Vascular System Injuries

Researchers say they created a method to bond layers made of the same or different types of hydrogels and other polymeric materials. A team at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) conducted this research. They created a simple, versatile method to instantly and effectively bond those layers using a thin film of chitosan. Chitosan, a fibrous, sugar-based material comes from the processed outer skeletons of shellfish. The team successfully applied their new approach to a number of unsolved medical problems. They used it to protectively cool tissues, seal vascular injuries and prevent unwanted “surgical adhesions” of internal body surfaces that should not stick to each other. The team published their results in the Proceedings of the National Academy of Science (PNAS). “Chitosan films with their abilities to effectively assemble, fine-tune, and protect hydrogels in the body and beyond, open numerous new opportunities to create devices for regenerative medicine and surgical care,” says senior author and founding Wyss Institute core faculty member David Mooney, “The speed, ease, and effectiveness with which they can be applied makes them highly versatile tools and components for in vivo assembly processes in often short time-windows during surgeries, and the simple fabrication of complex biomaterial structures in manufacturing facilities.” Co-first author and former Wyss Research Associate Benjamin Freedman spearheaded “Tough Adhesives” development with Mooney. They aimed to develop a collection of regenerative medicine approaches using stretchable hydrogels. The team wanted to facilitate wound healing and tissue regeneration. Freedman said they wanted to combine two or more hydrogels in complex assemblies in a fast, safe and simple process. Through a biomaterial screening approach, they came upon chitosan. They found that the films achieved rapid and strong bonding of hydrogels through chemical and physical interactions that are different from those involved in traditional hydrogel bonding methods. Rather than create new chemical bonds, chitosan’s sugar strands rapidly absorb water between hydrogel layers. They entangle themselves with the polymer stands of hydrogels, forming multiple bonds. That creates adhesive forces between hydrogels that exceed those made by traditional approaches. The researchers set out to test their method on different medical applications. They showed that the adhesives could be wrapped around cylindrical shapes like an injured finger as self-adhering bandages for improved wound care. This application also allowed the local cooling of the underlying human skin. Wyss says this could lead to alternative burn treatments. Additionally, the team wrapped hydrogels whose surfaces were modified with thin chitosan films seamlessly around bowel, tendon and peripheral nerve tissue without bonding to the tissues themselves. “This approach offers the possibility to effectively insulate tissues from each other during surgeries, which otherwise can form ‘fibrotic adhesions’ with sometimes devastating consequences. Their prevention is an unmet clinical need that commercial technologies cannot adequately address yet,” said Freedman.

Hydrogels are already used in clinical practice for the delivery of drugs, and as lenses, bone cement, wound dressings, 3D scaffolds in tissue engineering and other applications. However, bonding different hydrogel polymers to one another has remained a challenge; yet it could enable numerous new applications. Now, researchers have pioneered a new method that uses a thin film of chitosan, a fibrous sugar-based material derived from the processed outer skeletons of shellfish, to make different hydrogels instantaneously and strongly stick to each other. They used their approach to locally protect and cool tissues, seal vascular injuries, and prevent unwanted 'surgical adhesions' of internal body surfaces. Hydrogels are versatile biomaterials conquering an increasing number of biomedical areas. Consisting of water-swollen molecular networks that can be tailored to mimic the mechanical and chemical features of various organs and tissues, they can interface within the body and on its outer surfaces without causing any damage to even the most delicate parts of the human anatomy. Hydrogels are already used in clinical practice for the therapeutic delivery of drugs to fight pathogens; as intraocular and contact lenses, and corneal prostheses in ophthalmology; bone cement, wound dressings, blood-coagulating bandages, and 3D scaffolds in tissue engineering and regeneration. However, attaching hydrogel polymers quickly and strongly to one another has remained an unresolved unmet need as traditional methods often result in weaker adhesion after longer-than-desired adhesion times, and rely on complex procedures. Achieving rapid adhesion of polymers could enable numerous new applications, including, for example, hydrogels whose stiffness could be finely tuned to better conform to specific tissues, on-demand encapsulation of flexible electronics for medical diagnostics, or the creation of self-adhesive tissue wraps for hard-to-bandage parts of the body. Now, scientists at the Wyss Institute for Biologically Inspired Engineering at Harvard University and Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have created a simple and versatile method to instantly and effectively bond layers made of the same or different types of hydrogels and other polymeric materials, using a thin film of chitosan: a fibrous, sugar-based material derived from the processed outer