SBIR-STTR Award

Long term objectives: Laser Tissue Welding, Inc. focuses its research and product development in areas of innovative sutureless laser tissue welding using biodegradable and biocompatible biomaterials to join, repair and create hemostasis on surfaces of solid visceral organs such as the liver, spleen and kidney involved in trauma, cancer, and transplantation in the presence of dilutional coagulopathies or therapeutic anticoagulation. Specific Aims: Develop new manufacturing processes for 'Albumin-lndocyanine Solder' (AIS) and 'Denatured Albumin Scaffold' (DAS) two biomaterials required for laser tissue welding (LTW). This project will address the manufacturing process and its validation, design control, biocompatibility, gamma radiation sterilization validation, package strength and integrity, accelerated aging for regulatory purposes on a prototype basis. Research design and Methods: Develop and validate the manufacturing process for AIS and DAS biomaterials with processes that can be scaled up and automated. (Approximately 400 samples per product) Potential Technology innovation: The success factor for this technology is the development of a superior support structure made of biocompatible denatured human albumin that can be laser soldered. Anticipated outcomes: After successful prototype manufacturing and validation, we will scale up the manufacturing process to cGMP specifications and begin the regulatory approval process to begin human clinical trials.

Potential Commercial Applications:
These are trauma repair of the liver, spleen and kidney (200,000 case/year); liver tumors: primary hepatomas (22,000/yr), and rietastatic liver tumors (65,000/yr); split liver transplant (17,300 patients on the waiting list); partial nephrectomy for benign lesions (500/year); Urethral repair: for hypospadias, urethral stricture, urethral diverticulum, and urethral fistulae (600/yr) and skin approximation (all surgical procedures that currently use sutures) Relevance: 1) LTW will save lives due to its ability to quickly repair (minutes) and control hemorrhage from the surfaces of organs such as the spleen, liver, and kidney with minimal thermal injury. 2) Helps preserves and salvages organs such as liver, spleen, and kidney in trauma cases. 3) Blood conservation by reducing transfusion requirements. 4) Can be used laparoscopically for elective surgeries on liver and kidney

Long term objectives Laser Tissue Welding, Inc. (LTW) focuses its research and product development in areas of innovative sutureless laser tissue welding using biodegradable and biocompatible biomaterials to join, repair and seal tissues for controlling the leakage of a wide variety of fluids including blood, gastrointestinal fluids, urine, bile, lymph, and even cerebrospinal fluids. It is life saving when used on the surfaces of solid visceral organs, such as the liver spleen and kidney, involved in trauma, cancer and transplantation independent of coagulation factors and in presence of dilution coagulopathies or therapeutic anticoagulation. Proofs-of- concept in-vivo acute and chronic animal studies2, 23 and prototype biomaterial manufacture with validation of sterility, toxicity/biocompatibility and shelf-life have been completed under phase I SBIR. The next step is to conduct clinical safety and efficacy studies to support the FDA submission. Specific Aims I. Laser Tissue Welding compared to Radiofrequency ablation for surgical treatment of liver neoplasms A Clinical Safety and Efficacy Study Twenty patients will be treated with laser tissue welding and 20 randomized controls will be treated with open radiofrequency ablation (deep tissue coagulation) for treatment of primary and metastatic liver malignancies. The objective of this study will be to obtain a clinical safety and efficacy profile about laser tissue welding therapy in human subjects. I A. Safety will be assessed by tabulating the frequency of adverse events, such as postoperative morbidity due to secondary hemorrhage and hematoma; secondary infection and intra-abdominal abscess; prolonged biliary leak; compromised liver function, septicemia and mortality. I B. Efficacy will be determined by comparing treatment and controls with respect to the objective response rate based on the number of patients who achieve complete hemostasis, the time to hemostasis per cm2 area covered, intraoperative and postoperative blood loss (per day and number of days, blood product transfusion use (intraoperative and postoperative), postoperative bile leakage (per day and number of days); total operating room time, ICU stay, hospital stay and hospital costs. Time: 24 months Potential Technology innovation LTW has developed a combination of a process and two proprietary bioabsorbable human albumin products that are applied to seal tissues to stop fluid leaks (blood, bile and urine), during surgical repair of the liver and kidney.1, 2, 23 This combination device has laser precision with the versatility to seal tissues without thermal ablation of normal or abnormal tissues. Anticipated Outcomes After completion of FDA 510 (k) market approval with special controls (safety and efficacy clinical study) we will launch scaled-up manufacturing, undertake marketing and commercializing activities. Potential commercial applications LTW can be used to seal tissues for controlling the leakage of a wide variety of fluids including blood, gastrointestinal fluids, urine, bile, lymph, and even cerebrospinal fluids. Common groups include trauma repair and hemostasis of the liver (27,000 pts/yr); liver tumors: primary hepatomas (105,000/pts/yr), and metastatic liver tumors (595,000pts/yr); enable split liver transplants routinely or doubling donor organ pool (27,876pts/yr); partial nephrectomy for benign lesions (500/yr); urethral repair: for hypospadias, urethral stricture, urethral diverticulum, and urethral fistulae (600/yr) and skin/dermal approximation and all surgical procedures that currently use sutures.

