All good. All right, thanks to everyone who was here today to learn a little bit about Axogen. Just before I get started, I just want to draw everyone's attention to our forward looking statements. You're familiar with these and we will certainly be making forward looking statements, but we may or may not be updating these on a regular basis. A little bit about me. My name is Mike Dale. I've been, as you can tell by my gray hair, around for a little while and I've been more than 40 years in MedTech and as a CEO since the early 2000s. I've always made my decisions based upon whether or not the things I engage in provide a and present a credible clinical problem that justifies the time and the energies and all the resources that go into developing a company.
Secondly, whether or not that technology or that particular problem, whether or not you have a technology that in a distinctive way based upon benefit versus risk, can solve that problem, when you do, while it sounds very simple, you have the opportunity to build a great business and solve great problems and as such, probably a good vehicle for all stakeholders. I joined Axogen a little more than nine months ago because I believe that in that case, Axogen represented a solution that was both a genuinely credible clinical problem that was in need of solutions, and then finally that we had products that could solve those problems in a distinctive way.
What I'd like to do today is spend my time with you explaining to you some of the high level strategic assumptions underlying our recent strategic plan that we presented publicly, our progress to that plan, and our guidance for the near term with regards to the profile of the business for investors. First of all, what is Axogen all about? Our business purpose is focused on making and establishing an expectation to treat nerve defects in every clinical situation. Today, that is not the case. What are peripheral nerves? What function do they serve? Peripheral nerve function is something we all take for granted until we can't.
In this particular situation, the GIF that you see right here, the mother, her motor function in terms of being able to push the bicycle, the child, that's all completely dependent upon healthy functional nerve function. Feeling the sun in their faces is only possible because of the peripheral nerves within their face functioning normally, allowing them to feel changes in temperature. Virtually everything that we do every day, from swallowing, from tasting, and all elements of motor function are dependent upon healthy peripheral nerve function. This is indeed something from a health standpoint that's important to all of us. Axogen is unique in that we are literally the leaders in developing an entire focus area on providing the tools and the products that are necessary to ameliorate these problems when they present either through trauma or because of disease.
I'd like to tell you a little bit more about that. How big is this opportunity? How often do these problems occur? It's very large, as market opportunities go, based upon incidence rate and both trauma as well as presentation of disease. In the United States alone, we estimate that the market opportunity is more than $5 billion and it's equally as large outside the United States, although at present more than 95% of our entire revenue and activities are domestically focused. Towards the end of this year and beginning in 2006 and thereafter, we will begin to develop in more earnest an international presence to bring these same products and solutions. One of the key things here is that these markets, while we've been active in these markets doing work, are still very underpenetrated in terms of both awareness and actual clinical activity.
Therein lies the opportunity going forward, which we'll talk about. First of all, what are common nerve injuries? As you might guess, trauma, cuts, lacerations. These situations are one of the things that we probably think about if you were to think about a potential nerve injury because of the damage that can happen to an extremity or other part of the body. There are also iatrogenic injuries. Other surgical procedures, anytime you're cutting through the skin, you're cutting peripheral nerves. Depending upon that situation, you leave that patient with a deficit. There are also oncological presentations and other peripheral related diseases such as diabetes, for example. All these things can ultimately affect nerve function through either direct transection, stretching, contusions, pressures, and also amputation where a limb is removed.
Unless that nerve is capped in a proper way, that patient can develop a neuroma, which can lead to chronic continuous pain, which can range in terms of problem from one of simply bothersome to absolute debilitation. Lots of opportunities to do better for patients on our products and portfolio. We'll talk about those. What are those solutions? In green is Avance. Avance is the foundation that the Axogen home is built around. What is Avance? Avance is what's referred to as an allograft. This is basically donated human tissue that has been processed in such a way that makes it safe for reimplantation without an immunological response. However, Avance is unique as allografts go insofar as it's still bioactive. We retain a substance called laminin, which is a protein which acts as a signal to guide axonal regeneration.
The nerve itself is a physical scaffold. It's a human nerve. The actual structure and containment that you anastomose the allograft to the patient's nerve ending is similar. We're able to match these in terms of size and length. What makes it particularly special is not just that we have the physical scaffold, but we have the laminin to help guide that axonal regeneration. Therein lies the foundation for the allograft we call Avance. Complementing that is what we have and refer to as the algorithm. When you make these connections of an allograft to another nerve, or even in the absence of using Avance, maybe in this transaction, we have a subject, simple nerve reconnection. You need to complement that connection so that it's steady, so it can allow for that regrowth and that regeneration.
