS treatment (3.8 MHz, 3.5 Vpp, 8 min/application/day) and the contralateral right joint served as the control. On day 7 postsurgery, synovial fluid was aspirated, and the cytokine levels were assessed by Quantibody™ assay. Rabbits were euthanized at 8 weeks and outcomes were assessed macroscopically and histologically. Defect areas in the right joints exhibited boundaries, incomplete fill, irregular cartilage surfaces, loss of glycosaminoglycan (GAG), and absence of chondrocytes. In contrast, the repaired defect area in the joints that received cLIUS showed complete fill, positive staining for GAG with rounded chondrocyte morphology, COL2A1 staining, and columnar organization. Synovial fluid collected from cLIUS-treated left knee joints had lower levels of IL1, TNFα, and IFNγ when compared to untreated right knee joints, alluding to the potential of cLIUS to mitigate early inflammation. Further at 8 weeks, left knee joints (n = 12) consistently scored higher on the O'Driscoll scale, with a higher percent hyaline cartilage score. No adverse impact on bone or change in the joint space was noted. Upon a single exposure of cLIUS to TNFα-treated cells, nuclear localization of pNFκB and SOX9 was visualized by double immunofluorescence and the expression of markers associated with the NFκB pathway was assayed by quantitative real-time polymerase chain reaction. cLIUS extends its chondroprotective effects by titrating pNFκB levels, preventing its nuclear translocation, while maintaining the expression of SOX9, the collagen II transcription factor. Our combined results demonstrate that healing of chondral defects treated with marrow stimulation by SD can be accelerated by employing cLIUS regimen that possesses chondroinductive and chondroprotective properties. Impact statement Repair of cartilage represents an unsolved biomedical burden. In vitro, continuous low-intensity ultrasound (cLIUS) has been demonstrated to possess chondroinductive and chondroprotective potential. To our best knowledge, the use of cLIUS to improve cartilage repair outcomes upon marrow stimulation, in vivo, has not been reported and our work reported here fills that gap. Our results demonstrated enhanced cartilage repair outcomes under cLIUS (3.8 MHz) in a rabbit model of subchondral injury by subchondral drilling. Enhanced repair stemmed from mesenchymal stem cell differentiation in vivo and the subsequent synthesis of articular cartilage-specific matrix.

Self-assembled multifunctional nanotheranostics against circulating tumor clusters in metastatic breast cancer.

Circulating tumor clusters (CTC) disseminating from the primary tumor are responsible for secondary tumor formation where the conventional treatments such as chemotherapy and radiotherapy does not prevent the metastasis at locally advanced stage of breast cancer. In this study, a smart nanotheranostic system has been developed to track and eliminate the CTCs before it can colonize at a new site, which would reduce metastatic progression and increase the five-year survival rate of the breast cancer patients. Targeted multiresponsive (magnetic hyperthermia and pH) nanomicelles incorporated with NIR fluorescent superparamagnetic iron oxide nanoparticles were developed based on self-assembly for dual modal imaging and dual toxicity for spontaneous killing of CTCs in blood stream. A heterogenous tumor clusters model was developed to mimic the CTCs isolated from breast cancer patients. The nanotheranostic system was further evaluated for the targeting property, drug release kinetics, hyperthermia and cytotoxicity against developed CTC model in vitro. In vivo model in BALB/c mice equivalent to stage III and IV human metastatic breast cancer was developed to evaluate the biodistribution and therapeutic efficacy of micellar nanotheranostic system. Reduced CTCs in blood stream and low distant organ metastasis after treatment with the nanotheranostic system demonstrates its potential to capture and kill the CTCs that minimize the secondary tumor formation at distant sites.

Facile fabrication of Bi-layered perfusable hydrogel tubes as biomimetic 3D arterial construct.

