Initiating versus delaying treatment-dose anticoagulation in suspected venous thromboembolism (VTE) in post-operative hip and knee arthroplasty patients: Outcomes and risks.

Background: Hip and knee arthroplasty is a risk factor for venous thromboembolism (VTE). Initiation of treatment-dose anticoagulation in the post-operative period in suspected cases prior to confirmed diagnosis involves balancing increased bleeding risk to VTE-associated morbidity. Methods: A single-centre retrospective cohort study was undertaken comparing outcomes of empirical treatment of suspected VTE in post-operative elective lower-limb arthroplasty patients as opposed to delaying treatment until diagnosis is confirmed. All patients undergoing ultrasonography (US) or CT-pulmonary-angiogram (CTPA) for suspected VTE following elective total hip arthroplasty (THA) or total knee arthroplasty (TKA) between 05/05/17 and 19/07/21 were identified. Primary outcomes were surgical site infection (SSI), readmission, and other wound problems within 30-days of surgery. Results: 107 patients were included for analysis. 93 patients had suspected deep venous thrombosis (DVT), 21 had suspected pulmonary embolism (PE), and 7 were investigated for both DVT and PE. Empirical treatment-dose anticoagulation was initiated in 4 patients with suspected pulmonary embolism (PE) prior to CTPA, and 34 patients with suspected deep venous thrombosis (DVT) prior to US. No significant differences were noted in 30-day readmission rate ([DVT: 12 % vs 23 %, p = 0.41], [PE: 50 % vs 33 %, p = 1.00]), SSI rate ([DVT: 6 % vs 3 %, p = 1.00], [PE: 0 % vs 11 %, p = 1.00]) or other wound complication rate ([DVT: 3 % vs 3 %, p = 1.00), [PE 0 % vs 11 %, p = 1.00]) between empirically and non-empirically treated groups respectively. Conclusion: Empirical initiation of therapeutic anticoagulation in post-operative lower limb arthroplasty patients with suspected VTE appears to be safe practice prior to a definitive diagnosis.

A systematic review demonstrating correlation of MRI compositional parameters with clinical outcomes following articular cartilage repair interventions in the knee.

Objective: Compositional-MRI parameters enable the assessment of cartilage ultrastructure. Correlation of these parameters with clinical outcomes is unclear. This systematic review investigated the correlation of various compositional- MRI parameters with clinical outcome measures following cartilage repair or regeneration interventions in the knee. Design: This study was registered with PROSPERO and reported in accordance with PRISMA. PubMed, Institute of Science Index, Scopus, Cochrane Central Register of Controlled Trials, and Embase databases were searched. All studies, regardless of type, that presented correlation of compositional- MRI parameters with clinical outcome measures were included. Two researchers independently performed data extraction and QUADAS-2 analysis. Compositional-MRI parameter change following intervention and correlation with clinical outcome measures were evaluated. Results: 19 studies were included. Risk of bias was generally low. 5 different compositional parameters were observed from the included studies. However, due to the significant variability in the reporting of compositional-MRI parameters across studies, meta-analyses were possible only for T2 values and T2 index values (T2 value of repair cartilage relative to normal cartilage). Correlation of T2 values of repair cartilage with clinical outcome score was r â€‹= â€‹0.33 [0.15, 0.52]. Correlation of T2 index with clinical outcome score was r â€‹= â€‹0.52 [0.32, 0.77]. Conclusions: Correlation between T2 values and clinical outcome scores following knee cartilage repair were found. The heterogeneity of the correlations extracted from the included studies limited the scope for the meta-analysis. Thus, standardised, high-quality studies are required for better assessment of correlation between compositional MRI parameters and clinical outcome measures after cartilage repair. Registration number: PROSPERO CRD42021287364.Study protocol available on PROSPERO website.

Women's experiences of specialist perinatal mental health services: a qualitative evidence synthesis.

