About our project

Broken Bones? Let’s Start at the Top.

The Problem We Solve

Scientists and physicians at Bonenta have developed what could be the first synthetic bone graft implant for the skull that converts into your own bone over time. Your own bone! This is a really big deal to the millions of injured civilians and soldiers with head trauma who, currently, have to make the problematic choice between leaving a hole in the skull bone or getting a titanium (metal) plate, a plastic plug, cement, or several extra surgeries to move another bone to the head, all of which involve limitations and potential life-long complications.

The Pitch

We all know somebody who has had to get a bone graft, Bone and bone grafts are the second most implanted materials in the body (after blood transfusions). Unfortunately for trauma or accident victims and soldiers with open skull damage, there is not a good synthetic bone graft product to repair the damaged skull; if there were, it would be the treatment of choice. Bonenta, Inc. has developed and tested a powerful synthetic bone graft implant for the skull. Importantly, Bonenta’s new cranial bone graft implant brings sophisticated bone-growing activity that neurosurgeons find very agreeable to size, shape, place, and stabilize. Just as importantly, the bone-growing activity remains at the site of the implanted bone graft and does not diffuse away in dangerously high concentrations as can occur with the first-generation synthetic biological bone graft product (InFuse from Medtronic). For this and other reasons Bonenta’s bone graft was 5 times more effective in head-to-head preliminary testing with InFuse. Because of Bonenta’s patented technology, the active components that make our new cranial bone graft so exceptional allow the use of lower (safer) doses than in the first-generation product and they naturally signal the appropriate end of bone growth stimulation. Finally, our product was developed to be freeze-dried, meaning it can be cost-effectively distributed and stored for extended periods making it more appealable world-wide. US and pending international patents should allow Bonenta’s new cranial bone graft implant to penetrate a significant portion of the big synthetic bone graft market once approved. We could, potentially, help a lot of people. The first step in that approval process is the completion of a pilot human clinical trial to demonstrate both safety and effectiveness and we seek the funds to reach that goal.

How Bonenta’s Cranial Bone Graft Implant Works

Bonenta’s discovery originated from the analysis of decades of research describing the co-receptor regulation of growth proteins called growth factors (see DeCarlo & Whitelock, 2006 (PDF) and Ellis et al, 2010 (BioMed Central). If you think of hormones and growth factors as working like keys that turn on the healing in your cells, Bonenta’s important co-receptor is what is needed to make the key fit the lock allowing the lost bone to regenerate properly. As the complicated synthesis of this co-receptor would be dauntingly impractical for the manufacturing process, Bonenta predicted and proved that adding a DNA pro-drug for a small portion of the co-receptor would improve the dose-effectiveness of the bone growth factor BMP as a therapeutic. In two different models of bone synthesis – the first, healing of a bone wound, and the second, ridge augmentation requiring building bone on top of existing bone, – our hypothesis was confirmed (see DeCarlo et al Free PMC Article).

Clinical Proof to Date

To date, all of our data has been pre-clinical, meaning not yet in human patients. We had to use rodent studies, but all we did was place the Bonenta synthetic graft material right on top of their jaw bone (after a small incision to lift the gums) and waited a few weeks while new bone replaced the Bonenta implant material. Below are some pictures to demonstrate the striking differences in new bone made by placement of the Bonenta Cranial Bone Graft Implant compared to a standard graft material.

First, we see micro-computerized tomography, or CT scans. On the left jaw we placed a leading competitor bone graft, which is made from crystals of tricalcium phosphate (TCP) supplemented with bone growth hormone (BMP2). On the right jaw we placed Bonenta’s Bone Graft Implant, which we are calling B-247 in the laboratory. The left image is a 3-D reconstruction and the right is the x-ray view. The bone is white in the pictures. Clearly, the B-247 generated a fantastic amount of new bone on top of the ridge where it was placed, while the leading competitor generated no new bone. A close look shows the new bone from B-247 is integrated smoothly with the old bone of the jaw, and that it has a nice, healthy marrow.

This is depicted below in histological section (slide view), where the bone is blue. New bone generated from Bonenta’s B-247 implant after only 6 weeks healing (encircled) is integrated with the jaw bone (slanted lines) and the healthy marrow within the new bone (red) is evident.

Compared to another competitor, Medtronic’s InFuse product depicted on the left below, Bonenta’s Bone Graft Implant (right) generated significantly more new bone (encircled) on top of the jaw, shown at 12 weeks healing.