Small-diameter arterial conduits with native physiological and biological equivalence continues to be a constant global demand posing critical challenges in fabrication. Advent of various strategies towards mimicking the structural hierarchy of a native blood vessel, often involve complex instrumentation and template-assistance with post-processing complications eventually compromising structural fidelity. In the present research, we report a template-free, facile strategy- '3D wet writing' by peripheral-core differential ionic gelation to fabricate perfusable customizable constructs of any dimension, thickness and length in <5 mins. Dual-crosslinking using di-diol complexation of borax with Alginate- poly (vinyl alcohol) was performed to enhance the stability of fabricated bi-layered tubular constructs (BLT). These fabricated BLTs demonstrated non-linear mechanical characteristics of native blood vessels in withstanding physiological (120/80 mmHg) hemodynamic loading conditions with cyclic strain (5.82 ± 0.88%). The BLTs also ensured adequate longitudinal (0.176 ± 0.03 MPa) & circumferential (0.29 ± 0.012 MPa) tensile strength and burst pressure strength of 353.875 ± 22.69 mmHg. Hemocompatible characteristics of BLT were clearly evident with lower hemolytic index (0.21 ± 0.03%) and maintenance of erythrocyte structural integrity under dynamic conditions. Further, non-thrombogenic and non-inflammatory characteristics of BLTs were confirmed by in-activated platelets and monocytes under dynamic conditions. The developed wet-writing technique exhibited facile integration of layer-specific cells concurrently with the BLT fabrication. The spatial cell-specific expressions of smooth muscle (α-SMA) and endothelial (CD-31) cells in BLT were comparable to native hierarchical cellular organization with the multi-layered medial and mono-layered intimal layers. Further,ex-vivodynamic studies on anastomotic interface between BLT and rat abdominal aorta clearly evidenced the functional efficacy of fabricated BLTs as physiologically relevant small-diameter vascular construct.

Nanohydroxyapatite-Protein Interface in Composite Sintered Scaffold Influences Bone Regeneration in Rabbit Ulnar Segmental Defect.

The healing physiology of bone repair and remodeling that occurs after normal fracture is well orchestrated. However, it fails in complex clinical conditions and hence requires augmentation by grafts. In this study, composite nanohydroxyapatite (nHA), poly(hydroxybutyrate) (PHB) and poly(ɛ-caprolactone) (PCL) constituted microspheres sintered three-dimensional scaffold were evaluated in rabbit ulnar segmental defect. A composite scaffold using PHB-PCL-nHA microspheres was developed with protein interface by solvent/non-solvent sintering to provide multiple cues such as biocomposition, cancellous bone equivalent meso-micro multi-scale porosity, and compressive strength. In vitro DNA quantification and alkaline phosphatase (ALP) assays revealed that the protein interfaced composite scaffolds supported osteoblast proliferation and mineralization significantly higher than scaffolds without protein and TCPS (p < 0.05). Scanning electron micrographs of osteoblasts cultured scaffolds demonstrated cell-matrix interaction, cell spreading, colonization and filopodial extension across the porous voids. Cylindrical scaffolds (5 × 10 mm) were implanted following segmental defect (10 mm) in rabbit ulnar bone and compared with untreated control. Radiography (4, 8 and 12 weeks) and µ-computed tomography (12 weeks) analysis showed directional bone tissue formation by bridging defective site in both scaffolds with and without protein interface. Whereas, undesired sclerotic-like tissue formation was observed in control groups from 8 weeks. Histology by hot Stevenel's blue and van Gieson's picrofuchsin staining has confirmed enhanced bone maturation in scaffold groups while presence of osteoids was observed in control after 12 weeks. Thus, the developed composite matrices exhibits osteoinductive, osteoconductive properties and demonstrates its bone regenerative potential owing to its compositional, micro & macro structural and mechanical properties. Graphical abstract.

Continuous Low-Intensity Ultrasound Preserves Chondrogenesis of Mesenchymal Stromal Cells in the Presence of Cytokines by Inhibiting NFκB Activation.