PURPOSE: Specialist perinatal mental health services identify and treat women experiencing mental health conditions during pregnancy and up to one year post birth. There is limited knowledge about women's experiences of care from specialist services. Evaluation and optimisation of service delivery requires knowledge of women's care experiences. This review aimed to systematically identify, appraise, and synthesise qualitative evidence exploring women's experiences of specialist perinatal mental health services. METHODS: A systematic literature search of five databases: Medline (OVID), EMBASE (Elsevier), PsycINFO (EBSCO), CINAHL (EBSCO) and Scopus (Elsevier), grey literature searching, and backward citation, identified a total of 1035 papers of which sixteen met inclusion criteria. Methodological quality of the included studies was assessed using the Critical Appraisal Skills Program (CASP) tool. RESULTS: Thematic synthesis identified three themes: connected relationships; new beginnings; and meaningful service delivery. Findings identified that relationships developed with clinicians were significant to women and their experience of care. Women valued continuity of care from dedicated non-judgemental clinicians. Peer support from other mothers was perceived as meaningful to women. Through service interventions women gained new insights into their infant's needs and grew in confidence as a mother. CONCLUSIONS: Women require provision of flexible and accessible specialist services with clinicians who are sensitive to their individual psychosocial needs and preferences. Examining discharge practices and continuing care needs is essential to ensure the best outcomes for women and their families.

The role of Platelet-Rich Plasma (PRP) intraarticular injections in restoring articular cartilage of osteoarthritic knees. A systematic review and meta-analysis.

Objective: To assess the effect of PRP on knee articular cartilage content (thickness/volume) and examine the correlation between cartilage changes and clinical outcomes in patients with knee OA. Method: A systematic literature search was performed using the Cochrane methodology in four online databases. Studies were included if they reported on cartilage content with cross-sectional imaging pre- and post-injection. A random-effects model meta-analysis was performed. Correlation with clinical outcomes was evaluated. Results: 14 studies (n â€‹= â€‹1099 patients) from 1452 records met the inclusion criteria: seven RCTs (n â€‹= â€‹688), one prospective (n â€‹= â€‹50), one retrospective (n â€‹= â€‹68), and four case-series (n â€‹= â€‹224). The PRP preparation process and treatment protocol varied widely (follow-up 6-12 months). In meta-analysis, PRP treatment was not associated with a significant increase in cartilage thickness (4 studies, n â€‹= â€‹187, standardized mean difference: Hedges g: 0.079; 95%CI: 0.358 - 0.516; p â€‹= â€‹0.723). Meta-analysis of 3 RCTs (n â€‹= â€‹112) showed no significant difference in the change of overall knee cartilage content with PRP injections compared with no PRP (Hedges' g: 0.217; 95%CI: 0.177 - 0.611; P â€‹= â€‹0.281). Conclusion: The current literature does not support the PRP as chondrogenic in treatment of knee OA. However, there is substantial heterogeneity in the evaluated studies which limits the robustness of any conclusion. An adequately powered RCT, with a standardized PRP regime and standardized high-resolution MRI is needed to definitely define any effect of PRP on knee cartilage content and its relation to clinical outcomes. Until such high-quality evidence becomes available, we recommend that PRP is not administered with the intention of promoting chondrogenesis.

The Paternal Experience of Fear of Childbirth: An Integrative Review.

BACKGROUND: It is estimated that approximately 13% of expectant fathers experience a pathological and debilitating fear of childbirth. OBJECTIVE: The aim of this integrative review was to examine and synthesise the current body of research relating to paternal experience of fear of childbirth. METHODS: A systematic literature search of five databases-CINAHL, Cochrane Library, MEDLINE, PsycArticles and PsycInfo-identified seventeen papers. Methodological quality of studies was assessed using the Crowe Critical Appraisal Tool. RESULTS: Thematic data analysis identified three themes: the focus of fathers' childbirth-related fears, the impact of fear of childbirth on health and wellbeing, and fear of childbirth as a private burden. DISCUSSION: Fear of childbirth is a significant and distressing experience for expectant fathers who may benefit from an opportunity to express their childbirth-related fears in an environment where they feel validated and supported. Antenatal education is recommended to enhance fathers' childbirth-related self-efficacy to reduce fear of childbirth. CONCLUSIONS: Fear of childbirth may negatively impact the lives of men and consequently their families. Further investigation into methods and models for identifying and supporting men at risk of or experiencing fear of childbirth is required to improve outcomes for this population of men.

Evaluating Interaction of Cord Blood Hematopoietic Stem/Progenitor Cells with Functionally Integrated Three-Dimensional Microenvironments.