For those who appreciate statistics, below are charts depicting means and standard deviations of each treatment group, where the B-247 is compared to the InFuse competitor and the TCP condition with the bone growth hormone BMP2.

In our models, the following conclusions were drawn:

• Bonenta’s technology more than quadrupled (4-9 fold) the dose-effectiveness of BMP-2 osteogenic activity for in vivo de novo bone generation
• Bonenta’s new bone graft technology was greatly superior to various other bone graft products
• Bonenta’s new bone graft technology provided more than 5 times as much maxillary ridge augmentation than Medtronic’s InFuse™ using ≈1/30th of the BMP-2 dose
• Bonenta’s new bone graft technology generated new bone with 4 fold greater density than new bone generated by InFuse™
• Bonenta’s new Cranial Bone Graft Implant generated minimal inflammation and did not cause osteonecrosis in the first 3 weeks post-implant as did InFuse™
• Bonenta’s new Cranial Bone Graft Implant only generated new bone that was connected (contiguous) with the existing bone and only where the Implant material was placed

These data can be reviewed in detail at the following link (DeCarlo et al, www.ncbi.nlm.nih.gov/pubmed/22967000).

FDA Status

The FDA has designated the Bonenta Cranial Bone Graft Implant as a combination product, under the regulation of CBER (RFD110081). A request for FDA clearance has not been submitted by Bonenta, and your support will allow us to obtain that clearance and test the Cranial Bone Graft Implant in a human pilot trial.

How We Help Patients

Bonenta’s new bone graft implant will give trauma victims, and accident victims, and wounded servicemen, and children with developmental defects a product that can regrow missing or damaged bone of the skull (or elsewhere) rather than replace it with rods, plates, plastic or cement.

Patients present daily to hospitals around the world with head trauma or disease that requires a portion of the skull to be repaired. Currently, their choices for replacing the lost bone to a) protect the brain and b) provide an appropriate aesthetic result are limited. The Bonenta synthetic bone graft is being developed for patients as a preferable treatment alternative to recreate the form and function of the skull for a lifetime, eliminating the risks that come with cements, plastics, or plates.

While medicine and device technology has come a long way, to have a plate, or plug of plastic or cement to fill a bone wound in your head, or to leave it empty, cannot be considered ideal, for three reasons: first, plugs of plastic or cement cause irritation, inflammation, become surrounded by scar tissue, and can become loose and leak, leading to complications that effect the skull and brain; second, loose or empty holes in the skull can lead to direct damage of the brain; third, plates or plugs do not grow or change shape with the rest of your skull leading to leakage and deformity, and placing materials like plates or plugs is extremely problematic for our youth who will grow rapidly. Because these choices are so inadequate, clinicians often choose to do nothing, leaving the skull with a soft hole and an indentation. We can do better for our futures.

An alternative is to use bone obtained from another part of the body, such as the hip. However, this of limited supply, can be unpredictable and dissolve, and may result in long-term pain and problems at the site from where they take the bone (morbidity). Many patients suffer from arthritis and a limp when cores of bone are taken from the hip to be transplanted.

Too many of us or our beloved will need some bone repair of the head or elsewhere, so we want the technology to improve. Bonenta has advanced the science to where we can place an implant that will stimulate the body to replace it with their own bone. We offer this as the near future and as a much needed alternative to plates, plugs, and cements with all their potential complications.

How We Help Doctors

Bonenta’s Cranial Bone Graft Implant has advantages to the doctor that make it competitive and appealing:

• It is a single unit, single-phase device so it is simple to place, no mixing needed
• It can be cut and shaped to fit the defect unlike other bone grafts that typically are loose and must be poured or packed.
• It remains in place as a unit during the early stage of wound healing to minimize complication
• It is freeze-dried and stable for easy storage and handling
• It is highly osteogenic, moreso than any existing synthetic competitor and moreso than
  allograft bone, maximizing bone regeneration, clinical success, and patient satisfaction
• It slowly elutes the active components limiting their effective concentration to the device area providing a good safety margin unlike the current competitor.
• While not necessarily a competitive advantage, since other bone graft substitutes are reimbursable, a health care reimbursement precedent makes it appealing to both doctor and patient.