Proinflammatory joint environment, coupled with impeded chondrogenic differentiation of mesenchymal stromal cells (MSCs), led to inferior cartilage repair outcomes. Nuclear translocation of phosphorylated-NFκB downregulates SOX9 and hinders the chondrogenesis of MSCs. Strategies that minimize the deleterious effects of NFκB, while promoting MSC chondrogenesis, are of interest. This study establishes the ability of continuous low-intensity ultrasound (cLIUS) to preserve MSC chondrogenesis in a proinflammatory environment. MSCs were seeded in alginate:collagen hydrogels and cultured for 21 days in an ultrasound-assisted bioreactor (5.0 MHz, 2.5 Vpp; 4 applications/day) in the presence of IL1ß and evaluated by qRT-PCR and immunofluorescence. The differential expression of markers associated with the NFκB pathway was assessed upon a single exposure of cLIUS and assayed by Western blotting, qRT-PCR, and immunofluorescence. Mitochondrial potential was evaluated by tetramethylrhodamine methyl ester (TMRM) assay. The chondroinductive potential of cLIUS was noted by the increased expression of SOX9 and COLII. cLIUS extended its chondroprotective effects by stabilizing the NFκB complex in the cytoplasm via engaging the IκBα feedback mechanism, thus preventing its nuclear translocation. cLIUS acted as a mitochondrial protective agent by restoring the mitochondrial potential and the mitochondrial mRNA expression in a proinflammatory environment. Altogether, our results demonstrated the potential of cLIUS for cartilage repair and regeneration under proinflammatory conditions.

Self-Standing Photo-Crosslinked Hydrogel Construct: in vitro Microphysiological Vascular Model.

Modeling of the human vascular microphysiological system (MPS) has gained attention due to precise prediction of drug response and toxicity during drug screening process. Developing a physiologically equivalent vascular MPS still remains complex as it demands the recapitulation of dynamic structural and biological microenvironment similar to native vasculature. Hence, an ideal MPS would involve developing perfusable 3D in vitro models with multilayered human vascular cells encapsulated in a matrix to regulate the vascular tone resembling the native. Several attempts to model such anatomically accurate physiological and pathological blood vessels often fail to harmonize the essential vascular microenvironment. For instance, conventional microfluidic-based approaches employed for vascular MPS, though offering creation of perfusable channel, do not replicate the vascular hierarchical cellular arrangement due to planar geometry and confluent monolayered cell seeding. Also, recent advances with 3D biofabrication strategies are still limited by fabrication of small-diameter constructs and scalability besides post-processing techniques that indirectly distort the structural integrity of the hydrogel tubular constructs. These existing limitations toward fabricating a relevant vascular MPS demand a facile and mechanically stable construct. Hence, the present study is aimed toward developing a stable viable self-standing perfusable hydrogel construct by a rapid and scalable strategy toward vascular MPS application. The fabricated tubular constructs were found to be structurally stable with end-to-end perfusability exhibiting their potential as self-standing perfusable structures. Also, the construct exhibited nonhemolytic behavior with perfusion of red blood cells inside the luminal channel. The present study evidences creation of a dual-crosslinked stable, viable self-standing hydrogel construct with multilayered homogenous distribution of viable smooth muscle cells throughout the construct, thereby demonstrating its applicability as a promising 3D in vitro vascular microphysiological system.

Ocular Manifestations in Patients of HIV(Human Immunodeficiency Virus) Infection on Combined Anti-Retroviral Therapy (CART).

AIM: To determine the prevalence and spectrum of ocular manifestations in PLHIV (people living with Human Immunodeficiency Virus) on cART (combined Antiretroviral Therapy) and correlate them with WHO clinical staging, CD4 count, duration & type of cART. METHODS: Observational cross-sectional study. Ophthalmic evaluation of 350 PLHIV on cART (at least 6 months) was done. Logistic regression was done to correlate ocular findings with different variables. Results: Prevalence of ocular, anterior & posterior segment manifestations was 15.71%, 10.86%, and 4.00%, respectively. Dry eye(8.00%) being the most common finding. PLHIV with CD4 count ≤350 (OR = 3.1,p < 0.001), in WHO stage 3 (OR = 26.9,p = 0.004) & 4(OR = 60.7,p < 0.001) & on 3rdlineART were at much higher risk of ocular manifestations as compared to those on 2nd (OR = 2.83) and 1stline (OR = 6.6) of therapy. Duration of treatment had a protective (p = 0.01) effect on bilateral manifestations. CONCLUSION: With early initiation of ART, there is significant reduction in the overall prevalence of ocular findings, in the number of opportunistic ophthalmic infections and blinding disorders. Of all the reported ocular findings, anterior segment disorder emerged more often.