We use things like connectors sometimes in procedures. You have a lot going on. There are metal plates that have been put in as part of the traumatic surgical intervention, and the nerves might be laying over these, and you do not want those to be abraded or irritated. We use protection wraps to help avoid that. There are lots of different things that need to go in to ensure that you give the best chance for nerve regeneration. Axogen leads the way in developing the solutions in both surgical technique as well as the products necessary to support that kind of outcome. Why us? Why are we positioned here to win, to use that common phrase that anyone like myself would stand up and say, what is my right to win?
We've been at this for a while, and while the market is underpenetrated, we've been working for many years to develop the techniques and the software to underlie our rationale, including the clinical studies. Our RANGER study, which is our principal level one evidence study, we just published about two years ago, and we have been now organizing the company to go forward and to fully develop these opportunities we've worked so many years on. There's more than 100,000 patients have been treated with our product. Our benefit to risk profile, which is what every single solitary health medtech product is ultimately evaluated upon, is profoundly positive. We introduce essentially no risk, but offer the potential for great benefit. As a salesman, I can tell you that's something you can't always say to your customer. And we can literally say that.
To that end, we're well positioned to go forward. We have a foundation to build upon and we are genuinely appreciated as a trusted partner committed to good science. The priorities that we have organized ourselves around with the delivery and presentation publicly in March of our new strategic plan are these four clinical application areas. They're all based upon Avance. Trauma extremities is our first. Why is that still a priority? That's what the company was built around and we have our largest commercial footprint and our largest scientific database to build upon. That remains a priority for our business. The other segments that are listed here are all adjacencies and or new clinical pathways where the benefit to risk proposition and the logistics associated with identifying the customers and the service providers are favorable to Axogen.
While there are many others, these represent the priorities that we have selected for now to develop going forward. Let's talk a little bit about those extremities. Why are we here? Very large incidence rate on an annual basis in the United S tates alone, not to mention around the world, where trauma is incurred and the opportunity to restore that patient's function along with treating the other elements, broken bones, vascular injuries and so on, create an opportunity for nerve repair. We have the largest body of physicians that are trained. We are partners in training all new fellows coming out of training in all the medical institutions in the United States. The penetration level still remains very modest. As such, it represents a marketplace that we still have opportunity to add value.
The business is presently growing at double digits and we think this can continue over the course of the strategic plan period. Oral, maxillofacial and head and neck. This is a very much smaller universe of actual physician practitioners and service providers. These are very technically very complex procedures involving head and neck. Your head and neck, as you might guess, is proliferated with a huge peripheral nerve network. Every time these procedures are done, there is damage to peripheral nerves. There is an opportunity for us, based upon Avance in particular, as well as our other products, to help complement these procedures as they treat these patients in these types of situations where we can restore their quality of life and reduce the morbidity associated with these procedures. It is one of our fastest growing new areas of development.
We're very excited about the future here and we have thus made this a priority for development. Our next area moves into oncological space. This is breast resensation. It's a procedure and a technique that we pioneered and developed. We have been working on this for several years and have now decided to double the current sales group, which is a very small team of 12, to more than 24. We will probably continue to be expanding this group all into the over the strategic plan, period. Why is this a problem? Breast cancer is a continually growing presenting incident rate in the United States. What a lot of people do not realize as well, aesthetic reconstruction has advanced and come a long way post that when you do these procedures and remove this tissue, the woman's chest is essentially numb. There is no feeling here.
As you can imagine, from a quality of life standpoint, that's a difficult element to grasp and to appreciate. A lot of women are even unaware that that's one of the side effects that come from this. As part of the women's healthcare reconstruction act, one of the expectations is that the patient and the family and the physician have the right to discuss and to decide what their reconstruction journey should be for them. Given that we provide a nerve allograft that allows for regeneration and construction, what we are doing is we're pioneering the techniques to teach people how to remove the breast tissue by leaving the opportunity to regraft. Then we teach people how to do the regrafting. We train the surgeon pairs, both on the reconstructive side as well as oncological side, how to do these procedures.
It's a very rewarding marketplace. The feedback that you get, as you might imagine, when you're able to give people some level of sensation restoration is profoundly rewarding. We expect this market to continue to grow in high double digits for years to come. We're very small in terms of penetration levels and sites developed. Therein lies the reason for the investments in this space. Prostate, similar situation. Why are we here? While prostatectomy by robot has come a long way, and it's the primary means by which most of these cancers are intervened with, the dysfunction that accompanies these procedures still remains very high. There's almost universal recognition that the problem has not been solved. While we try to spare the nerves, we're not oftentimes successful. What's the opportunity? Very simply, a nerve is a nerve is a nerve.
If you can regraft, once you remove those tissues, an advanced allograft, you have the opportunity for that allograft to regenerate and therefore mitigating the dysfunction that accompanies these types of procedures. This is our newest application area that we're working on in terms of developing the protocols that are necessary to train for this. We have high expectations for this over the next four years as we continue that process. What this represents, therefore, is our strategic plan in terms of the areas of basic focus. There's nothing esoteric about this. These are all focused on areas of market development that come along with any novelty. The reason why we have guided over the course of our strategic plan period 15%-20% is based upon the present growth even before we initiate these activities.
