SBIR-STTR Award

Annually, over 1.2 million CT-guided lung biopsies are performed worldwide for lung cancer diagnosis (~400,000 in the US). Pneumothorax (PTX) - a collapsed lung, is the most common complication of this procedure, occurring in 20-40% of all CT-guided lung biopsies. In 10-15% of lung biopsies, the patient becomes symptomatic due to PTX and requires an invasive chest tube insertion, the definitive treatment for PTX. This complication costs, on an average, $15k per chest tube insertion and $1.3 billion worldwide to treat. This turns a same-day diagnostic procedure into a multi-day hospitalization. In addition to extreme respiratory distress to patients, it is inconvenient for radiologists to manage. PTX arises when air from the lungs or external environment enters the area between the chest wall and lungs during or after needle insertion due to a pressure difference. A recent time dependent analysis of 3,251 patients undergoing CT-guided lung biopsy demonstrated that ~75% of PTX occur while the needle is inserted (meaning air is actively leaking during the procedure). Several methods are used for preventing PTX due to biopsy, including only FDA approved device, blood/saline patch and air aspiration. All of these methods, however, are for application to the puncture site once the biopsy is complete and therefore relatively ineffective (<50%). Additionally, they add time (>10mins) and steps (>5) to the procedure. The development of a novel biopsy needle tract biosealant that will reduce or eliminate pneumothorax would be most valuable. The focus of the current investigation is to evaluate and demonstrate the possibility of using a biosealant and delivery device to seal needle tracts to prevent PTX during transthoracic lung biopsy. Further, win-vitro and in-vivo preliminary biocompatibility of the material as well as efficacy of the delivery device as compared to the current standard of care.

Public Health Relevance Statement:
Project Narrative This research will support the development of a medical device that will help clinicians reduce lung collapse rates during transthoracic lung biopsy, which will improve patient outcomes and satisfaction while reducing medical costs.

Project Terms:
Adhesions; Aging; Air; Biocompatible Materials; biological material; Biomaterials; Biological Assay; Biologic Assays; Bioassay; Assay; Biomechanics; biomechanical; Biopsy; Needle biopsy procedure; needle biopsy; Blood; Blood Reticuloendothelial System; Cell Body; Cells; chemical synthesis; Chest Tubes; Complication; Cytostatic Drugs; Cytostatic Agents; Cytostatics; Environment; Fibroblasts; Gel; Goals; Hospital Admission; Hospitalization; In Vitro; pulmonary; Lung Respiratory System; Lung; Medical Device; Methods; Murine; Mice Mammals; Mice; Mus; Needles; Patient Satisfaction; Client satisfaction; Patients; pneumothorax disorder; Pneumothorax; Polymers; pressure; Punctures; Puncture procedure; Research; Safety; Saline Solution; Saline; seal; suid; porcine; Swine; Suidae; Pigs; Family suidae; Testing; Time; Body Tissues; Tissues; Toxicology; Trocars; X-Ray Medical Imaging; X-Ray Imaging; Roentgenography; Radiography; Diagnostic X-Ray Radiology; Diagnostic X-Ray; Diagnostic Radiology; Conventional X-Ray; Diagnostic radiologic examination; genipin; Injectable; medical costs; Medical Care Costs; Risk Assessment; Custom; Chitosan; Poliglusam; base; improved; Procedures; Chest wall structure; Thoracic Wall; Chest Wall; Site; Area; Phase; Variant; Variation; Medical; Ensure; Chemicals; Malignant neoplasm of lung; lung cancer; Pulmonary malignant Neoplasm; Pulmonary Cancer; Malignant Tumor of the Lung; radiologist; Investigation; Diagnostic Procedure; Diagnostic Technique; Diagnostic Method; Hour; System; Respiratory distress; Operative Surgical Procedures; surgery; Surgical Procedure; Surgical Interventions; Surgical; Operative Procedures; biomaterial compatibility; biocompatibility; cytotoxicity; Lytotoxicity; success; Toxic effect; Toxicities; novel; Devices; Modeling; Property; cancer diagnosis; preventing; prevent; in vivo; Patient-Focused Outcomes; Patient-Centered Outcomes; Patient outcome; Small Business Innovation Research Grant; Small Business Innovation Research; SBIR; Validation; Monitor; Preparation; Development; developmental; safety study; Pathway interactions; pathway; cost; Outcome; Resistance; resistant; comparative; FDA approved; standard of care; Sterilization; Formulation; Injections; animal safety

Annually, over 1.2 million CT-guided lung biopsies are performed worldwide for lung cancer diagnosis (~400,000 in the US). Pneumothorax (PTX), a collapsed lung, is the most common complication of this procedure, occurring in 20-40% of all CT-guided lung biopsies. In 10-15% of lung biopsies, the patient becomes symptomatic due to PTX and requires an invasive chest tube insertion, the definitive treatment for PTX. This complication costs, on an average, $15k per chest tube insertion and $1.3 billion worldwide to treat. This turns a same-day diagnostic procedure into a multi-day hospitalization. In addition to extreme respiratory distress to patients, it is inconvenient for radiologists to manage. PTX arises when air from the lungs or external environment enters the area between the chest wall and lungs during or after needle insertion due to a pressure difference. A recent time dependent analysis of 3,251 patients undergoing CT-guided lung biopsy demonstrated that ~75% of PTX occur while the needle is inserted (meaning air is actively leaking during the procedure). Several methods are used for preventing PTX due to biopsy, including the only FDA approved device, blood/saline patch and air aspiration. All of these methods, however, are for application to the puncture site once the biopsy is complete and are therefore relatively ineffective (<50%). Additionally, they add time (>10mins) and steps (>5) to the procedure. The development of a novel biopsy needle track biosealant that will reduce or eliminate PTX would be most valuable. The focus of the current investigation is to evaluate and demonstrate the possibility of using a biosealant and delivery device to seal needle tracks and prevent PTX during transthoracic lung biopsy. Further, in-vitro and in-vivo biocompatibility of the material as well as efficacy of the delivery device as compared to the current standard of care will be assessed. Data from the Phase 1 program supports that an injectable hydrogel formulation can successfully prevent PTX in animal studies, and that candidate formulations show no adverse biological activity. In this Phase 2 proposal, we intend to refine the formulation for improved surgical performance and validate it with an animal model to demonstrate both efficacy and safety.

Public Health Relevance Statement:
Project Narrative This research will support the development of a medical device based on an injectable lung sealant that will help clinicians reduce lung collapse rates during transthoracic lung biopsy, which will improve patient outcomes and satisfaction while reducing medical costs.

Project Terms:
Air; Animals; Behavior; Biocompatible Materials; Biomaterials; biological material; Biopsy; Needle biopsy procedure; needle biopsy; Blood; Blood Reticuloendothelial System; Chest Tubes; Complication; Environment; Gel; Grant; Hospitalization; Hospital Admission; In Vitro; Lead; Pb element; heavy metal Pb; heavy metal lead; Lung; Lung Respiratory System; pulmonary; Medical Device; Methods; Needles; Patient Satisfaction; Client satisfaction; Patients; pneumothorax disorder; Pneumothorax; pressure; Punctures; Puncture procedure; Research; Safety; Saline Solution; Saline; seal; Testing; Time; Viscosity; Work; Injectable; Medical Care Costs; medical costs; base; improved; Procedures; Chest wall structure; Chest Wall; Thoracic Wall; Site; Area; Phase; Biological; biologic; Chemicals; Malignant Tumor of the Lung; Pulmonary Cancer; Pulmonary malignant Neoplasm; lung cancer; Malignant neoplasm of lung; radiologist; Life; programs; Investigation; Diagnostic Method; Diagnostic Technique; Diagnostic Procedure; System; Respiratory distress; Operative Procedures; Surgical; Surgical Interventions; Surgical Procedure; surgery; Operative Surgical Procedures; biocompatibility; biomaterial compatibility; Performance; success; Animal Models and Related Studies; model of animal; model organism; Animal Model; Hydrogels; novel; Modality; Devices; Reporting; Radiation; Modeling; Property; cancer diagnosis; preventing; prevent; Data; in vivo; Patient-Focused Outcomes; Patient outcome; Patient-Centered Outcomes; Validation; Development; developmental; preclinical study; pre-clinical study; cost; healing; design; designing; Outcome; usability; FDA approved; standard of care; efficacy testing; phase 1 study; Phase I Study; screening; Formulation; experimental study; experiment; experimental research; efficacy study; Injections; porcine model; pig model; piglet model; swine model; sealant