Reverse engineering of an anatomically equivalent nerve conduit.

Reconstruction of peripheral nervous tissue remains challenging in critical-sized defects due to the lack of Büngner bands from the proximal to the distal nerve ends. Conventional nerve guides fail to bridge the large-sized defect owing to the formation of a thin fibrin cable. Hence, in the present study, an attempt was made to reverse engineer the intricate epi-, peri- and endo-neurial tissues using Fused Deposition Modeling based 3D printing. Bovine serum albumin protein nanoflowers (NF) exhibiting Viburnum opulus 'Roseum' morphology were ingrained into 3D printed constructs without affecting its secondary structure to enhance the axonal guidance from proximal to distal ends of denuded nerve ends. Scanning electron micrographs confirmed the uniform distribution of protein NF in 3D printed constructs. The PC-12 cells cultured on protein ingrained 3D printed scaffolds demonstrated cytocompatibility, improved cell adhesion and extended neuronal projections with significantly higher intensities of NF-200 and tubulin expressions. Further suture-free fixation designed in the current 3D printed construct aids facile implantation of printed conduits to the transected nerve ends. Hence the protein ingrained 3D printed construct would be a promising substitute to treat longer peripheral nerve defects as its structural equivalence of endo- and perineurial organization along with the ingrained protein NF promote the neuronal extension towards the distal ends by minimizing axonal dispersion.

Disease burden of diabetes, diabetic retinopathy and their future projections in the UK: cross-sectional analyses of a primary care database.

OBJECTIVES: To estimate the current disease burden, trends and future projections for diabetes mellitus (DM) and diabetic retinopathy (DR) in the IQVIA Medical Research Data (IMRD). PARTICIPANTS/DESIGN/SETTING: We performed a cross-sectional study of patients aged 12 and above to determine the prevalence of DM and DR from the IMRD database (primary care database) in January 2017, involving a total population of 1 80 824 patients with DM. We also carried out a series of cross-sectional studies to investigate prevalence trends, and then applied a double exponential smoothing model to forecast the future burden of DM and DR in the UK. RESULTS: The crude DM prevalence in 2017 was 5.2%. The DR, sight-threatening retinopathy (STR) and diabetic maculopathy prevalence figures in 2017 were 33.78%, 12.28% and 7.86%, respectively, in our IMRD cross-sectional study. There were upward trends in the prevalence of DM, DR and STR, most marked and accelerating in STR in type 1 DM but slowing in type 2 DM, and in the overall prevalence of DR. CONCLUSION: Our results suggest differential rising trends in the prevalence of DM and DR. Preventive strategies, as well as treatment services planning, can be based on these projected prevalence estimates. Improvements that are necessary for the optimisation of care pathways, and preparations to meet demand and capacity challenges, can also be based on this information. The limitations of the study can be overcome by a future collaborative study linking DR screening and hospital eye services data.

Tissue engineering approaches towards the regeneration of biomimetic scaffolds for age-related macular degeneration.

Age-related macular degeneration (AMD) is the third major cause of blindness in people aged above 60 years. It causes dysfunction of the retinal pigment epithelium (RPE) and leads to an irreversible loss of central vision. The present clinical treatment options are more palliative in controlling the progression of the disease and do not functionally restore the degenerated RPE monolayer and photoreceptors. Currently, the clinical transplantation of RPE cells has shown poor engraftment potential due to the absence of an intact Bruch's membrane in AMD patients, thereby the vision is unable to be restored completely. Although tissue engineering strategies target the development of Bruch's membrane-mimetic substrates, the challenge still lies in the development of an ultrathin, biologically and mechanically equivalent membrane to restore visual acuity. Further, existing limitations such as cellular aggregation, surgical complications including retinal tissue damage, tissue rejection, disease transmission, inferior mechanical strength, and the loss of vision over time demand the search for an ideal strategy to restore the functional RPE. Hence, this review aims to provide insights into various approaches, from conventional cell therapy to 3D bioprinting, and their unmet challenges in treating AMD by outlining the pathophysiology of AMD and the host tissue response with respect to injury, treatment and preclinical animal models.

