Musculoskeletal tissue injuries and degeneration are common and debilitating for a high number of patients (Brooks, 2006). Unfortunately, endogenous musculoskeletal tissue regeneration is limited in many cases and may be affected by inflammation and the degree of damage. For example, most fractures of long bones heal spontaneously, whereas large segmental defects fail to heal. Additionally, although articular cartilage has almost no intrinsic reparative potential, tendons and ligaments may heal, but often with inferior properties. The high prevalence of these injuries has led to significant investment in the development of new therapies to enhance healing and augment current surgical interventions. Often the goal is to mimic and recapitulate the natural healing cascade and developmental process by transplantation of tissue-specific stromal and progenitor cells or by endogenous manipulation to enhance the native repair capacity of cells.
There has been a continuing increase in the number and type of stem and stromal cells being pursued in human clinical trials for treatment of musculoskeletal injuries (Steinert et al., 2012). Most approaches in this area are based on ex vivo-expanded mesenchymal stromal cells (MSCs) derived from bone marrow (BM). Originally identified and characterized by their multilineage differentiation potential in vitro, multipotent capabilities of MSCs in vivo have not been clearly demonstrated to date, particularly because of the lack of methods to identify and define differentiated populations (Nombela-Arrieta et al., 2011). Central to recent progress in the field has been the understanding that stem and progenitor functions of MSCs may not be the key attribute that mediates tissue repair. In addition, there is outstanding controversy over the terminology of exogenously supplied MSCs as stromal cells, and various terms, including medicinal signaling cells, have been proposed to more accurately reflect their therapeutic function in vivo (Caplan, 2017). Nevertheless, the therapeutic benefit of these cells has been largely explored. Significant advances have been made in developing strategies that deliver, protect, and recruit stem cells, and the bioengineering field is evolving to improve current surgical techniques.
This review first describes current treatments and reports the recent progress in clinical investigations of stem and stromal cell-based therapies for musculoskeletal repair with a particular focus on bone and fibrocartilaginous tissues. The current understanding of appropriate cell sources and delivery strategies is then illustrated toward endogenous repair of musculoskeletal tissues. Last, emerging therapeutic concepts are highlighted in the context of biomaterials as a particularly attractive tool to control stem and stromal cell behavior both ex vivo and in vivo, to recruit endogenous stem cells, and to control the local healing environment. Such approaches have great potential for future therapies in musculoskeletal repair.
The intrinsic repair of bone defects mirrors many events of embryonic development and makes fracture healing one of the rare postnatal processes that are regenerative and can ultimately restore damaged tissue to its pre-injury structure, composition, and biomechanical function (Figure 1). In spite of the unique capacity of bone to heal, a number of clinical indications remain where therapeutic intervention is required. In the case of complex trauma with multiple fractures, infections, and tumor-associated and endocrine diseases (e.g., diabetes, osteoporosis), the body’s natural healing response is impaired, and non-union can occur in up to 15% of cases (Grayson et al., 2015). Another debilitating disorder is non-traumatic avascular osteonecrosis, which can lead to collapse of the femoral head and accounts for 10,000–20,000 total hip replacement surgeries in the United States per year (Figure 1; Moya-Angeler et al., 2015). Autologous bone grafting represents the gold standard for management of bone defects and non-unions, and union rates of more than 90% have been reported using iliac crest bone. However, considerable donor site morbidity and limited volumes must be taken into consideration. Additionally, allogeneic or synthetic bone substitutes, such as ceramics, corals, or polymer-based materials, have not reached the biological and mechanical properties equivalent to autologous bone (Table 1).
In addition to direct traumatic injury, complex damage of bone tissue (e.g., open fractures, tumor ablations) often results in concomitant soft tissue injury, including adjacent muscles. Although skeletal muscle has the inherent ability to regenerate after injuries, the regenerative capacity fails when a large volume of muscle is lost (i.e., volumetric loss). Such severe injuries may lead to fibrosis, atrophy, and ischemia when left untreated, accounting for significant socioeconomic costs ($18.5 billion in healthcare costs are associated with sarcopenia alone) (Janssen et al., 2004). Therapeutic treatment options are limited to physical therapy, scar tissue debridement, and transfer of healthy, innervated, and vascularized autologous muscle tissue. However, the outcomes of surgical reconstructions often remain aesthetically and functionally deficient (Grogan et al., 2011; Table 1).
Articular Cartilage and Meniscus
In contrast to bone and skeletal muscle tissue, the poor intrinsic healing capacity of articular cartilage and meniscus tissue presents a major challenge in clinics. Lesions from injuries or degeneration often result in gradual tissue erosion, leading to impaired function of the affected joint and degenerative osteoarthritis (OA) (Figure 1). Patients with post-traumatic OA account for more than 10% of the 27 million adults in the United States that have a clinical diagnosis of OA (Johnson and Hunter, 2014). Commonly, the first-line treatment of articular injuries includes arthroscopic lavage, partial meniscectomy, and BM stimulation techniques to penetrate subchondral bone (Table 1). Microfracture has been considered the gold standard for stimulating endogenous repair; however, it often results in the formation of inferior fibrocartilaginous repair tissue. This cartilaginous tissue is vulnerable due to altered biomechanics of the subchondral bone, which raises concerns about the long-term efficacy of microfracture (Solheim et al., 2016). Therefore, secondary and more complex procedures strive to restore the hyaline cartilage, such as osteochondral autografting from the less weight-bearing periphery (mosaicplasty) and autologous chondrocyte implantation (ACI). ACI represents one of the first clinical applications of tissue engineering where a biopsy from a low-weight-bearing region is performed, and ex vivo-expanded chondrocytes are implanted in a second operation. The de-differentiation of monolayer expanded chondrocytes and potential of recovery when implanted has been a matter of debate, and matrix-based ACI techniques have been developed that use absorbable scaffolds (e.g., porcine collagen) to support the implanted cells (Makris et al., 2015). An important limitation of these techniques is the long recovery time (6–12 months) to ensure neotissue formation. The choice of articular injury treatment depends on several factors, including localization and size of the lesion, the level of activity, and the degree of associated damage of menisci and ligaments.
Tears of the fibrocartilaginous menisci require surgical intervention for nearly 1 million patients in the United States annually (Vrancken et al., 2013). For lesions located in the peripheral vascularized region of the meniscus, repair strategies such as sutures and anchors allow preservation of the meniscal tissue. However, meniscal lesions often appear in the avascular central regions, which makes them less suitable for healing and usually requires partial or (sub)total meniscectomy (Figure 1; Table 1). In some cases, further treatment with a meniscal substitute, such as an allograft or a synthetic implant, is indicated to limit OA (Vrancken et al., 2013).
Other Fibrous Musculoskeletal Tissues
Another large proportion of musculoskeletal injuries in the clinic is represented by other damaged fibrous structures, including tendons, ligaments, and the annulus fibrosus (AF). Often, degenerative pathology precedes acute trauma, and, like articular cartilage, these tissues have a limited healing capacity. One of the most common tendon injuries presented clinically is tearing of one or more of the interdigitating tendons of the rotator cuff (Figure 1). Failure of initial physical therapy or acute trauma in young patients motivates surgical repair using open or arthroscopic approaches for subacromial decompression, tendon debridement, and suture or anchor supplementation (Table 1). Still, repair is limited, particularly within the complex anatomic arrangement forming the shoulder cuff. The formation of fibrovascular scar tissue frequently leads to significant morbidity, re-ruptures, and difficulties in treatment choice.
The intervertebral discs (IVDs) are composed of the nucleus pulposus (NP), a hydrophilic proteoglycan-rich gelatinous core, surrounded by a dense fibrocartilage ring—the AF (Figure 1). The gradual progression of IVD degeneration and the extrusion of the NP through defects in the AF is a major cause for lower back pain, a leading cause of global disability (Sakai and Andersson, 2015). Available treatments are mostly symptomatic, and surgical treatments often resect the structural obstruction resulting from herniation or fuse motion segments (Table 1). However, the complex structural features of IVDs surrounded by neural elements and inflammation frequently cause a homeostatic imbalance favoring a catabolic response governed by the loss of the IVD structure, which is often followed by facet joint arthritis and vertebra deformation, canal stenosis, and even deformations. Most importantly, disc replacement with synthetic implants or fusion of the motion segment does not cure the underlying pathology of IVD degeneration (Sakai and Andersson, 2015).
According to many physicians, PRP (Platelet-Rich Plasma) has been a lifesaver for their practice, while others claimed that it helped them become passionate about medicine again. This is because not only is it 100% from the body of the patient themselves, but it is also natural and comes with pretty much no side effects. It can also be used to treat a plethora of medical ailments, to the point where no other treatment options come close.
Although the above are all fantastic and solid reasons for offering PRP therapies, there are also a couple other reasons as well.
For instance, it is extremely simple compared to other treatment options. For about 1000$ as an initial investment, you can get started with offering PRP. The equipment is relatively cheap, and it pays for itself over a relatively short amount of time.
It also is not just a passing trend, as it has been going popular for a long time and shows no signs of slowing down. The market for PRP therapies is expected to reach almost 500 million dollars within the next 10 years, or an annual growth rate of 12.5% since 2015.
Patient satisfaction is another reason. In certain situations, the satisfaction rate for patients have been as high as 95%. This shocks many of the patients, who believe, although justifiably, that they cannot reverse or halt their condition without side effects, down time, and invasive surgeries.
The time for you to start including PRP into your practice is now, while the supply is low but the demand is booming. There is still a lot more promise when it comes to PRP as well, including combining PRP with other treatments to increase efficacy. Since no standard has yet to be established, you may be starting these standards yourself.
It is vital that we get more doctors to utilize PRP therapy so that they can be a pioneer in this field. PRP can turn medicine on its head, and missing out should not be a smart option.
The best part about it, is that PRP can be utilized in almost every field and specialty, from sports medicine, to pain management, skin rejuvenation, hair care, and even urology. Most of the physicians who utilize this treatment also saw higher patient retention rates as well.
So is there a legitimate reason to not add PRP to your practice?
Despite being rather simple, PRP extraction has been shrouded with debate on the reliability of the methods for the past decade. We are going to help clear up the debate by providing information on choosing the best PRP kit.
Using a kit is in itself vital to the creation of PRP. While it is possible to draw blood into a test tube and put it through a centrifuge and claim it is PRP, it’s otherwise ineffective. This is what is known as “bloody PRP,” and it might hold 1.5x the amount of blood platelets if you’re lucky, but it will also contain a ton of red and white blood cells. Because of this, this ineffective form of PRP can potentially cause flare ups after injection.
However, if you use a kit, that concentration of platelets can be as high as 5-7 times the baseline.
What Makes A PRP Kit Good?
This concentration of 5-7 times is vital for PRP to work, and kits allow you to choose whether or not you want to keep in the red and white blood cells, or whether you don’t. Each one would work on different ailments. However, some commercial kits may not deliver what you may want in your PRP, so it is good to know the difference between the kits.
- Gel Separators
Gel separators is pretty much just a test tube with some gel on the bottom. This gel is able to separate the blood from the platelets due to osmosis. The main issue is that when the test tube goes through the centrifuge, most of the platelets will also be caught by the gel as well. This will wind up with 1.5 times concentration of platelets at most, but it does take out the white and red blood cells as well, so that’s a plus.
- Buffy Coat
The kits that allow you to see a buffy coat are most likely to give you concentrations of 5-7 times. A buffy coat is a thin layer that is formed between the blood and the plasma after being in a centrifuge. This is mainly just platelets and white blood cells, with plasma on top, and packed blood underneath.
After this, you have to be able to separate the bufy coat from the red blood cells without contamination. This will help you to get PRP with less than 10% red blood cells.
- Buffy Coat with a Double Spin
The third and final type utilize a buffy coat which is devoid of red blood cells. This is the best kit on the market, because what you do is after separating the PRP from the red blood cells, you spin it again to further get rid of the red blood cells and to concentrate the platelets even more. After this, all that is needed to do is to separate the buffy coat, and this is PRP.
The Biosafe Kit
Although there are many kits that create PRP, the Biosafe kit has to be the best on the market. This is because it give you full control over the end product. Using this machine, you wind up with 10cc of usable product, which you can then double spin for that 5-7 times concentration. You can also choose whether or not you want some red blood cells in the finished product as well.
What is Leukocyte-poor PRP?
Leukocytes are otherwise known as White Blood Cells, and some researchers believe that they can be detrimental to PRP therapy. While there is no consensus as of yet, it is believed by many that these blood cells may trigger an inflammatory response, and even prevent growth factors from creating new cells.
However, some researchers believe that white blood cells are vital to a beneficial response. They believe that without these cells, you will be left with a lot of scar tissue at the site of healing. This Leukocyte-rich PRP also tends to have much more growth factors as well.
If you want to try leukocyte-poor PRP, you will need a Leukocyte Reduction filter, also known as an LR filter. These filters use electrostatic attraction to separate the white blood cells from the rest of the PRP. Although some filters can get clogged, a CIF-LR filter will be able to prevent that and filter out 99.99% of white blood cells.
There Is Plenty Of Evidence To Back This Up
Many people are highly skeptical about PRP, and are willing to ignore it without tons of randomized double-blind studies. Ignoring that some of the things that they do in their practice is also not proven in this manner. Many refuse to even look at the evidence, including the long line of evidence since the 1970’s, ranging over 6000 scientific studies.
The best evidence is how much clients will pay for this despite not being covered by insurance. This shows without any doubt that something about this treatment must be working. As long as there are clients, Adimarket will be there to provide the equipment for practices.
Although the clinical demand for bioengineered blood vessels continues to rise, current options for vascular conduits remain limited. The synergistic combination of emerging advances in tissue fabrication and stem cell engineering promises new strategies for engineering autologous blood vessels that recapitulate not only the mechanical properties of native vessels but also their biological function. Here we explore recent bioengineering advances in creating functional blood macro and microvessels, particularly featuring stem cells as a seed source. We also highlight progress in integrating engineered vascular tissues with the host after implantation as well as the exciting pre-clinical and clinical applications of this technology.
Ischemic diseases, such as atherosclerotic cardiovascular disease (CVD), remain one of the leading causes of mortality and morbidity across the world (GBD 2015 Mortality and Causes of Death Collaborators, 2016, Mozaffarian et al., 2016). These diseases have resulted in an ever-persistent demand for vascular conduits to reconstruct or bypass vascular occlusions and aneurysms. Synthetic grafts for replacing occluded arterial vessels were first introduced in the 1950s following surgical complications associated with harvesting vessels, the frequent shortage of allogeneic grafts, and immunologic rejection of large animal-derived vessels. However, despite advances in pharmacology, materials science, and device fabrication, these synthetic vascular grafts have not significantly decreased the overall mortality and morbidity (Nugent and Edelman, 2003, Prabhakaran et al., 2017). Synthetic grafts continue to exhibit a number of shortcomings that have limited their impact. These shortcomings include low patency rates for small diameter vessels (< 6 mm in diameter), a lack of growth potential for the pediatric population necessitating repeated interventions, and the susceptibility to infection. In addition to grafting, vascular conduits are also needed for clinical situations such as hemodialysis, which involves large volumes of blood that must be withdrawn and circulated back into a patient several times a week for several hours.
In addition to large-scale vessel complications, ischemic diseases also arise at the microvasculature level (< 1 mm in diameter), where replacing upstream arteries would not address the reperfusion needs of downstream tissues (Hausenloy and Yellon, 2013, Krug et al., 1966). Microvascularization has proven to be a critical step during regeneration and wound healing, where the delay of wound perfusion (in diabetic patients, for example) significantly slows down the formation of the granulation tissue and can lead to severe infection and ulceration (Baltzis et al., 2014, Brem and Tomic-Canic, 2007, Randeria et al., 2015).
In order to design advanced grafts, it is important to take structural components of a blood vessel into consideration, as understanding these elements is required for rational biomaterial design and choosing an appropriate cell source. Many of the different blood vessel beds also share some common structural features. Arteries, veins, and capillaries have a tunica intima comprised of endothelial cells (EC), which regulate coagulation, confer selective permeability, and participate in immune cell trafficking (Herbert and Stainier, 2011, Potente et al., 2011). Arteries and veins are further bound by a second layer, the tunica media, which is composed of smooth muscle cells (SMC), collagen, elastin, and proteoglycans, conferring strength to the vessel and acting as effectors of vascular tone. Arterioles and venules, which are smaller caliber equivalents of arteries and veins, are comprised of only a few layers of SMCs, while capillaries, which are the smallest vessels in size, have pericytes abutting the single layer of ECs and basement membrane. Vascular tissue engineering has evolved to generate constructs that incorporate the functionality of these structural layers, withstand physiologic stresses inherent to the cardiovascular system, and promote integration in host tissue without mounting immunologic rejection (Chang and Niklason, 2017).
A suitable cell source is also critical to help impart structural stability and facilitate in vivo integration. Patient-derived autologous cells are one potential cell source that has garnered interest because of their potential to minimize graft rejection. However, isolating and expanding viable primary cells to a therapeutically relevant scale may be limited given that patients with advanced arterial disease likely have cells with reduced growth or regenerative potential. With the advancement of stem cell (SC) technology and gene editing tools such as CRISPR, autologous adult and induced pluripotent stem cells (iPSCs) are emerging as promising alternative sources of ECs and perivascular SMCs that can be incorporated into the engineered vasculature (Chan et al., 2017, Wang et al., 2017).
Importantly, a viable cell source alone is not sufficient for therapeutic efficacy. Although vascular cells can contribute paracrine factors and have regenerative capacity, merely delivering a dispersed mixture of ECs to the host tissue has shown limited success at forming vasculature or integrating with the host vasculature (Chen et al., 2010). Therefore, recent tissue engineering efforts have instead focused on recreating the architecture and the function of the vasculature in vitro before implantation, with the hypothesis that pre-vascularized grafts and tissues enhance integration with the host. In this review, we explore recent advances in fabricating blood vessels of various calibers, from individual arterial vessels to vascular beds comprised of microvessels, and how these efforts facilitate the integration of the implanted vasculature within a host. We also discuss the extent to which SC-derived ECs and SMCs have been incorporated into these engineered tissues.
The first reported successful clinical application of TEBV in patients was performed by Shin’oka et al., who implanted a biodegradable construct as a pulmonary conduit in a child with pulmonary atresia and single ventricle anatomy (Shin’oka et al., 2001). The construct was composed of a synthetic polymer mixture of L-lactide and e-caprolactone, and it was reinforced with PGA and seeded with autologous bone marrow-derived mesenchymal stem cells (BM-MSCs). The authors demonstrated patency and patient survival 7 months post-implant, and expanded their study to a series of 23 implanted TEBVs and 19 tissue patch repairs in pediatric patients (Hibino et al., 2010). They were noted to have no graft-related mortality, and four patients required interventions to relieve stenosis at a mean follow-up of 5.8 years. The first sheet-based technology to seed cultured autologous cells, developed by L’Heureux et al., was iterated by the group to induce cultured fibroblast cell sheet over a 10-week maturation period and produce tubules of endogenous ECM over a production time ranging between 6 and 9 months. They dehydrated and provided a living adventitial layer before seeding the constructs with ECs (L’Heureux et al., 2006). Their TEBV, named the Lifeline graft, was implanted in 9 of 10 enrolled patients with end-stage renal disease on hemodialysis and failing access grafts in a clinical trial. Six of the nine surviving patients had patent grafts at 6 months, while the remaining grafts failed due to thrombosis, rejection, and failure (McAllister et al., 2009). An attempt to create an “off the shelf” version of this graft in which pre-fabricated, frozen scaffolds were seeded with autologous endothelium prior to implantation led to 2 of the 3 implanted grafts failing due to stenosis, and one patient passed away due to graft infection (Benrashid et al., 2016).
Most recently, results were reported for the phase II trial of the decellularized engineered vessel Humacyte in end-stage renal disease patients surgically unsuitable for arterio-venous fistula creation (Lawson et al., 2016). This clinical scenario offers a relatively captive patient population in which graft complications are unlikely to be limb or life-threatening, and infectious and thrombotic event rates for traditional materials such as ePTFE are high (Haskal et al., 2010). The manufacturers seeded a 6mm PGA scaffold with SMCs from deceased organ and tissue donors and decellularized the scaffold following ECM production in an incubator coupled with a pulsatile pump prior to implantation. Humacyte demonstrated 63% primary patency at 6 months, 28% at 12 months, and 18% at 18 months post-implant in 60 patients. Ten grafts were abandoned. However, 12-month patency and mean procedure rate of 1.89 per patient-year to restore patency were comparable to PTFE grafts, while higher secondary patency rates were observed (89% versus 55%–65% at 1 year) (Huber et al., 2003, Lok et al., 2013). Although Humacyte revealed no immune sensitization and a lower infection rate than PTFEs (reported up to 12%) (Akoh and Patel, 2010), there remains much work to be done to improve primary patency and reduce the need for interventions.
Harnessing the regenerative functions reported in ECs derived from adult stem cells and iPSCs offers the promise of improving TEBV patency. Mcllhenny et al. generated ECs from adipose-derived stromal cells, transfected them with adenoviral vector carrying the endothelial nitric oxide synthase (eNOS) gene, and seeded the ECs onto decellularized human saphenous vein scaffolds (McIlhenny et al., 2015). They hypothesized that through inhibition of platelet aggregation and adhesion molecule expression, nitric oxide synthesis would prevent thrombotic occlusion in TEBV. Indeed, they reported patency with a non-thrombogenic surface 2 months post-implantation in rabbit aortas. While introducing additional complexities, engineering ECs and SMCs with other regenerative, anti-inflammatory, anti-thrombotic genes could perhaps bridge the functional difference between SC-derived cells and native primary cells.
Many clients are highly skeptical that their ailments can get better just by utilizing a few injections. Many clients may quit after a few sessions, but then return when they feel their ailments easing up. This is especially true when it comes to the practice of Rheumatology.
Rheumatology has benefited immensely from the use of PRP, otherwise known as Platelet-Rich Plasma. This is because not only is it simple to administer, but it works wonders for musculoskeletal conditions, such as joint issues, swelling, and bone issues.
If you are a Rheumatologist, you have probably used, or at least heard, of PRP therapy. This has helped many patients from having to go through surgery. However, over 27 million Americans in the osteoarthritis segment alone would have benefited more if their rheumatologist used PRP therapy.
Not All Treatments Are Successful, Here Is Why
Sometimes PRP can work, sometimes it may not, and this can differ even among the same person. However, there are some things you can do to prevent treatments from failing.
For PRP to work, the platelets present in the blood extracted has to be more concentrated than the baseline in the body. This can work by utilizing a PRP kit, which you can purchase at Adimarket. Using these kits, you can get a 5-8x the baseline, which works best for the treatments.
- White Blood Cells
PRP with white blood cells behave differently than those that do not have it. Most popular forms of PRP have these blood cells. There are three subgroups within this: Red Blood Cells, that don’t have platelets, Platelet Serum that has suspended platelets, and the Buffy Coat, which has both platelets as well as white blood cells. Adding in white blood cells can help speed up the healing process by removing bacteria and dead or dying cells.
- Using Anti-Coagulants
When making PRP, it is standard to use an anti-coagulant. This prevents the blood from clotting, but it does make the blood a little more acidic than usual. This can be detrimental on the growth factors, so adding a buffer before injection can be beneficial.
The Growth Factors Used
PRP heals wounds rather well due mostly to the growth factors that re found in blood platelets. By activating these platelets, the growth factors are able to be used by tissues and ligaments. