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Clinical Problem:
• Pelvic Organ Prolapse• Descent of bladder, uterus
or rectum below its normal anatomical level.
• Major Risk factors
Gravity
Gravidity
Obesity
Multiple pregnancies
Racial factors.
Epidemiology:
• Variable data – Loss of utero-vaginal support seen in 43-76%.• Women’s Health Initiative
– 41% of women over 50 show some amount of POP.– 34% had a cystocele, 19% rectocele and 14% uterine prolapse– Lifetime risk of undergoing surgery for SUI or POP is 11.1%– More than 300,000 procedures performed in the US annually for
POP.– About 13% of patients who undergo a surgery will require a repeat
procedure in 5 years.
• NCHS lists genital prolapse as one of the 3 most common causes for hysterectomy in women.
Clinical Problem:
• Urinary SymptomsIncontinence
Frequency
Urgency
• Vaginal SymptomsDyspareunia
Spotting
Discomfort
• Bowel SymptomsConstipation
Incontinence
Loss of Sensation
Current Solutions:
• Non SurgicalPelvic Floor Exercises
Vaginal Creams
Vaginal Pessaries
• Surgical Fascia tightening
Introducing Slings and Meshes
Hysterectomy Abdominal Vaginal
Current Solutions:
• Non SurgicalPelvic Floor Exercises
Vaginal Creams
Vaginal Pessaries
• Surgical Fascia tightening
Introducing Slings and Meshes
Hysterectomy Abdominal Vaginal
Standard of Care ( slings and meshes)
• Autografts• Allografts(cadaver)• Xenografts• Synthetic (non absorbable)
– Nanoporous (<1 micron)– Macroporous (<10 micron)– Macroporous (<10 micron)– Macroporous ( >75 micron)
• Materials– Polypropylene (LWPP v/s HWPP)– Polyester– PTFE– PLGA
Market:• Most major medical
device companies in this market.
• Mesh prices range from $250 - $1000.
• DRG Code reimbursement- $5800 to $17,280.
• Over 300,000 surgeries performed every year.
• Billion dollar market.• Higher Pricing –
possible.
Complications
• Biomechanical Reaction:Enzymatic degradation of the filaments leads to loss of mechanical strength.
Complications:
• Host responseInflammation, aggressive macrophage response, excessive fibrosis, contractures and scarring.
Complications:
• Host responseInflammation, aggressive macrophage response, excessive fibrosis, contractures and scarring.
Complications:
• Host responseInflammation, aggressive macrophage response, excessive fibrosis, contractures and scarring.
Side effects:
• Erosion and Extrusion through vaginal wall.
• Vaginal discharge and infections
• Perforation of pelvic organs
• Pelvic pain and dyspareunia
• Incontinence• Scarring• Recurrence of POP
Such a Mess:
• 2001 – FDA clears first surgical mesh for POP.• Late 2000s - 300,000 surgical repairs done every year.• High recurrence rate (6-29%)• Severe complications including erosions.• 2008- FDA issues a Public Health Notification cautioning
patients and physicians of S/E.• Over 100 synthetic meshes in the market.• 2011 – FDA receives over 4000 complaints(2005-10) of SAE.• Warning letter issued. Complications “not rare”.• 2012- First major recall by J&J.• 2015 – About 70,000 women have filed lawsuits.
Current Pelvic Mesh Solutions
Top Characteristics for pelvic mesh:
• Large pore size• Flexibility• High Tensile Strength• Toughness (absorbs energy)• Fibrous capsule formation
Pott et al. PLoS ONE 2012
Our Recommendation
• SF based start-up Spider Sense.
• Creates spider silk for medical applications.
• R&D for past 3 years.• Perfect biomaterial for slings
and meshes.• Future applications like
Ligament and skin scaffolds.• Spider silk already being
commercialized for clothing and other applications.
Other properties• Light weight (1.3 g/cm3)
• Sterilizable, can withstand approximately 250 [12,13].℃
• High supercontraction rate: absorption of water leads to tightening of thread to maintain rigidity.
• Silks have proven high antimicrobial properties, suggesting their use for medical application
• Spider fibers were well-tolerated up to 10 months in regeneration of sheep peripheral nerves in vivo
Subcutaneous Fibrotic Response: Vicryl vs. Trypsin-treated Spider Egg Sac Silk, 4 weeks
Vicryl Spider Silk
*=fibrotic response K Gellnyck et al. J mater Sci. 2008
Fibrotic Response: Silicone Implant vs. Spider protein-coated implant
PH Zeplin et al. Adv. Funct. Mater 2014
Biggest Challenge: Manufacturing and Scale-up
• Spiders are cannibals• Fibers from heterologous hosts require processing.• Failure to duplicate natural mechanical strength• Little known regarding the physiological properties of
spinning glands
Regulatory Pathway:
• Current Meshes are FDA approved.• Silk is FDA approved for many applications.• Seri-silk Scaffold by Serica approved in 2009.
Silk Proteins converted to multifilament fibers
Sericin extracted from fibers Purified fibers assembled into 3D
scaffolds.
Regulatory Pathway:
• Use Seri Scaffold as predicate device.
• Clinical Indication- P.O.P.• Apply for 510(k)
clearance.• Requirements:
• Bench top testing.• Biocompatibility
studies.• In vivo Rabbit studies.
• Estimated time: 12 -18 months.
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