Third Line Antiretroviral Treatment in India: Cohort Analysis and Treatment Outcomes from a Public Health Facility.

The National Programme in India provides free third-line antiretroviral treatment (ART) for all people living with HIV (PLHIV). Data of 232 PLHIV initiated on third-line ART from a single center in New Delhi were retrospectively analyzed for virological suppression at 6 and 12 months, factors predicting nonresponse, retention in care, and mortality from June 2016 till December 2019. The mean age at third-line ART initiation was 39.54 ± 11.08 years, 71.5% were males, and 55.02% had HIV duration of >10 years. The mean CD4 count at third-line ART initiation was 260.04 ± 200.4/mm3, and the median viral load (VL) at second-line failure was 61,253 copies/mL (interquartile range, 12,599-315,497 copies/mL). Of the patients, 71.52% achieved virological suppression at 6 months (n = 151), and this was maintained at 12 months-72% (n = 50). The mortality rate among those still in active care was 8.69% (18/207). PLHIV who did not attain virological suppression at 6 months had significantly shorter duration on second-line ART (p = 0.0002), lower peak CD4 achieved on second-line ART (p = 0.039), higher VL at second-line failure (p = 0.012), and lower body weight (p < 0.0001). On univariate analysis, lower CD4 peak on second-line ART (p = 0.019), lower CD4 count at third-line ART initiation (p = 0.004), and lower body weight (p = 0.0002) were significantly predictive of virological nonsuppression at 6 months. Successful implementation of a third-line ART program can indeed be done through a public health approach. Intensive adherence support, nutritional rehabilitation, and regular viral load monitoring are crucial for improved clinical and virological outcomes.

Recent advancements in cardiovascular bioprinting and bioprinted cardiac constructs.

Cardiovascular diseases (CVDs) are the leading causes of mortality globally that demand the application of tissue engineering strategies to repair damaged tissues. Conventional tissue engineering approaches such as particulate leaching, hydrogels, gas foaming, solvent casting and electrospinning based strategies aim to develop extracellular matrix analogues to promote the regeneration of functional cardiac tissues. However, poor cell seeding efficiency with the non-uniform distribution of cells across thicker scaffolds (>5 mm) limits the clinical potential. The advent of 3D bioprinting offers layer-by-layer cellular integration and facilitates the recapitulation of cellular heterogeneity and intricate hierarchical structural organization. Although the success of 3D bioprinting of cardiac specific tissues has been demonstrated in varying degrees, maintaining unique architecture, cellular heterogeneity and cardiac functions demands the search for cardiac-specific bioinks. Hence, this review outlines the various bioinks explored in the printing of cardiac tissues and the essential properties such as rheological and electromechanical characteristics necessary for the functional restoration. This review further describes the application of 3D bioprinting for the fabrication of several cardiac tissues such as heart valves, coronary arteries, cardiac patches and whole heart. Finally, this review summarizes the existing limitations, unmet technical challenges and potential future focus on the expansion of bioprinting technique to cardiovascular medicine.

Perceived social support, depression and their impact on quality of life of people living with HIV in India.

