Regenerative Medicine and Diabetes: Targeting the Extracellular Matrix Beyond the Stem Cell Approach and Encapsulation Technology

According to the Juvenile Diabetes Research Foundation (JDRF), almost 1. 25 million people in the United States (US) have type 1 diabetes, which makes them dependent on insulin injections. Nationwide, type 2 diabetes rates have nearly doubled in the past 20 years resulting in more than 29 million American adults with diabetes and another 86 million in a pre-diabetic state. The International Diabetes Ferderation (IDF) has estimated that there will be almost 650 million adult diabetic patients worldwide at the end of the next 20 years (excluding patients over the age of 80). At this time, pancreas transplantation is the only available cure for selected patients, but it is offered only to a small percentage of them due to organ shortage and the risks linked to immunosuppressive regimes. Currently, exogenous insulin therapy is still considered to be the gold standard when managing diabetes, though stem cell biology is recognized as one of the most promising strategies for restoring endocrine pancreatic function. However, many issues remain to be solved, and there are currently no recognized treatments for diabetes based on stem cells. In addition to stem cell resesarch, several β-cell substitutive therapies have been explored in the recent era, including the use of acellular extracellular matrix scaffolding as a template for cellular seeding, thus providing an empty template to be repopulated with β-cells. Although this bioengineering approach still has to overcome important hurdles in regards to clinical application (including the origin of insulin producing cells as well as immune-related limitations), it could theoretically provide an inexhaustible source of bio-engineered pancreases

Postoperative pain management in non-traumatic emergency general surgery: WSES-GAIS-SIAARTI-AAST guidelines

Background Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. Material and methods An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. Conclusion Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies

Postoperative pain management in non-traumatic emergency general surgery : WSES-GAIS-SIAARTI-AAST guidelines

Background Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. Material and methods An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. Conclusion Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies.Peer reviewe

A Hepatic Scaffold from Decellularized Liver Tissue: Food for Thought

Allogeneic liver transplantation is still deemed the gold standard solution for end-stage organ failure; however, donor organ shortages have led to extended waiting lists for organ transplants. In order to overcome the lack of donors, the development of new therapeutic options is mandatory. In the last several years, organ bioengineering has been extensively explored to provide transplantable tissues or whole organs with the final goal of creating a three-dimensional growth microenvironment mimicking the native structure. It has been frequently reported that an extracellular matrix-based scaffold offers a structural support and important biological molecules that could help cellular proliferation during the recellularization process. The aim of the present review is to underline the recent developments in cell-on-scaffold technology for liver bioengineering, taking into account: (1) biological and synthetic scaffolds; (2) animal and human tissue decellularization; (3) scaffold recellularization; (4) 3D bioprinting; and (5) organoid technology. Future possible clinical applications in regenerative medicine for liver tissue engineering and for drug testing were underlined and dissected

Regenerative Medicine and Diabetes: Targeting the Extracellular Matrix Beyond the Stem Cell Approach and Encapsulation Technology

According to the Juvenile Diabetes Research Foundation (JDRF), almost 1. 25 million people in the United States (US) have type 1 diabetes, which makes them dependent on insulin injections. Nationwide, type 2 diabetes rates have nearly doubled in the past 20 years resulting in more than 29 million American adults with diabetes and another 86 million in a pre-diabetic state. The International Diabetes Ferderation (IDF) has estimated that there will be almost 650 million adult diabetic patients worldwide at the end of the next 20 years (excluding patients over the age of 80). At this time, pancreas transplantation is the only available cure for selected patients, but it is offered only to a small percentage of them due to organ shortage and the risks linked to immunosuppressive regimes. Currently, exogenous insulin therapy is still considered to be the gold standard when managing diabetes, though stem cell biology is recognized as one of the most promising strategies for restoring endocrine pancreatic function. However, many issues remain to be solved, and there are currently no recognized treatments for diabetes based on stem cells. In addition to stem cell resesarch, several β-cell substitutive therapies have been explored in the recent era, including the use of acellular extracellular matrix scaffolding as a template for cellular seeding, thus providing an empty template to be repopulated with β-cells. Although this bioengineering approach still has to overcome important hurdles in regards to clinical application (including the origin of insulin producing cells as well as immune-related limitations), it could theoretically provide an inexhaustible source of bio-engineered pancreases

Mesenchymal Stromal Cell on Liver Decellularised Extracellular Matrix for Tissue Engineering

Background: In end-stage chronic liver disease, transplantation represents the only curative option. However, the shortage of donors results in the death of many patients. To overcome this gap, it is mandatory to develop new therapeutic options. In the present study, we decellularised pig livers and reseeded them with allogeneic porcine mesenchymal stromal cells (pMSCs) to understand whether extracellular matrix (ECM) can influence and/or promote differentiation into hepatocyte-like cells (HLCs). Methods: After decellularisation with SDS, the integrity of ECM-scaffolds was examined by histological staining, immunofluorescence and scanning electron microscope. DNA quantification was used to assess decellularisation. pMSCs were plated on scaffolds by static seeding and maintained in in vitro culture for 21 days. At 3, 7, 14 and 21 days, seeded ECM scaffolds were evaluated for cellular adhesion and growth. Moreover, the expression of specific hepatic genes was performed by RT-PCR. Results: The applied decellularisation/recellularisation protocol was effective. The number of seeded pMSCs increased over the culture time points. Gene expression analysis of seeded pMSCs displayed a weak induction due to ECM towards HLCs. Conclusions: These results suggest that ECM may address pMSCs to differentiate in hepatocyte-like cells. However, only contact with liver-ECM is not enough to induce complete differentiation.</p

Postoperative pain management in non-traumatic emergency general surgery: WSES-GAIS-SIAARTI-AAST guidelines.

BACKGROUND: Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. MATERIAL AND METHODS: An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. CONCLUSION: Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies

Postoperative pain management in non-traumatic emergency general surgery: WSES-GAIS-SIAARTI-AAST guidelines

Background Non-traumatic emergency general surgery involves a heterogeneous population that may present with several underlying diseases. Timeous emergency surgical treatment should be supplemented with high-quality perioperative care, ideally performed by multidisciplinary teams trained to identify and handle complex postoperative courses. Uncontrolled or poorly controlled acute postoperative pain may result in significant complications. While pain management after elective surgery has been standardized in perioperative pathways, the traditional perioperative treatment of patients undergoing emergency surgery is often a haphazard practice. The present recommended pain management guidelines are for pain management after non-traumatic emergency surgical intervention. It is meant to provide clinicians a list of indications to prescribe the optimal analgesics even in the absence of a multidisciplinary pain team. Material and methods An international expert panel discussed the different issues in subsequent rounds. Four international recognized scientific societies: World Society of Emergency Surgery (WSES), Global Alliance for Infection in Surgery (GAIS), Italian Society of Anesthesia, Analgesia Intensive Care (SIAARTI), and American Association for the Surgery of Trauma (AAST), endorsed the project and approved the final manuscript. Conclusion Dealing with acute postoperative pain in the emergency abdominal surgery setting is complex, requires special attention, and should be multidisciplinary. Several tools are available, and their combination is mandatory whenever is possible. Analgesic approach to the various situations and conditions should be patient based and tailored according to procedure, pathology, age, response, and available expertise. A better understanding of the patho-mechanisms of postoperative pain for short- and long-term outcomes is necessary to improve prophylactic and treatment strategies