Biopolymers in orthopedics

Polymers for use as biomaterials in orthopedics, in addition to the demand for biocompatibility and non-toxicity, must have appropriate degrees of thermoplasticity, strength, crystallinity, degradation characteristics and hydrophilicity . Following are the main polymers used as biomaterials in orthopaedic and other applcations.

Poly-L-Lactic Acid (PLLA).  Polymer-based absorbable implants were first used in the early 1960s when American Cyanamid developed Dexon, a polyglycol material that was used as a resorbable suturing material. It was commercialized by Davis and Geck in 1970. When blended with polylactic acid (PLA), polyglycol forms a copolymer structure that breaks down gradually in the presence of bodily fluids through hydrolysis. The main resorbable medical grade polymer in current use is Poly-L-Lactic Acid (PLLA). It is more hydrophobic than PLA or PGA and maintains its structure in the body for longer; it is used in the manufacture of interference screws, soft tissue anchors, urological stents, tacks and staples.

Polymethylmethacrylate (PMMA).  This is the most commonly used orthopedic cement, used primarily to anchor hip stems in hip arthroplasty operations. It is also commonly used in the treatment vertebral compression fractures.

Polytetrafluoroethylene (PTFE).  PTFE was discovered in 1938 by chemists at DuPont, but was not marketed until after World War II. It is a fluorinated carbon with a high molecular, partly crystalline structure, resistant to virtually all chemicals. It offers an extremely wide working temperature range, from -200 to +300 °C. Its surface is adhesion-resistant due to shielding of the carbon chain by fluorine atoms.

A major use of PTFE is to make the prosthesis for the Anterior Cruciate Ligament (ACL) repair procedure. The ACL has considerable strength and modulus due to an aligned type I collagen network that bears great loads while undergoing little deformation. However, while the ACL’s mechanical properties increase during development, they begin to deteriorate with age and may therefore need to be augmented by prosthesis.

PTFE is also used in graft augmentation devices to protect biological grafts. Its intended use is to be a temporary load-bearing device and it does not require long-term performance capability. Apart from its use in graft augmentation, PTFE is also used in microporous hydrophobic membranes (MHM) that are used in products such as vented blood warmers, in-line suction filters and vented suction containers.

Polyurethane The Polymer Technology Group produces polyurethane bionate, used in applications that have a potential mode of degradation such as pacemaker leads; also as base polymers for surface modification, known as surface modifying end groups (SMEs). SMEs can permanently modify surface properties, such as blood compatibility, abrasion resistance, coefficient of friction, and resistance to degradation in implants.

Polyvinyl chloride (PVC). Vinyl has proved to be one of the most successful modern synthetic materials; it is a polymer formed by chlorine (about 57 percent by weight), carbon and hydrogen. It is long-lasting and safe in production, use and disposal. Typical uses for vinyl in the healthcare field include blood and IV bags, dialysis tubing, catheters, labware, pressure monitoring tubing, breathing tubes and inhalation masks. Vinyl is durable, sterilizable, non-breakable and cost-effective.

Polydimethylsiloxane (PDMS or silicone).  Silicones are synthetic polymers with a linear repeating silicon-oxygen backbone. However, organic groups attached directly to the silicon atoms by carbon-silicon bonds prevent formation of the 3D network found in silica.. Silicone is used in a variety of fields such as medicines, food processing, and a wide range of medical devices as well as putty and sealants. Silicone oil is commonly used as a lubricant in syringes and blood giving sets. Silicones are used during surgery to repair retinal detachment. Silicones are also used for breast prosthesis and in topical applications.

Polyester.  Polyethylene terephthalate (PET)—linear and aromatic polyester—was first manufactured by DuPont in the late 1940s. It is still known by the original trade name of Dacron. Current medical applications of PET include implantable sutures, surgical mesh, vascular grafts, sewing cuffs for heart valves, and components for percutaneous access devices.

PET sutures have been used in the medical field for half a century and are especially valuable for critical procedures, where strength and stable performance over a long duration is necessary. Woven PET is used in surgical meshes for abdominal wall repair and in applications requiring surgical “patching.”

Synthetic vascular prostheses made of woven as well as knitted PET are used in the repair of the thoracic aorta, ruptured abdominal aortic aneurysms, and to replace iliac, femoral, and popliteal vessels. PET is also used as a sewing cuff around the circumference of the heart valves to promote tissue ingrowth and to provide a surface to suture the valve to the surrounding tissue. Percutaneous tunneled catheters also use PET cuff to stabilize catheter location and minimize bacterial migration through the skin.

Polymer Biomaterials Used in Orthopaedics

 

Polymer Type

Orthopaedic Application

PLLA, PGA, PLA

Soft Tissue Anchors, Screws, Staples

PMMA

Bone Cement

Polyurethane

Facial Prostheses

PDMS

Bones and Joints

Nylons

Joints

 

Source: MedMarket Diligence, LLC; Report #M625, "Emerging Trends, Technologies and Opportunities in the Markets for Orthopedic Biomaterials, Worldwide."

 

Bioresorbable Polymers

There is an increasing demand for biodegradable or bioresorbable fixation implants for use in procedures such as shoulder reconstruction, small joint fixation, meniscal repair and cruciate ligament fixation . The total number of such procedures in the USA is estimated to be more than 250,000 each year. The biodegradable polymers used to meet this demand include polyglycolide (PGA), polyglycolide-co-lactide, polylactic acid (PLA), and poly-L-lactic acid (PLLA).
 

Startup and early stage spine surgery companies

If there is a more robust area of medtech development — one with more success in creating clinical and market value while resisting pricing pressures — than spine surgery, I would be surprised.

The global spine market is large, active and growing rapidly in revenues. Several dynamic forces, in addition to the aging of the population, are expected to affect the market and treatments during the next several years. While spinal fusion will always have a place, its share of the treatment market is expected to decline. Newer treatments such as total disc replacement and nuclear arthroplasty will erode the spinal fusion market, as these and other treatments which preserve spinal motion gain favor over the invasive and traumatic fusion of two or more spine segments.

Early Stage / Startup Spine and Orthopedic Surgery Companies

 

Company

Year founded

Area of interest

3Cor Medical, Inc.

2002

Distraction screws for plating and interbody fusions.

Allez Spine LLC

2003

Pedicle screw systems and cervical plating systems for use in spine surgery.

AOI Medical, Inc.

2005

Develops innovative orthopedic medical devices for spine and trauma markets

Archus Orthopedics

2002

Total Facet Arthroplasty System® (TFAS®), an articulating joint prosthesis.

Baxano, Inc.

2005

Tools that restore spine function and preserve healthy tissue

Cartilix, Inc.

2004

Biomaterials for repair of tissues in articular joints.

CoreSpine Technology LLC

2005

Spinal arthroplasty

Creaspine

2005

Instrumentation and devices for use in spine surgery.

Custom Spine, Inc.

2003

To create the next generation of surgeon-friendly spinal implants.

Eden Spine, LLC

2006

Motion-preserving spine therapies.

Expandis Ltd.

2002

Minimally invasive orthopedic surgery instrumentation.

Facet Solutions, Inc.

2003

Facet arthroscopy

ForSight Labs, LLC

2005

Ophthalmic device company incubator

Globus Medical, Inc.

2003

To drive significant technological advancements across the complete suite of spinal products including Fusion, MIS, Motion Preservation and Biomaterials.

IB Medical LLC

2006

Static compress device technology in spine surgery.

Innovative Spinal Technologies, Inc.

2002

Spine surgery technologies.

InteliFUSE, Inc.

2005

Shape memory technology for bone fracture fixation/fusion and bone remodeling

MI4 Spine, LLC

2006

Minimally invasive spinal instrumentation.

NBI Development, Inc.

2007

Implantable spine neuromodulation devices.