Universal access to Antiretroviral Treatment (ART) has transformed HIV/AIDS into a chronic disease and issues like social support and Quality of life (QOL) have emerged as important components of care. Perceived social support influences QOL in People Living with HIV (PLHIV), though this has not been studied well in India. PLHIV were assessed for Social Support using the Multidimensional Scale of Perceived Social Support (MSPSS) and QOL was assessed with the Medical Outcomes Study HIV Health Survey (MOS-HIV) questionnaire. The factors impacting social support and its effect of on QOL were analysed. Amongst the 109 study subjects, 62 (56.9%) were men, 47 (43.1%) were women, mean age was 35 ± 7.5 years, 85.3% had WHO stage 1 disease and 80 (73.4%) were receiving ART. Only 43.1% subjects perceived high overall social support. Social support (from family/friends/others) was associated positively with physical functioning (p = 0.001), social and cognitive functioning (p = 0.000) and significantly inversely associated with depression (p = 0.002). Higher perceived social support was seen to correlate with higher CD4 count (Peak, Nadir and Current; p < 0.05) and better adherence (p = 0.003). It is concluded that social support, including support from beyond family, have a significant impact on clinical endpoints and QOL in PLHIV.

Surface modified NIR magnetic nanoprobes for theranostic applications.

Objectives: Near-Infrared based imaging modalities integrated with thermotherapy can facilitate detection of cancer at early stages and mediate high-resolution image-guided hyperthermia. In this work, fluorescent iron oxide nanoparticles (FIO) have been developed possessing deep tissue penetrable NIR imaging and site-specific magnetic hyperthermia characteristics for the elimination of cancer cells.Methods: One-pot synthesis of amine-functionalized superparamagnetic iron oxide nanoparticles (HIO) were achieved using ethylenediamine (EDA) facilitated conjugation of indocyanine green (ICG) mediated by electrostatic interactions.Results: EDA acts as a capping and reducing agent to direct the structural growth of hydrophilic Fe3O4 nanocrystals with high saturation magnetization, specific absorption rate, and T2 value of 118 emu/g, 329.8 ± 5.96 W/g, and 40.17 mM-1s-1, respectively. Here, Fe2+/Fe3+ of two was maintained to achieve magnetite nanocrystals contradictory to the gold standard ratio of 0.5 without additives for nucleation and growth. Developed FIO showed excellent cytocompatibility even at higher concentrations and on subjecting to magnetic hyperthermia reduced its survival percentage. FIO biodistribution in mice showed enhanced half-life than free ICG with preferential localization in the brain and liver.Conclusion: Developed FIO using a facile technique is a potential clinical alternative for cellular tracking, imaging, and hyperthermia.

Marigold-like tyrosinase-embedded nanostructures-a nano-in-micro system.

Marigold-like tyrosinase-entrenched nanostructures were developed by a facile method using a metal cofactor to overcome the limitations of conventional enzyme immobilization techniques. The protein-copper complex promotes the hierarchical self-assembly of nanopetals into marigold-like microstructures through a sequential germination process. Nanopetals, which originated from bead-like tiny projections, showed budding over the surface and promoted the anisotropic growth of copper phosphate nanocrystals upon co-ordination with the active functional groups in protein. This organic-inorganic hybrid showed excellent re-usability, comparable catalytic efficiency, faster reaction rate, improved storage, and thermal stability without affecting the enzyme activity.

Outcomes and implications of a single brain death examination policy on organ donation outcomes at a high-volume trauma center.

BACKGROUND: Despite current neurological guidelines that a single brain death examination (SBDE) is sufficient to determine brain death, a vast majority of hospitals still use a two brain death examination (TBDE) policy based on historical practice. The purpose of this study was to analyze the outcomes and implications of an SBDE policy compared with a TBDE policy with respect to organ donation outcomes. METHODS: We retrospectively reviewed all adult patients declared dead by neurological criteria between 2010 and 2018 at a high-volume trauma center. The study population was divided into SBDE and TBDE cohorts. Primary outcomes included time to organ donation, terminal donor creatinine and bilirubin, and number of procured and transplanted organs. RESULTS: A total of 327 patients comprised the study population: 66.7% SBDE (n = 218 of 327 patients) and 33.3% TBDE (n = 109 of 327 patients). The SBDE group had a shorter median time from examination to procurement (38 vs. 44 hours, p = 0.02) as well as lower terminal donor creatinine (1.1 vs. 1.35 mg/dL, p = 0.004) and bilirubin (0.8 vs. 1.1 mg/dL, p = 0.04). Furthermore, the SBDE group had a significantly greater proportion of kidneys (90.6% vs. 81.6%, p = 0.02), lungs (11.8% vs. 4.6%, p = 0.02), and total organs (58.2% vs. 46.6%; p = 0.0001) procured with intent to transplant and a greater proportion of total organs transplanted (53.1% vs. 42.4%, p = 0.0004). Multivariable regression analysis confirmed that SBDE was independently associated with a shorter time to procurement, lower terminal creatinine, and increased number of procured organs. CONCLUSION: These data highlight the potential benefit of an SBDE policy with regards to organ donation outcomes at a high-volume trauma center and should facilitate future randomized prospective studies to more rigorously test this hypothesis. LEVEL OF EVIDENCE: Therapeutic/Care Management, level IV.