As we expand the commercial footprint, as we continue to develop our level one evidence, as we focus on societal associations and development for creating care guidelines, and as we continue to invest in innovation, we believe that these particular opportunities are all eminently developable and will further enhance both the purpose of the business and then finally Axogen as an investment vehicle. One of the elements, given that continuing to invest in new products is one of our objectives, is that Axogen is special because of innovation, that's Avance. Avance is just one opportunity among many that we believe still exist. We will continue to invest both in the product side, one, enhancing regeneration through intrinsic improvements and Avance in the future and or complementary products and form factor that would further enhance regeneration. Those projects are underway. We're funding them as we speak.
Next, easy coaptation so we can talk all about this and all what's possible. It's all true. Technically these are not easy procedures. The more we can make these procedures simple, the more and the greater adoption that can transpire. We're working on that. Finally, with regards to protection, there's a lot of complementary procedures going on. When you do these anastomoses, you want to protect that work that you've just done. Our wraps and our protection devices are essential for that. Next is evidence. Claims are great. Evidence to support those claims is even better. These are projects that typically take three to five years to complete when you get to publication.
We are committed strategically, just as I have throughout my entire career of making sure that we complement and invest accordingly in developing the evidence and the things that we believe in. These projects that are underway today are just part of them. We have a number of level one evidence efforts that are planned that will commence as soon as we complete our transition to a biological license approved product, which is expected in September. What I'd like to do now is talk a little bit about the finances. Why do we believe some of these things are possible? What's different today than maybe three or four years ago? Here's part of the reason. Drawing your attention to accelerating growth, this business has continued to enjoy good growth. What are the basic reasons?
Good focus on science partnership and these are highly underpenetrated areas and this is worth talking about. That investment has also allowed us to reach a classic point of equilibrium and then scale and now leverage such that we are enjoying the benefits of that in terms of now contributing to positive cash flow. In addition, one of the key things that has contributed, consumed a great deal of time and cash in recent years has been the development of a new manufacturing facility to support the Biological License Application approval. Those are capital expenditures, huge cash consumers, has been completed and so those monies are now available for other parts of the business. As you can see in 2024 we moved to positive cash flow and we predict and expect that that will absolutely continue into the future and allow us to fund our entire strategic plan.
Therefore, our guidance we provided people is 15%-20% over the next four to five years. We continue to expect gross margins to incrementally improve over that period of time once we have one quality system that we can work upon as opposed to two, which is our current environment. Finally, the ability to self-fund all of the activities in house. A little bit about the growth. One of the questions we constantly get is, as you might have guessed, are you sure you guys can grow? Are you sure you can grow? You can see what we've grown 2022 to 2024. We believe there's no reason this business can't support that for the reasons I've already described. Dramatic under penetration. We're expanding the commercial teams. We're completely committed to classic market development exercises.
Finally, we're adding new clinical application areas for development which will further leverage this opportunity. Our financial guidance for the year was 15%-17%. We are on track as of Q1. Our gross margin we've guided based upon the transition to the BLA to be a little bit lower this year and noisy, 73%-75%. It has certainly started out that way. We did have one miss in Q1. These are episodic and we believe transitory. We still maintain our gross margin guidance for the year and that will ultimately exit the year at around 75%. In operational cash flow, we consumed $11 million in Q1. This is fully expected and consistent with prior history. Why? This is national sales meetings and payout of annual bonuses to employees based upon the performance of the company.
Going forward each quarter will be net cash flow positive, our measurements of success. We published secondary strategic plans so that people can kind of watch and ask questions as we report quarter to quarter. I'm not going to go through all the elements of the slide, but these are available publicly online on the website along with the rest of the strategic plan in detail. The takeaway that I would ask investors to note is that we are on track. The things that we said that we do, we're doing. The business is growing in double digits across the entire portfolio and we expect that to continue. Our high potential accounts, which is the primary target customers that we have decided to develop and concentrate our resources upon, has improved productivity and we have more of them than we have in the past.
We will continue to add to those professional education, which is key. It's all about training people to do the things that we believe need to be done. Those are on track and that's an expansion of our prior year's activities. Finally, from a market development standpoint, we've had just eight new publications added to the clinical compendium just this quarter alone. The takeaway from all of this is that the benefit risk proposition is broad, it's transparent, both on a controlled as well as contemporary publication standpoint, and remains very positive. With that, thank you for your time. I look forward to those who are interested. Continue to watch us. If you have any questions, we look forward to answering those in the future. I'd also like to introduce Lindsey Hartley.
Lindsey has recently joined the team and taken on the position of Chief Financial Officer for Axogen. So thank you again.