How We Help Hospitals, Institutions, and/ or Medical Facilities

We understand that in today’s medical environment new products are often approved and purchased by the hospitals or medical facilities, and that third-party reimbursement systems have an important role in this. Bonenta’s new Cranial Bone Graft Implant will be in the same class of biologically enhanced bone graft devices to allow reimbursement. There are four other strong reasons that institutional medical care organizations should prefer Bonenta’s Cranial Bone Graft Implant over any of the current accepted alternatives.

• First, biologically enhanced bone grafts have the potential to be significantly more effective than either the inert filler bone graft substitutes or the mostly inactivated human cadaver bone graft materials. There are concerns about transmissible diseases with cadaver bone and it is limited in supply. Primarily, though, the best outcome possible prevents subsequent complications and improves reputation.
• Second, the single piece, ease of use by the physician will favor efficiency over other bone graft alternatives.
• Third, the alternative option of using bone from another area of the body (autograft) comes with additional risk of complications, utilizes OR and recovery hours, and can lead to long term patient dissatisfaction with second-site morbidity.
• Fourth, the current biological bone graft alternative (InFuse) is very expensive, has significant, highly publicized, risks because of its high active component concentrations, and is not appropriate for cranial bone repair due to the lack of retention of active components. The Bonenta Cranial Bone Graft Implant is designed to overcome these risks with low doses of active components and high retention, thereby improving efficiency and outcomes for skull repair. Institutions may be favored by inclusion of Bonenta’s Cranial Bone Graft Implant.

How We Help Our Partners

We see the Bonenta Cranial Bone Graft Implant as relatively safe and highly profitable product adoption for either big Pharma or smaller device companies for the following reasons.

• First and foremost, the market for a biologically enhanced bone graft exists; Medtronic sells an estimated $700M of InFuse annually.
• Second, reimbursement pathways for this product class exist.
• Third, patents on the active component of InFuse end in 2014.
• Fourth, patents on Bonenta’s Co-activating biologic may be extended for up to 14 years post-approval.
• Fifth, the market leader, InFuse, has a poor risk/benefit margin because of poor design and lack of the patented Bonenta “secret sauce” so it will be easy to overtake with Bonenta’s Cranial Bone Graft Implant in orthopedic and spine applications following entry for cranial repair.
• Sixth, the CMC (manufacturing process) is relatively simple for Bonenta’s Cranial Bone Graft Implant.

How We Will Spend Your Contributions

• Task 1: dosing and toxicity data in a test model (swine) – the implant grows bone extremely well in the head of the rat but we need a 3 month test in a larger skull bone similar to the human.

What Will Happen in the Next Phase of Development

• Task 2: cGMP manufacturing – this means we get ready for human testing by assuring we have the systems in place to manufacture the implant to be sterile and consistent.
• Task 3: definitive GLP toxicity, toxicology, and biocompatibility data – this is the step where the FDA needs all the safety data for the final, finished product that will be used in the human trials.
• Task 4: IND allowance for human trials – this is what the FDA will issue to Bonenta once it is satisfied with Tasks 2 and 3.
• Task 5: Human Safety/Efficacy Trial: A single-dose open-label Phase I/IIa safety and efficacy trial with 12 patients-in-need to be treated with the Bonenta Cranial Implant. As this is a First-in-Human study and primarily a safety trial, only a single clinical trial site will be used. Patients who have been injured seriously in the skull will be recruited.

Who We Are

Bonenta’s corporate leader is Dr. Arthur DeCarlo (LinkedIn)

Scientifically we have had leadership from our Advisory Board of Dr. John Whitelock, currently Dean of Research in the Engineering School at The University of New South Wales, and Dr. Ling Li, currently a senior research scientist at Torrey Pines Institute for Molecular Studies (LinkedIn). Dr. Whitelock and Dr. DeCarlo are the inventors of the technology.

Regulatory leadership has come from Lindsay Donald, currently with Intertek Cantox (LinkedIn). Moving forward we have the added regulatory expertise of Dr. Suzanne Stratton (@SStrattonPhD).

Medical oversight is provided by Dr. DeCarlo, and Dr. Chambers has signed on to be the clinical investigator on the pilot clinical trial. Dr. Chambers is on staff at University of Alabama at Birmingham Dept. of Neurosurgery following residencies at the Johns Hopkins University and as Chief Resident at Vanderbilt. Dr. Chambers is also involved in research on brain cancer.

How to Find Us:

www.bonenta.com

Twitter: @arthurdecarlojr

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