Heterogeneity of Scaffold Biomaterials in Tissue Engineering.

Tissue engineering (TE) offers a potential solution for the shortage of transplantable organs and the need for novel methods of tissue repair. Methods of TE have advanced significantly in recent years, but there are challenges to using engineered tissues and organs including but not limited to: biocompatibility, immunogenicity, biodegradation, and toxicity. Analysis of biomaterials used as scaffolds may, however, elucidate how TE can be enhanced.

The efficacy and safety of mammalian target of rapamycin inhibitors ab initio after liver transplantation without corticosteroids or induction therapy.

Background: Mammalian target of rapamycin inhibitors have been used along with corticosteroids and/or induction therapy immediately after liver transplantation. Our aim was to assess the safety and tolerability of everolimus ab initio after liver transplantation without corticosteroids or induction, as well as efficacy in terms of liver function, rejection and graft loss.

Methods: A retrospective observational study of 50 adult patients (86% males, median age 54 years, range 25-68) who were liver transplanted between 2009 and 2013 and followed for 12 months.

The Human Pancreas as a Source of Protolerogenic Extracellular Matrix Scaffold for a New-generation Bioartificial Endocrine Pancreas.

Objectives: Our study aims at producing acellular extracellular matrix scaffolds from the human pancreas (hpaECMs) as a first critical step toward the production of a new-generation, fully human-derived bioartificial endocrine pancreas. In this bioartificial endocrine pancreas, the hardware will be represented by hpaECMs, whereas the software will consist in the cellular compartment generated from patient's own cells.

Background: Extracellular matrix (ECM)-based scaffolds obtained through the decellularization of native organs have become the favored platform in the field of complex organ bioengineering.

Kidney transplantation, bioengineering and regeneration: an originally immunology-based discipline destined to transition towards ad hoc organ manufacturing and repair.

Kidney transplantation (KT), as a modality of renal replacement therapy (RRT), has been shown to be both economically and functionally superior to dialysis for the treatment of end-stage renal disease (ESRD). Progress in KT is limited by two major barriers: a) a chronic and burgeoning shortage of transplantable organs and b) the need for chronic immunosuppression following transplantation. Although ground-breaking advances in transplant immunology have improved patient survival and graft durability, a new pathway of innovation is needed in order to overcome current obstacles.

Tissue-Engineering Approaches to Restore Kidney Function.

Kidney transplantation for the treatment of chronic kidney disease has established outcome and quality of life. However, its implementation is severely limited by a chronic shortage of donor organs; consequently, most candidates remain on dialysis and on the waiting list while accruing further morbidity and mortality. Furthermore, those patients that do receive kidney transplants are committed to a life-long regimen of immunosuppressive drugs that also carry significant adverse risk profiles.

Prospect for kidney bioengineering: shortcomings of the status quo.

Introduction: Dialysis and renal transplantation are the only two therapeutic options offered to patients affected by end-stage kidney disease; however, neither treatment can be considered definitive. In fact, dialysis is able to replace only the filtration function of the kidney without substituting its endocrine and metabolic roles, and dramatically impacts on patient's quality of life. On the other hand, kidney transplantation is severely limited by the shortage of transplantable organs, the need for immunosuppressive therapies and a narrow half-life.

Tissue engineering and regenerative medicine: semantic considerations for an evolving paradigm.

Tissue engineering (TE) and regenerative medicine (RM) are rapidly evolving fields that are often obscured by a dense cloud of hype and commercialization potential. We find, in the literature and general commentary, that several of the associated terms are casually referenced in varying contexts that ultimately result in the blurring of the distinguishing boundaries which define them. "TE" and "RM" are often used interchangeably, though some experts vehemently argue that they, in fact, represent different conceptual entities.

Biocompatibility and characterization of a peptide amphiphile hydrogel for applications in peripheral nerve regeneration.

Peripheral nerve injury is a debilitating condition for which new bioengineering solutions are needed. Autografting, the gold standard in treatment, involves sacrifice of a healthy nerve and results in loss of sensation or function at the donor site. One alternative solution to autografting is to use a nerve guide conduit designed to physically guide the nerve as it regenerates across the injury gap.

One-shot versus multidose perioperative antibiotic prophylaxis after kidney transplantation: a randomized, controlled clinical trial.

Background: There is no consensus on the optimal perioperative antibiotic prophylaxis regimen for renal transplant recipients. Some studies have reported that irrigation of the wound at the time of closure without systemic antibiotics may suffice to minimize the risk for surgical site infection (SSI), but many centers still use long-term, multidose regimens in which antibiotics are administered until removal of foreign bodies occur, such as the urethral catheter, drain and central line.

Methods: We designed a prospective, randomized, multicenter, controlled trial to compare a single dose versus a multidose regimen of systemic antibiotic prophylaxis in adult, nondiabetic, non-morbidly obese patients undergoing renal transplantation.

Abdominal organ bioengineering: current status and future perspectives.

Organ transplantation represents one of the major milestones of modern medicine and surgical practice in terms of life-years prolonged and quality of life offered for chronic patients. Each year over 100,000 donor organ transplants are performed worldwide. In spite of the rapid advancement and expansion of this niche, it has become a victim of its own success as the donor supply is far oustripped by the demand for replacement organs.