Public Health Relevance:
Laser tissue welding (LTW) is an enhanced surgical capability that can seal low pressure fluid leaks instantly and accurately at will, including blood, gastrointestinal fluids, urine, bile, lymph, and cerebrospinal fluid. LTW is specifically useful when dealing with solid visceral organs with a soft friable parenchyma, such as the liver and kidney. It enables the surgeon to undertake resections in non-anatomical planes join and seal the parenchyma with minimal thermal damage. Relevance Laser Tissue Welding is an enhanced surgical capability, a new paradigm that can address important unmet medical needs. ' Saves lives: Quickly repairs and controls of hemorrhage in patients who cannot clot. ' Blood conservation: Reduced transfusion requirements. ' Salvages organs and tissues: Joins and seals without burning. ' Enabling curative surgical resection: Does not ablate tumors or normal parenchyma. Provides intraoperative tissue diagnosis of tumor free margins. ' Shorting operating time: Quick and accurate. ' Faster Healing and Shorter hospital stay: Due to decreased tissue trauma. ' Can be used in a contaminated environment29: Sterilizes contaminated wounds of drug-resistant super bugs like Methicillin-Resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes and Pseudomonas aeruginosa. ' Doubles the donor pool for liver transplantation: Simplifying split liver transplants. ' Fibro-optic capable: Minimally invasive laparoscopic & robotic applications.

Public Health Relevance Statement:


Project narrative:
Laser tissue welding (LTW) is an enhanced surgical capability that can seal low pressure fluid leaks instantly and accurately at will, including blood, gastrointestinal fluids, urine, bile, lymph, and cerebrospinal fluid. LTW is specifically useful when dealing with solid visceral organs with a soft friable parenchyma, such as the liver and kidney. It enables the surgeon to undertake resections in non-anatomical planes join and seal the parenchyma with minimal thermal damage. Relevance Laser Tissue Welding is an enhanced surgical capability, a new paradigm that can address important unmet medical needs. ¿ Saves lives: Quickly repairs and controls of hemorrhage in patients who cannot clot. ¿ Blood conservation: Reduced transfusion requirements. ¿ Salvages organs and tissues: Joins and seals without burning. ¿ Enabling curative surgical resection: Does not ablate tumors or normal parenchyma. Provides intraoperative tissue diagnosis of tumor free margins. ¿ Shorting operating time: Quick and accurate. ¿ Faster Healing and Shorter hospital stay: Due to decreased tissue trauma. ¿ Can be used in a contaminated environment29: Sterilizes contaminated wounds of drug-resistant super bugs like Methicillin-Resistant Staphylococcus aureus (MRSA), Streptococcus pyogenes and Pseudomonas aeruginosa. ¿ Doubles the donor pool for liver transplantation: Simplifying split liver transplants. ¿ Fibro-optic capable: Minimally invasive laparoscopic & robotic applications.

Project Terms:
Abdominal Abscess; Abscess, Intra-Abdominal; Abscission; Active Follow-up; Acute; Address; Adverse Experience; Adverse event; Albumins; Animals; Anticoagulation; Ar element; Area; Argon; Benign; Bile; Bile Juice; Bile fluid; Biliary; Biocompatible; Biocompatible Materials; Biomaterials; Bleeding; Blood; Blood Clot; Blood Clotting; Blood Coagulation Disorders; Blood Coagulation Factor; Blood Loss, Postoperative; Blood Poisoning; Blood coagulation; Body Tissues; Burn injury; Burns; Cancers; Carcinoma of the Liver Cells; Cerebrospinal Fluid; Chronic; Clinical; Clinical Research; Clinical Study; Clinical Trials; Clinical Trials, Unspecified; Clotting; Coagulation; Coagulation Disorder; Coagulation Factors; Coagulation Process; Coagulopathy; Data; Dermal; Devices; Diagnosis; Diathermy; Drug resistance; Electromagnetic, Laser; Evaluation; Excision; Extirpation; Extravasation; FLR; Failure (biologic function); Fistula; Frequencies (time pattern); Frequency; Goals; Government; Grafting, Liver; Grant; HCC; Head; Healed; Hematoma; Hemorrhage; Hemostasis; Hemostatic function; Hepatocellular Carcinoma; Hepatocellular cancer; Hepatoma; Hospital Costs; Human; Human, General; Hypospadia; Hypospadias; In Vitro; Kidney; Lasers; Leakage; Length of Stay; Lesion; Life; Liquid substance; Liver; Liver Transplant; Liver neoplasms; Lymph; MRSA; Malignant Neoplasms; Malignant Tumor; Man (Taxonomy); Man, Modern; Marketing; Mediating; Medical; Methicillin Resistant S. Aureus; Methicillin Resistant Staphylococcus Aureus; Methods; Morbidity; Morbidity - disease rate; Mortality; Mortality Vital Statistics; Necrosis; Necrotic; Neoplasms, Hepatic; Nephrectomy; Normal Tissue; Normal tissue morphology; Number of Days in Hospital; Operating Rooms; Operation; Operative Procedures; Operative Surgical Procedures; Optics; Organ; Organ Donor; Outcome; P. aeruginosa; P.aeruginosa; Patients; Persons; Phase; Post-Operative; Post-Operative Hemorrhage; Postoperative; Postoperative Bleeding; Postoperative Hemorrhage; Postoperative Period; Pressure; Pressure- physical agent; Primary carcinoma of the liver cells; Process; Pseudomonas aeruginosa; Pseudomonas pyocyanea; RF ablation; Radiation, Laser; Radio Frequency Ablation; Radiofrequency Ablation; Radiofrequency Interstitial Ablation; Randomized; Removal; Research; Reticuloendothelial System, Blood; Reticuloendothelial System, Lymph; Reticuloendothelial System, Spleen; Robotics; S. pyogenes; S.pyogenes; SBIR; SBIRS (R43/44); Safety; Secondary to; Septicemia; Skin; Small Business Innovation Research; Small Business Innovation Research Grant; Solid; Spillage; Spleen; Sterility; Streptococcus Group A; Streptococcus pyogenes; Surface; Surgeon; Surgical; Surgical Interventions; Surgical Procedure; Surgical Removal; Surgical sutures; Sutures; TRNSF; Technology; Therapeutic; Therapeutic Effect; Thermal Ablation Therapy; Time; Time Study; Tissues; Toxic effect; Toxicities; Transfusion; Transplantation of liver; Transplantation, Hepatic; Trauma; Urethra; Urethral Diverticulum; Urethral Stenosis; Urethral Stricture; Urinary System, Kidney; Urinary System, Urine; Urine; Validation; Vascular blood supply; Visceral; Welding; Weldings; Wound Healing; Wound Repair; base; biocompatibility; biomaterial compatibility; blood loss; blood product; blood supply; body system, hepatic; cancer transplantation; clinical investigation; clotting disorder; clotting factor; commercial application; drug resistant; failure; fluid; follow-up; gastrointestinal; healing; hepatic neoplasia; hepatic neoplasm; hospital days; hospital length of stay; hospital stay; human subject; in vivo; innovate; innovation; innovative; liquid; liver function; liver transplantation; liver tumor; lymphatic fluid; malignancy; manufacturing scale-up; methicillin resistant Staphylococcus aureus (organism); minimally invasive; neoplasm/cancer; organ system, hepatic; pressure; prevent; preventing; product development; prototype; public health relevance; randomisation; randomization; randomly assigned; renal; repair; repaired; resection; resistance to Drug; resistant to Drug; response; restoration; scaffold; scaffolding; seal; secondary infection; septicaemia; spinal fluid; sterile; success; surgery; thermal ablation; tissue repair; tissue trauma; tissue welding; trial comparing; tumor; urethra stricture; urethral; vascular supply