Bruch's membrane pathology: A mechanistic perspective.

Bruch's membrane, an extracellular matrix located between the retinal pigment epithelium and the choroid, plays a vital role as structural and functional support to the retinal pigment epithelium. Dysfunction of Bruch's membrane in both age-related macular degeneration and other ocular diseases is caused mostly by extracellular matrix degeneration, deposit formation, and angiogenesis. Although these factors are dealt in greater detail with respect to the cells that are degenerated such as the retinal pigment epithelium and the endothelial cells, the pathology involving the Bruch's membrane is often underrated. Since in most of the macular degenerations early degenerative changes are also observed in the Bruch's membrane, addressing only the cellular component without the underlying membrane will not yield an ideal clinical benefit. This review aims to discuss the factors and the mechanisms affecting the integrity of the Bruch's membrane, which would aid in developing an effective therapy for these pathologies.

Additive manufacturing of biodegradable porous orthopaedic screw.

Advent of additive manufacturing in biomedical field has nurtured fabrication of complex, customizable and reproducible orthopaedic implants. Layer-by-layer deposition of biodegradable polymer employed in development of porous orthopaedic screws promises gradual dissolution and complete metabolic resorption thereby overcoming the limitations of conventional metallic screws. In the present study, screws with different pore sizes (916 × 918 µm to 254 × 146 µm) were 3D printed at 200 µm layer height by varying printing parameters such as print speed, fill density and travel speed to augment the bone ingrowth. Micro-CT analysis and scanning electron micrographs of screws with 45% fill density confirmed porous interconnections (40.1%) and optimal pore size (259 × 207 × 200 µm) without compromising the mechanical strength (24.58 ± 1.36 MPa). Due to the open pore structure, the 3D printed screws showed increased weight gain due to the deposition of calcium when incubated in simulated body fluid. Osteoblast-like cells attached on screw and infiltrated into the pores over 14 days of in vitro culture. Further, the screws also supported greater human mesenchymal stem cell adhesion, proliferation and mineralized matrix synthesis over a period of 21 days in vitro culture as compared to non-porous screws. These porous screws showed significantly increased vascularization in a rat subcutaneous implantation as compared to control screws. Porous screws produced by additive manufacturing may promote better osteointegration due to enhanced mineralization and vascularization.

Clinical complications of biodegradable screws for ligament injuries.

Anterior cruciate ligament (ACL) plays a crucial role stabilizing the knee joint while connecting tibia to femur. Lack of proper treatment of injured ACL can lead to meniscus tear and osteoarthritis. Interference screws secure the graft tissue for superior integration of graft on host tissue during autograft fixation. Metal interference screws come with various disadvantages like mechanical load mismatch, graft laceration, secondary surgical removal and hindrance during MRI and CT post-operative scan. Though biodegradable polymeric screws provide various advantages their clinical outcomes reveal unprecedented complications for long term use of such screws. This review highlights polymer and composite screw currently available for surgical fixations and associated adverse reactions with the proposed mechanism for tunnel enlargement, effusion, osteolysis in ligament repairs. The need for suitable material engineering for development of orthopedic screws for successful rigid fixation has been highlighted in this review.