Osseus metaplasia in kidney allografts as a paradigm of regenerative medicine principles.

We report the sixth case of osseous metaplasia that has occurred in the last 5 years, after a deceased-donor renal transplant was performed on a young man. While its clinical significance is unclear and probably irrelevant, osseous metaplasia is one of the most relevant principles of regenerative medicine, where every bodily district contains progenitor cells that can generate cells specific to the germ layer from which they come. After the Case Report, we review the literature and speculate on the underlying pathophysiology of osseous metaplasia.

Semi-xenotransplantation: the regenerative medicine-based approach to immunosuppression-free transplantation and to meet the organ demand.

Although xenografts have always held immeasurable potential as an inexhaustible source of donor organs, immunological barriers and physiological incompatibility have proved to be formidable obstacles to clinical utility. An exciting, new regenerative medicine-based approach termed "semi-xenotransplantation" (SX) seeks to overcome these obstacles by combining the availability and reproducibility of animal organs with the biocompatibility and functionality of human allografts. Compared to conventional xenotransplantation wherein the whole organ is animal-derived, SX grafts are cleansed of their antigenic cellular compartment to produce whole-organ extracellular matrix scaffolds that retain their innate structure and vascular channels.

Extracellular Matrix Scaffold Technology for Bioartificial Pancreas Engineering: State of the Art and Future Challenges.

Emergent technologies in regenerative medicine may soon overcome the limitations of conventional diabetes therapies. Collaborative efforts across the subfields of stem cell technology, islet encapsulation, and biomaterial carriers seek to produce a bioengineered pancreas capable of restoring endocrine function in patients with insulin-dependent diabetes. These technologies rely on a robust understanding of the extracellular matrix (ECM), the supportive 3-dimensional network of proteins necessary for cellular attachment, proliferation, and differentiation.

Renal bioengineering with scaffolds generated from human kidneys.

Background: In 2012, about 16,487 people received kidney transplants in the USA whereas 95,022 candidates were on the waiting list at the end of the year. Moreover, more than 2,600 kidneys procured annually for transplantation are discarded for a variety of reasons. We hypothesize that this pool of discarded kidneys could in part meet the growing, urgent need for transplantable kidneys using current methods for organ bioengineering and regeneration and surgical transplantation.

Regeneration and bioengineering of the kidney: current status and future challenges.

The prevalence of chronic kidney disease continues to outpace the development of effective treatment strategies. For patients with advanced disease, renal replacement therapies approximate the filtration functions of the kidney at considerable cost and inconvenience, while failing to restore the resorptive and endocrine functions. Allogeneic transplantation remains the only restorative treatment, but donor shortage, surgical morbidity and the need for lifelong immunosuppression significantly limit clinical application.

2,4(5)-diarylimidazoles as inhibitors of hNaV1.2 sodium channels: pharmacological evaluation and structure-property relationships.

Sodium (Na) channels continue to represent an important target for the development of novel anticonvulsants. We have synthesized and evaluated a series of 2,4(5)-diarylimidazoles for inhibition of the human neuronal Na(V)1.2 Na channel isoform.

Development of probes for differentiation of infectious bursal disease virus strains of various virulence by dot-blot hybridization.

Two different radio-labeled nucleic acid probes, prepared from reverse transcription-polymerase chain reaction (RT-PCR) amplified variable region of VP2 and VP1 gene sequences of a highly virulent infectious bursal disease virus (IBDV), were tested for their ability to detect field isolates of IBDV directly in clinical bursal tissue specimens and vaccine strains of IBDV in tissue cultures. The VP2 gene probe was able to detect both field isolates and vaccine strains of IBDV under high as well as low stringency while the VP1 gene probe could differentiate under high stringency field isolates from vaccine strains, hybridizing only with RNA of field isolates. The sensitivity of both the probes was found to be 4 ng of purified viral RNA.

Characterization of the shed form of the human tumor-associated glycoprotein (TAG-72) from serous effusions of patients with different types of carcinomas.

Monoclonal antibody (MAb) B72.3 binds a high molecular weight tumor-associated glycoprotein designated TAG-72. This study reports the isolation and characterization of secreted TAG-72 directly from effusions of ovarian, colorectal, pancreatic, and endometrial carcinoma patients and compares them to TAG-72 derived from the LS-174T colon carcinoma xenograft.

Cooperation between fibronectin and heparin in the mobilization of capillary endothelium.

Angiogenesis is indispensable to sustain promotion and growth of metastases. As a contribution to the understanding of the angiogenesis process, the experiments reported showed that: (a) fibronectin is involved in the mobilization of capillary endothelium which is the first event in angiogenesis; (b) antifibronectin serum can block the mobilization, and neutralization of the antiserum can restore it; (c) the combination of fibronectin + heparin is a powerful mobilizer of capillary endothelium, and (d) fragments of the fibronectin and heparin molecules in combination can mobilize capillary endothelium as effectively as the intact molecules. The results are interpreted to indicate that molecules normally present in the extracellular matrix like heparin and fibronectin, may act as angiogenesis effectors when the physiological structure of the tissue is altered, for instance by lytic enzymes released by metastatic neoplastic cells.