OrthoMEMS, LLC

2005

Implant systems for spine and orthopedic applications using MEMS and wireless technology.

Ouroboros Inc.

2005

Medical devices for minimally invasive spinal fusion

Paradigm Spine, LLC

2005

Non-fusion interspinous spinal implant.

PNIR (Peripheral Nerve Injury Repair), LLC

2008

Implant technologies for peripheral nerve repair.

RE Spine, LLC

2007

Intervertebral disc and facet joint prosthesis in spine surgery.

Signus Medical LLC

2004

Pioneering the introduction of new biomaterials such as PEEK-Optima®, and research into the next generation of materials

Small Bone Innovations, LLC

2004

Orthopedic technology focus on small bones and joints (hand, wrist, elbow).

Spartek Medical, Inc.

2006

Motion preserving spine fusion implant, inserted minimally invasively, for treatment of degenerative disc disease.

Spinal Elements, Inc. (formerly Quantum Orthopedics, Inc.)

2003

Working with prominent surgeons to develop medical device technologies in the areas of spine arthroplasty (joint motion preservation) and spinal fusion.

Spine Form, LLC

2005

Medical device technology based on treatment of scoliosis.

SpineForm, LLC

2004

Spine staple

SpineFrontier, Inc.

2006

Spine implant technologies.

SpineMatrix, Inc.

2006

Spinal imaging to improve diagnosis of lower back pain.

SpineMedica Corp.

2005

Device technologies for spine and chronic back pain.

Spinus LLC

2005

Instruments for neurological, orthopedic and spine surgery.

Vertebral Technologies, Inc.

2005

Biocompatible polymers for joint restoration within the spine

Vertebron

2003

Developing several product for spinal fusion and fixation (arthrodesis), as well as new products and intellectual property (IP) that focus on motion preservation (arthroplasty) and dynamic stabilization.

Vertech, Inc.

2007

Device to ease the pain of compression fractures of the spine by separating spinal bones and injecting fast-hardening cement.

Vertiflex (fka DK Spine Technology, Inc.)

2004

Medical devices for spine surgery

Source:  MedMarket Diligence, Report #M510 (Worldwide Spine Surgery 2008-2017) and the Medtech Startups Database.

 

Criteria behind adoption of sealants, glues and other securement products, by specialty

The decision by physicians to make greater use of surgical sealants, glues, hemostats and anti-adhesion products ("securement products") for specific medical/surgical procedures is impacted by cost-effectiveness criteria as well as the substantial clinical benefit they offer. Below are described the four categories of surgical cases, distinguished through the level of clinical need and procedure enabling benefits, as well as the cost-effectiveness dynamics of the products. These categories are useful as predictors for uptake of existing approved adjunctive closure and securement products, as well as new products as they penetrate untapped markets in both the United States and the rest of the world.
 

Category I: Important and Enabling
Important to prevent excessive bleeding and transfusion, to ensure safe procedure, and to avoid mortality and to avoid complications associated with excessive bleeding and loss of blood.

Category II: Improved Clinical Outcome
Reduces morbidity due to improved procedure, reduced surgery time, and prevention of complications such as fibrosis, post-surgical adhesion formation, and infection (includes adjunct to minimally invasive surgery).

Category III: Cost-Effective and Time-Saving
Immediate reduction in surgical treatment time and follow-up treatments.

Category IV: Aesthetic and Perceived Benefits
Selection is driven by aesthetic and perceived benefits, resulting in one product being favored over a number of medically equivalent treatments.
 

Considering the categories above, we forecast relative procedure volume uptake by surgeons using securement products with varying rates driven by the benefits the products provide within different clinical specialties.

 

criteria-sealants 

Source: MedMarket Diligence’s Report #S175, "Worldwide Surgical Sealants, Glues, Wound Closure and Anti-Adhesion Markets, 2009-2013."