skeletons of shellfish. They successfully applied their new approach to several unsolved medical problems, including the local protective cooling of tissues, sealing of vascular injuries, and prevention of unwanted "surgical adhesions" of internal body surfaces that should not stick to each other. The findings are published in the Proceedings of the National Academy of Science (PNAS[BB1] ). "Chitosan films with their abilities to effectively assemble, fine-tune, and protect hydrogels in the body and beyond, open numerous new opportunities to create devices for regenerative medicine and surgical care," said senior author and Founding Wyss Institute Core Faculty member David Mooney, Ph.D. "The speed, ease, and effectiveness with which they can be applied makes them highly versatile tools and components for in vivoassembly processes in often short time-windows during surgeries, and the simple fabrication of complex biomaterial structures in manufacturing facilities." Mooney also is the Robert P. Pinkas Family Professor of Bioengineering at SEAS. Engineering a new bond Over the past years, Mooney's team at the Wyss Institute and SEAS has developed "Tough Adhesives," a collection of regenerative medicine approaches that use stretchable hydrogels to facilitate wound healing and tissue regeneration by strongly sticking to wet tissue surfaces and conforming to tissues' mechanical properties. "Precisely formulated Tough Adhesives and non-adhesive hydrogels give us and other researchers new opportunities to improve patient care. But to take their functionalities one or even multiple steps further, we wanted to be able to combine two or more hydrogels in more complex assemblies, and to do this fast, safely, and in a simple process," said co-first author and former Wyss Research Associate Benjamin Freedman, Ph.D., who spearheaded several Tough Adhesive developments with Mooney. "Existing methods to instantly bond hydrogels or elastomers had striking disadvantages because they relied on toxic glues, the chemical functionalization of their surfaces, or other complex procedures." Through a biomaterial screening approach, the team identified bridging films completely made of chitosan. Chitosan is a sugary polymer that can be easily made from the chitin shells of shellfish and has already found its way into wide-ranging commercial applications. For example, it is currently used to treat seeds and as a biopesticide in agriculture, to prevent spoilage in winemaking, in self-healing paint coatings, and in medical wound management. The team found that chitosan films achieved rapid and strong bonding of hydrogels through chemical and physical interactions that are different from those involved in traditional hydrogel bonding methods. Instead of creating new chemical bonds based on the sharing of electrons between individual atoms (covalent bonds), induced by a tiny shift in pH, chitosan's sugar strands rapidly absorb water residing between hydrogel layers and entangle themselves with the polymer stands of hydrogels, forming multiple bonds via electrostatic interactions and hydrogen bonding (non-covalent bonds). This results in adhesive forces between hydrogels that significantly exceed those created through traditional hydrogel bonding approaches. First applications To demonstrate the breadth of potential of their new method, the researchers focused on very different medical challenges. They showed that Tough Adhesives modified with chitosan films could now be easily wrapped around cylindrical shapes like an injured finger as self-adhering bandages to provide improved wound care. Due to the high water content of chitosan-bonded hydrogels, their application also allowed the local cooling of underlying human skin, which in the future could lead to alternative burn treatments. The researchers also wrapped hydrogels (tough gels) whose surfaces were modified with thin chitosan films seamlessly around bowel, tendon, and peripheral nerve tissue without bonding to the tissues themselves. "This approach offers the possibility to effectively insulate tissues from each other during surgeries, which otherwise can form 'fibrotic adhesions' with sometimes devastating consequences. Their prevention is an unmet clinical need that commercial technologies cannot adequately address yet," explained Freedman. In another application, they layed down a thin chitosan film on a tough gel that was already placed on an injured pig aorta ex vivo as a wound sealant to increase the overall strength of the bandage, which was exposed to the cyclical mechanical forces of blood pulsing through the vessel. "The numerous possibilities emerging from this study by Dave Mooney's group add a new dimension to the engineering of biomedical hydrogel devices, which could lead to elegant solutions for urgent unmet problems in regenerative and surgical medicine that many patients could benefit from," said Wyss Founding Director Donald Ingber, M.D., Ph.D., who is also the Judah Folkman Professor of Vascular Biology at Harvard Medical School and Boston Children's Hospital, and the Hansjörg Wyss Professor of Bioinspired Engineering at SEAS. Additional authors on the study are co-first author Juan Cintron Cruz, Mathew Lee, and James Weaver at the Wyss Institute and SEAS; Phoebe Kwon, Haley Jeffers, and Daniel Kent at SEAS; and Kyle Wu at Beth Israel Deaconess Medical Center in Boston. The study was supported by the Wyss Institute at Harvard University, the National Institutes of Health's National Institute on Aging (under award# K99/R00AG065495), and the Harvard GSAS Research Scholar initiative.