Despite advances in ex vivo expansion of cord blood-derived hematopoietic stem/progenitor cells (CB-HSPC), challenges still remain regarding the ability to obtain, from a single unit, sufficient numbers of cells to treat an adolescent or adult patient. We and others have shown that CB-HSPC can be expanded ex vivo in two-dimensional (2D) cultures, but the absolute percentage of the more primitive stem cells decreases with time. During development, the fetal liver is the main site of HSPC expansion. Therefore, here we investigated, in vitro, the outcome of interactions of primitive HSPC with surrogate fetal liver environments. We compared bioengineered liver constructs made from a natural three-dimensional-liver-extracellular-matrix (3D-ECM) seeded with hepatoblasts, fetal liver-derived (LvSt), or bone marrow-derived stromal cells, to their respective 2D culture counterparts. We showed that the inclusion of cellular components within the 3D-ECM scaffolds was necessary for maintenance of HSPC viability in culture, and that irrespective of the microenvironment used, the 3D-ECM structures led to the maintenance of a more primitive subpopulation of HSPC, as determined by flow cytometry and colony forming assays. In addition, we showed that the timing and extent of expansion depends upon the biological component used, with LvSt providing the optimal balance between preservation of primitive CB HSPC and cellular differentiation. Stem Cells Translational Medicine 2018;7:271-282.

Self-assembled liver organoids recapitulate hepatobiliary organogenesis in vitro.

Several three-dimensional cell culture systems are currently available to create liver organoids. In gneral, these systems display better physiologic and metabolic aspects of intact liver tissue compared with two-dimensional culture systems. However, none reliably mimic human liver development, including parallel formation of hepatocyte and cholangiocyte anatomical structures. Here, we show that human fetal liver progenitor cells self-assembled inside acellular liver extracellular matrix scaffolds to form three-dimensional liver organoids that recapitulated several aspects of hepatobiliary organogenesis and resulted in concomitant formation of progressively more differentiated hepatocytes and bile duct structures. The duct morphogenesis process was interrupted by inhibiting Notch signaling, in an attempt to create a liver developmental disease model with a similar phenotype to Alagille syndrome. Conclusion: In the current study, we created an in vitro model of human liver development and disease, physiology, and metabolism, supported by liver extracellular matrix substrata; we envision that it will be used in the future to study mechanisms of hepatic and biliary development and for disease modeling and drug screening. (Hepatology 2018;67:750-761).

Shear stress upregulates regeneration-related immediate early genes in liver progenitors in 3D ECM-like microenvironments.

The role of fluid stresses in activating the hepatic stem/progenitor cell regenerative response is not well understood. This study hypothesized that immediate early genes (IEGs) with known links to liver regeneration will be upregulated in liver progenitor cells (LPCs) exposed to in vitro shear stresses on the order of those produced from elevated interstitial flow after partial hepatectomy. The objectives were: (1) to develop a shear flow chamber for application of fluid stress to LPCs in 3D culture; and (2) to determine the effects of fluid stress on IEG expression in LPCs. Two hours of shear stress exposure at ∼4 dyn/cm2 was applied to LPCs embedded individually or as 3D spheroids within a hyaluronic acid/collagen I hydrogel. Results were compared against static controls. Quantitative reverse transcriptase polymerase chain reaction was used to evaluate the effect of experimental treatments on gene expression. Twenty-nine genes were analyzed, including IEGs and other genes linked to liver regeneration. Four IEGs (CFOS, IP10, MKP1, ALB) and three other regeneration-related genes (WNT, VEGF, EpCAM) were significantly upregulated in LPCs in response to fluid mechanical stress. LPCs maintained an early to intermediate stage of differentiation in spheroid culture in the absence of the hydrogel, and addition of the gel initiated cholangiocyte differentiation programs which were abrogated by the onset of flow. Collectively the flow-upregulated genes fit the pattern of an LPC-mediated proliferative/regenerative response. These results suggest that fluid stresses are potentially important regulators of the LPC-mediated regeneration response in liver.

Sembragiline in Moderate Alzheimer's Disease: Results of a Randomized, Double-Blind, Placebo-Controlled Phase II Trial (MAyflOwer RoAD).

BACKGROUND: Sembragiline is a potent, selective, long-acting, and reversible MAO-B inhibitor developed as a potential treatment for Alzheimer's disease (AD). OBJECTIVE: To evaluate the safety, tolerability, and efficacy of sembragiline in patients with moderate AD. METHODS: In this Phase II study (NCT01677754), 542 patients with moderate dementia (MMSE 13-20) on background acetylcholinesterase inhibitors with/without memantine were randomized (1:1:1) to sembragiline 1 mg, 5 mg, or placebo once daily orally for 52 weeks. RESULTS: No differences between treated groups and placebo in adverse events or in study completion. The primary endpoint, change from baseline in ADAS-Cog11, was not met. At Week 52, the difference between sembragiline and placebo in ADAS-Cog11 change from baseline was - 0.15 (p = 0.865) and 0.90 (p = 0.312) for 1 and 5 mg groups, respectively. Relative to placebo at Week 52 (but not at prior assessment times), the 1 mg and 5 mg sembragiline groups showed differences in ADCS-ADL of 2.64 (p = 0.051) and 1.89 (p = 0.160), respectively. A treatment effect in neuropsychiatric symptoms (as assessed by the difference between sembragiline and placebo on BEHAVE-AD-FW) was also seen at Week 52 only: - 2.80 (p = 0.014; 1 mg) and - 2.64 (p = 0.019; 5 mg), respectively. A post hoc subgroup analysis revealed greater treatment effects on behavior and functioning in patients with more severe baseline behavioral symptoms (above the median). CONCLUSIONS: This study showed that sembragiline was well-tolerated in patients with moderate AD. The study missed its primary and secondary endpoints. Post hoc analyses suggested potential effect on neuropsychiatric symptoms and functioning in more behaviorally impaired study population at baseline.

Fluid Flow Regulation of Revascularization and Cellular Organization in a Bioengineered Liver Platform.

OBJECTIVE: Modeling of human liver development, especially cellular organization and the mechanisms underlying it, is fundamental for studying liver organogenesis and congenital diseases, yet there are no reliable models that mimic these processes ex vivo. DESIGN: Using an organ engineering approach and relevant cell lines, we designed a perfusion system that delivers discrete mechanical forces inside an acellular liver extracellular matrix scaffold to study the effects of mechanical stimulation in hepatic tissue organization. RESULTS: We observed a fluid flow rate-dependent response in cell distribution within the liver scaffold. Next, we determined the role of nitric oxide (NO) as a mediator of fluid flow effects on endothelial cells. We observed impairment of both neovascularization and liver tissue organization in the presence of selective inhibition of endothelial NO synthase. Similar results were observed in bioengineered livers grown under static conditions. CONCLUSION: Overall, we were able to unveil the potential central role of discrete mechanical stimulation through the NO pathway in the revascularization and cellular organization of a bioengineered liver. Last, we propose that this organ bioengineering platform can contribute significantly to the identification of physiological mechanisms of liver organogenesis and regeneration and improve our ability to bioengineer livers for transplantation.

Multiscale computational model of fluid flow and matrix deformation in decellularized liver.

Currently little is known about the biomechanical environment in decellularized tissue. The goal of this research is to quantify the mechanical microenvironment in decellularized liver, for varying organ-scale perfusion conditions, using a combined experimental/computational approach. Needle-guided ultra-miniature pressure sensors were inserted into liver tissue to measure parenchymal fluid pressure ex-situ in portal vein-perfused native (n=5) and decellularized (n=7) ferret liver, for flow rates from 3-12mL/min. Pressures were also recorded at the inlet near the portal vein cannula to estimate total vascular resistance of the specimens. Experimental results were fit to a multiscale computational model to simulate perfusion conditions inside native versus decellularized livers for four experimental flow rates. The multiscale model consists of two parts: an organ-scale electrical analog model of liver hemodynamics and a tissue-scale model that predicts pore fluid pressure, pore fluid velocity, and solid matrix stress and deformation throughout the 3D hepatic lobule. Distinct models were created for native versus decellularized liver. Results show that vascular resistance decreases by 82% as a result of decellularization. The hydraulic conductivity of the decellularized liver lobule, a measure of tissue permeability, was 5.6 times that of native liver. For the four flow rates studied, mean fluid pressures in the decellularized lobule were 0.6-2.4mmHg, mean fluid velocities were 211-767µm/s, and average solid matrix principal strains were 1.7-6.1%. In the future this modeling platform can be used to guide the optimization of perfusion seeding and conditioning strategies for decellularized scaffolds in liver bioengineering.

Rethinking niche evolution: experiments with natural communities of Protozoa in pitcher plants.

Classic niche theory predicts that competing species will evolve to use different resources and interact less, whereas recent niche-converge ideas predict that species evolve to use similar resources and interact more. Most data supporting niche evolution are based on observations of contemporary niche use, whereas experimental support is quite sparse. We followed the evolution of four species of Protozoa during succession in the water-filled leaves of the pitcher plant, Sarracenia purpurea, and found that evolution in multispecies systems follows a surprising pattern. Over several hundred generations, weak competitors evolved to be stronger, while strong competitors evolved to become weaker, which does not conform to expectations of either niche divergence or convergence. Evolution in this system appears to occur in response to characteristics of a suite of several competitors in the community, rather than pairwise interactions. Ecologists may need to rethink the roles of competition and evolution in structuring communities.

Whole-organ bioengineering: current tales of modern alchemy.

End-stage organ disease affects millions of people around the world, to whom organ transplantation is the only definitive cure available. However, persistent organ shortage and the resulting widespread transplant backlog are part of a disturbing reality and a common burden felt by thousands of patients on waiting lists in almost every country where organ transplants are performed. Several alternatives and potential solutions to this problem have been sought in past decades, but one seems particularly promising now: whole-organ bioengineering. This review describes briefly the evolution of organ transplantation and the development of decellularized organ scaffolds and their application to organ bioengineering. This modern alchemy of generating whole-organ scaffolds and recellularizing them with multiple cell types in perfusion bioreactors is paving the way for a new revolution in transplantation medicine. Furthermore, although the first generation of bioengineered organs still lacks true clinical value, it has created a number of novel tissue and organ model platforms with direct application in other areas of science (eg, developmental biology and stem cell biology, drug discovery, physiology and metabolism). In this review, we describe the current status and numerous applications of whole-organ bioengineering, focusing also on the multiple challenges that researchers have to overcome to translate these novel technologies fully into transplantation medicine.

Discarded human kidneys as a source of ECM scaffold for kidney regeneration technologies.

In the United States, more than 2600 kidneys are discarded annually, from the total number of kidneys procured for transplant. We hypothesized that this organ pool may be used as a platform for renal bioengineering and regeneration research. We previously showed that decellularization of porcine kidneys yields renal extracellular matrix (ECM) scaffolds that maintain their basic components, support cell growth and welfare in vitro and in vivo, and show an intact vasculature that, when such scaffolds are implanted in vivo, is able to sustain physiological blood pressure. The purpose of the current study was to test if the same strategy can be applied to discarded human kidneys in order to obtain human renal ECM scaffolds. The results show that the sodium dodecylsulfate-based decellularization protocol completely cleared the cellular compartment in these kidneys, while the innate ECM framework retained its architecture and biochemical properties. Samples of human renal ECM scaffolds stimulated angiogenesis in a chick chorioallantoic membrane assay. Importantly, the innate vascular network in the human renal ECM scaffolds retained its compliance. Collectively, these results indicate that discarded human kidneys are a suitable source of renal scaffolds and their use for tissue engineering applications may be more clinically applicable than kidneys derived from animals.

Human liver bioengineering using a whole liver decellularized bioscaffold.

As a result of significant progress made in the last years in developing methods of whole organ decellularization techniques, organ bioengineering may now look more feasible than ever before. In this chapter, we describe in detail the necessary steps in human liver bioengineering. These include ferret liver decellularization by detergent perfusion, human liver progenitor and endothelial cell isolation, and finally, liver bioscaffold recellularization in a perfusion bioreactor.

Scale-dependent mechanical properties of native and decellularized liver tissue.

Decellularization, a technique used in liver regenerative medicine, is the removal of all the cellular components from a tissue or organ, leaving behind an intact structure of extracellular matrix. The biomechanical properties of this novel scaffold material are currently unknown and are important due to the mechanosensitivity of liver cells. Characterizing this material is important for bioengineering liver tissue from this decellularized scaffold as well as creating new 3-dimensional mimetic structures of liver extracellular matrix. This study set out to characterize the biomechanical properties of perfused liver tissue in its native and decellularized states on both a macro- and nano-scale. Poroviscoelastic finite element models were then used to extract the fluid and solid mechanical properties from the experimental data. Tissue-level spherical indentation-relaxation tests were performed on 5 native livers and 8 decellularized livers at two indentation rates and at multiple perfusion rates. Cellular-level spherical nanoindentation was performed on 2 native livers and 1 decellularized liver. Tissue-level results found native liver tissue to possess a long-term Young's modulus of 10.5 kPa and decellularized tissue a modulus of 1.18 kPa. Cellular-level testing found native tissue to have a long-term Young's modulus of 4.40 kPa and decellularized tissue to have a modulus of 0.91 kPa. These results are important for regenerative medicine and tissue engineering where cellular response is dependent on the mechanical properties of the engineered scaffold.

Porohyperviscoelastic model simultaneously predicts parenchymal fluid pressure and reaction force in perfused liver.

Porohyperviscoelastic (PHVE) modeling gives a simplified continuum approximation of pore fluid behavior within the parenchyma of liver tissue. This modeling approach is particularly applicable to tissue engineering of artificial livers, where the inherent complexity of the engineered scaffolds prevents the use of computational fluid dynamics. The objectives of this study were to simultaneously predict the experimental parenchymal fluid pressure (PFP) and compression response in a PHVE liver model. The model PFP matched the experimental measurements (318 Pa) to within 1.5%. Linear regression of both phases of compression, ramp, and hold, demonstrated a strong correlation between the model and the experimental reaction force (p<0.5). The ability of this PVE model to accurately predict both fluid and solid behavior is important due to the highly vascularized nature of liver tissue and the mechanosensitivity of liver cells to solid matrix and fluid flow properties.

Evaluation of parenchymal fluid pressure in native and decellularized liver tissue.

One strategy for tissue engineering of bioartificial livers is the use of decellularized liver scaffolds, which contain a functional vascular network and intact extracellular matrix components. Due to the known mechanosensitivity of liver cells, particularly the response of hepatocytes to changes in parenchymal fluid pressure (PFP), it is necessary to evaluate the biomechanical environment within decellularized scaffolds. The objective of this study was to characterize the dependence of PFP on perfusion flow rate, in native and decellularized liver. Needle-guided Millar SPR-524 (3.5F) pressure sensors were inserted into liver parenchyma to measure PFP in-situ in rat (n=5) and ex-situ in portal vein-perfused native (n=5) and decellularized (n=7) liver tissue. Average in-situ PFP, measured in the left, central and right lobes, was found to be 2.86±1.04 mmHg. PFP measured in ex-situ liver perfused at 3, 6, 9, and 12 ml/min was found to increase linearly with flow rate. Decellularized liver PFP ranged from 0.68 mmHg at 3ml/min to 2.42 mmHg at 12 ml/min, while native liver ranged from 4.32 – 11.93 mmHg. Results demonstrate that PFP in decellularized scaffolds can be controlled by varying flow rate. These results will be implemented in a poroviscoelastic finite element model of liver perfusion, developed by the authors, to predict PFP distribution in three-dimensional scaffolds for known flow rates. This computationally efficient model can be used to optimize perfusion bioreactor conditions throughout the scaffold, to aid in the engineering of functional liver tissue from a decellularized liver organoid.

Production and implantation of renal extracellular matrix scaffolds from porcine kidneys as a platform for renal bioengineering investigations.

BACKGROUND: It is important to identify new sources of transplantable organs because of the critical shortage of donor organs. Tissue engineering holds the potential to address this issue through the implementation of decellularization-recellularization technology. OBJECTIVE: To produce and examine acellular renal extracellular matrix (ECM) scaffolds as a platform for kidney bioengineering. METHODS: Porcine kidneys were decellularized with distilled water and sodium dodecyl sulfate-based solution. After rinsing with buffer solution to remove the sodium dodecyl sulfate, the so-obtained renal ECM scaffolds were processed for vascular imaging, histology, and cell seeding to investigate the vascular patency, degree of decellularization, and scaffold biocompatibility in vitro. Four whole renal scaffolds were implanted in pigs to assess whether these constructs would sustain normal blood pressure and to determine their biocompatibility in vivo. Pigs were sacrificed after 2 weeks and the explanted scaffolds were processed for histology. RESULTS: Renal ECM scaffolds were successfully produced from porcine kidneys. Scaffolds retained their essential ECM architecture and an intact vascular tree and allowed cell growth. On implantation, unseeded scaffolds were easily reperfused, sustained blood pressure, and were tolerated throughout the study period. No blood extravasation occurred. Pathology of explanted scaffolds showed maintenance of renal ultrastructure. Presence of inflammatory cells in the pericapsular region and complete thrombosis of the vascular tree were evident. CONCLUSIONS: Our investigations show that pig kidneys can be successfully decellularized to produce renal ECM scaffolds. These scaffolds maintain their basic components, are biocompatible, and show intact, though thrombosed, vasculature.