 

Applications of fibrin and other sealants

Fibrin and other sealant products have been approved and used outside the United States for many years and their use has created strong awareness of their surgical and economic benefits in Europe, Latin America and Asia. As a result, many such products have been marketed in these regions for up to 20 years and have been developed for a variety of surgical uses. While in the United States these products were approved initially as hemostatic adjuncts to suturing, they are increasingly being used for sealing of tissues, yet their use beyond hemostasis (i.e., as sealants and low-strength glues) lags that of markets outside the United States.

For the vast majority of surgical procedures, sutures and staples remain the most common methods of closure, but often they are sub-optimal. They do not have inherent sealing capabilities, and therefore cannot stop air and fluid leakage (for example in lung resection) and fluid leakage at the wound site. Furthermore, friable tissues such as the liver, brain or spleen, are fragile and often cannot support sutures or staples. Therefore, other means of wound closure are required for repair of these tissues.

However, the steady pace of FDA approvals and market introductions for products with sealing capabilities illustrates the success manufacturers have had in surmounting many of the technical hurdles to these products providing strong roles in tissue sealing. These include approvals by Baxter (Tisseel), Genzyme (FocalSeal), GluStitch (GluShield), Angiotech (CoSeal, Vitagel), CryoLife (BioGlue), and Syneture/Covidien (Indermil).
 

Applications of Fibrin Sealants and Other Surgical Sealants

  • Local hemostatic measures for both surgical and trauma cases
     
  • Surgery in patients with bleeding disorders (e.g., hemophilia, severe thrombocytopenia) and non-bleeding cases with suspected fluid oozing
     
  • Surgery in nonsuturable organs (e.g., brain, liver, lung, pancreas, thymus) or to repair unhealthy tissue (e.g., irradiated bowel or tissue of elderly patients)
     
  • Cardiovascular, microvascular surgery and vascular grafts (e.g., aneurysm repair, coronary bypass, etc.)
     
  • Nerve grafts
     
  • Skin grafts, particularly plastic surgery
     
  • Surgery of small or difficult to reach organs (e.g., tympanoplasty, ENT, eye)
     
  • Sealing of body cavities, fistulae, pneumothorax, cranium, etc.
     
  • Anastomosis of gastrointestinal, tract and other ductal organs

Source:  MedMarket Diligence, LLC; Report #S175

 

 

Drug-Eluting Balloon Catheters

[Through the course of researching and analyzing coronary artery disease treatments, technologies and markets for our May 2009 worldwide coronary stents market report, we have compiled data on the ancillary market of drug-eluting balloons, which we synopsize below.]

Drug-Eluting Balloons

A handful of companies are developing drug-coated balloon catheters as an alternative to balloon angioplasty and stenting and for those who would not benefit from PCI, such as those in whom antiplatelet therapy is neither recommended nor desired. 

The concept behind the technology is based on the assumption that delivering a rapid release of drugs into the arterial tissue is more effective than the gradual release of drugs, as seen with drug-eluting stents. Another side benefit of the technology would be significant cost-savings. Angioplasty balloons currently used typically cost roughly $400 each.

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Technologies/approaches being developed by specific companies include:

  • drug-coated angioplasty catheters for coronary and peripheral applications
  • development of paclitaxel-coated angioplasty catheter
  • coating standard angioplasty balloons with paclitaxel
  • bioabsorbable coating on balloon drug-eluting balloon catheter
  • mix of paclitaxel and hydrophilic spacer on balloon surface
  • paclitaxel-eluting balloon catheter for in-stent restenosis, bifurcated lesions, small diameter lesions, etc.
  • polymer-based drug delivery on balloon catheter
  • paclitaxel-eluting balloon catheter with controlled drug release for coronary and peripheral applications
  • drug-eluting balloon catheter with surface that penetrates, splits stenosis to facilitate drug delivery

 

 Developers of Paclitaxel-Eluting Balloon Catheters

See report #C245 for table of companies with products in development

Source:  MedMarket Diligence report #C245, "Worldwide Market for Drug-Eluting, Bare and Other Coronary Stents, 2008-2017." May 2009. 


Purchase for download:  Report #C245, "Worldwide Coronary Stents 2009, PDF" — $2,850.00
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Non-fusion spine surgery worldwide market growth

One of the most exciting areas in spinal surgery today is the non-fusion area. Surgeons and engineers are creating devices that can be implanted to treatment various spine conditions without fusion, thus allowing the patient to retain at least some movement and flexibility that would otherwise be lost by fusing vertebrae together. Although fusion is still the gold standard for, for example, treatment of DDD, more and more, non-fusion products, including dynamic stabilization devices (or motion preservation devices) and total disc replacement (TDR) are becoming the treatment of choice, especially for the younger, more active patient.

non-fusion-growth-rates 

Source: MedMarket Diligence, Report #M510, "Spine Surgery Worldwide, 2008-2017."

 

Non-fusion spine surgery technologies include disc arthroplasty (artificial spinal discs) and nuclear arthroplasty and nuclear disc prostheses (nucleus removal and annular repair devices).


See Report #M510, "Spine Surgery Worldwide."

Tissue closure and securement as benchmark for medical device usage

surgical-suturesThe market for surgical closure and securement (sealants, glues, sutures, staples, tapes, hemostasis, anti-adhesion) has entered a phase in which major driving forces are the introduction of new procedures and techniques by the surgical profession, the development by the medical device industry of new wound closure devices and biomaterials, and the growing willingness of surgical specialists to use these devices in appropriate circumstances. There is now a continuum between simple closure using sutures and the use of specially designed devices and delivery systems with new bioresorbable securement materials either as supplements to conventional closure methodology or as stand-alone replacements.

Worldwide expenditure on all medical devices is estimated to have surpassed $180 billion in 2007, and in the field of tissue repair and surgical securement, the total market reached $7.3 billion, underpinned by product advances reflecting our improved understanding of the underlying mechanisms of tissue repair, patient demographic pressures creating an increasing caseload of procedures, and a rapidly expanding number of new products available.

The tissue closure and securement market can be regarded as a benchmark indicator for overall expansion of medical device usage. This is because surgical closure and securement products are growing to be components of all surgical procedures. These products are used for rapid and efficient closure of surgical wounds, and internal securement of tissues to reduce pain and accelerate rehabilitation. Appropriate use of these products can reduce risk of infection, and can optimize the repair process to enhance the speed and strength of tissue repair, as well as reducing complications such as those resulting from post-surgical adhesions.

fibrin-sealantOverall industry spending in the health care system has a major impact on this segment. Consolidation in healthcare buying organizations (particularly in the United States) creates a pressure for cost-effectiveness arguments and supporting clinical efficacy data, and may also limit pricing potential, often when the overall cost in a category appears to be growing uncontrollably. The shift to outpatient and community-based treatment sites and practices affects the way that products are designed, marketed and distributed. In the securement segment, hospital administrators are involved in purchasing more routine and generic surgical securement and closure products, with surgeons selecting more advanced and new technologies. In addition, the case for cost-effectiveness involves professional preferences and adoption of new procedures, as well as the potential to reduce surgical theatre time and costs.

This field is expanding rapidly as new devices allow the surgeon to perform closure more quickly and with improved outcomes for patients. A significant premium is possible when new products and devices enable complex securement procedures to be performed under minimally invasive protocols with significant time-savings in the operating room. New technologies and new biomaterials allow improved tissue repair, and it is possible to revalue segments of this market based on significant improvements in clinical practice. We expect this market segment to triple in value over the next decade.

The total market potential by 2013, driven by procedure volumes, for hemostats, sealants, and glues, addressable by currently available products, nearly $4.5 billion for hemostats and sealants, and more than $1.3 billion for skin wound closure using high-strength glues. The introduction of a high-strength, elastic glue without toxicity concerns would revolutionize the market further and lead to even higher sales potential.

In the field of postoperative adhesion control, newly developed products improve on early prototypes and have substantial clinical efficacy data to allow for a significant premium cost. Over $700 million revenues were generated in 2007 in this market segment, and we expect that this market will grow to nearly $1.5 billion dollars in the next five years.


The above is excerpted from Report #S175.

 

 

Medtech market competitor consolidation on the rise

The healthcare industry faces a less daunting period of recession compared to many industries (we’ve covered it here and here), but still faces different and tough dynamics during this period.

Although demand for healthcare is more inelastic than other products and services, new business in healthcare (development and innovation) requires financing, a particularly  scarce commodity during the recession.  Well established companies with existing revenue streams are able to draw on those streams to fund new development.  However, early stage and startup companies demand financing from 3F ( "family, friends and fools"), since they do not yet have other revenue streams.  So, an obvious polarity is set up:  big companies with money seeking innovation versus small companies with innovation but little money.

Hence, the young startup has become a very real acquisition target by established companies.

If we look at one of our favorite markets, for surgical sealants, glues, hemostats, wound closure and anti-adhesion, here is a past list of acquisitions in this arena, a robust amount of activity before the financial meltdown took place: 

 

 

Company

Year Acquired

Omrix Biopharmaceuticals

2008

Altana Pharma

2007

American Medical Instruments

2006

Berlin Heart

2006

Biomet

2006

Confluent Surgical

2006

Quill Medical

2006

Surgical Specialties

2006

Closure Medical

2005

Aventis Behring

2004

Interpore Cross

2004

Onux Medical

2004

PPL Therapeutics

2004

Cohesion

2003

Gliatech

2003

Fusion Medical Technologies

2002

Medlogic Global

2002

Focal

2001

Source: MedMarket Diligence, LLC, Report #S175, "Worldwide Surgical Sealants, Glues and Wound Closure Market, 2009."

In early 2009, we have already seen some struggles among young companies in this sector, such as Haemacure, in financing their operations and continued development.  Given that there are so manny active companies in this area (our report #S175 profiles over 135 companies), we anticipate in 2009 a significant amount of interest and potentially acquisitions by the well established players.

See our report #S175 table of contents, including companies profiled, for potential acquisition targets.

 

Hemostasis in wound management

operating-room

Hemostatic agents have been used for over a hundred years to prevent bleeding in the surgical situation. Primarily these products were first introduced to prevent hematomas during surgery with the aim of preventing resultant infections. During the 1980s and 1990s, the popularity of hemostats increased rapidly as surgeons tried to avoid excessive use of blood transfusions for reasons of economy and the threat of disease transmission.  

Hemostat products can be classified in six subsegments depending on their active principle: thrombin, gelatin, collagen, fibrin, synthetic materials, and other miscellaneous products that exhibit additional attributes.

The barriers for entry to the hemostasis market are reducing as many companies develop formulations of collagen and gelatin formulations for world markets. Currently, over 50 companies worldwide have products on the market for hemostatic applications.  However, a number of proprietary products and formulations still face significant regulatory hurdles associated with their development and manufacture. Most of the companies currently offering hemostat products are also actively pursuing new technologies and regulatory submissions for new products. In addition, a number of new companies are progressing additional and new technologies to market.

Sales in topical absorbable hemostats are forecast to increase at a roughly 7.5% compound annual growth rate through 2013. This growth will be fuelled by increased incidence of surgery, greater adoption of these products within the European surgical environment, and the need for improved hemostasis products during minimally invasive surgical procedures.


Excerpted from Report #S175, "Worldwide Surgical Sealants, Glues and Wound Closure Market, 2009."

Wound closure, sealants, other securement sales in the Americas

Taken together, the Americas represent some 60% of the global market for surgical securement (sealants, glues, hemostasis, wound closure, anti-adhesion), led by the United States with more than 50%. The relative success of each product type varies between these markets, dominated by traditional sutures and staples, but with sealants rapidly penetrating and gaining share.

securement-americas

Source:  Report #S175, "Worldwide Surgical Sealants, Glues and Wound Closure Market, 2009-2013."