– BLA submission supported by results from Phase 2/3 clinical trial and outcomes of real-world use of the HAV under a Humanitarian Aid Program to treat wartime trauma injuries in Ukraine – – The HAV had higher rates of patency, and lower rates of amputation and infection, compared to historic synthetic graft benchmarks – – PDUFA date set for August 10, 2024 – Feb. 09, 2024 -- Humacyte, Inc. (Nasdaq: HUMA), a clinical-stage biotechnology platform company developing universally implantable, bioengineered human tissue at commercial scale, today announced that the U.S. Food and Drug Administration (FDA) has accepted and granted Priority Review to Humacyte’s Biologics License Application (BLA) seeking approval of the Human Acellular Vessel (HAV) in urgent arterial repair following extremity vascular trauma when synthetic graft is not indicated, and when autologous vein use is not feasible. The Prescription Drug User Fee Act (PDUFA) date, the FDA action date for their regulatory decision regarding the BLA, is August 10, 2024. This targeted PDUFA date is based on the Priority Review grant, which is a mechanism reserved by FDA for products that, if approved, would significantly improve the treatment, diagnosis, or prevention of serious conditions. Priority Review applications have a six-month review time instead of ten months for a standard review. The Priority Review aligns with the Regenerative Medicine Advanced Therapy (RMAT) designation granted by the FDA in May 2023 for urgent arterial repair following extremity vascular trauma. The Priority Review is also consistent with the priority designation given by the Secretary of Defense under Public Law 115-92, which was enacted to expedite the FDA’s review of products that are intended to diagnose, treat or prevent serious or life-threatening conditions facing American military personnel. “We are very pleased that the FDA has accepted our BLA and has recognized the potential importance of the HAV technology by granting us Priority Review,” said Laura Niklason, MD, PhD, Chief Executive Officer of Humacyte. “The BLA acceptance brings us a major step closer to our goal of providing an innovative regenerative medicine product for patients suffering traumatic vascular injury. Many patients with severe injuries are underserved by the current standard of care, and we are proud of the results that have been seen in our clinical trials and real-world humanitarian efforts.” The BLA submission is supported by positive results from the V005 Phase 2/3 clinical trial, as well as real-world evidence from the treatment of wartime injuries in Ukraine under a Humanitarian Aid Program supported by the FDA. The HAV was observed to have higher rates of patency (blood flow), and lower rates of amputation and infection, as compared to historic synthetic graft benchmarks. The HAV, a bioengineered tissue, is under investigation as a universally implantable vascular replacement that does not require immune suppression and that resists infection after implantation. Designed to be ready off-the-shelf, the HAV has the potential to save valuable time for surgeons who treat injured patients, and to improve outcomes and reduce complications. The HAV can be produced at commercial scale in Humacyte’s existing manufacturing facilities, which are expected to have the capacity to provide thousands of vessels for treating patients in need. The HAV has accumulated more than 1,200 patient-years of experience worldwide in a series of clinical trials in multiple indications, including vascular trauma repair, arteriovenous access for hemodialysis, and peripheral artery disease. The HAV is an investigational product and has not been approved for sale by the FDA or any other regulatory agency. Humacyte, Inc. (Nasdaq: HUMA) is developing a disruptive biotechnology platform to deliver universally implantable bioengineered human tissues, advanced tissue constructs, and organ systems designed to improve the lives of patients and transform the practice of medicine. The Company develops and manufactures acellular tissues to treat a wide range of diseases, injuries, and chronic conditions. Humacyte’s initial product candidates, a portfolio of HAVs, are currently in late-stage clinical trials targeting multiple vascular applications, including vascular trauma repair, arteriovenous (AV) access for hemodialysis, and peripheral artery disease. Preclinical development is also underway in coronary artery bypass grafts, pediatric heart surgery, treatment of type 1 diabetes, and multiple novel cell and tissue applications. Humacyte’s 6mm HAV for AV access in hemodialysis was the first product candidate to receive the FDA’s RMAT designation and has also received FDA Fast Track designation. Humacyte’s 6mm HAV for urgent arterial repair following extremity vascular trauma also has received an RMAT designation. The HAV received priority designation for the treatment of vascular trauma by the U.S. Secretary of Defense. For more information, visit www.Humacyte.com. The content above comes from the network. if any infringement, please contact us to modify.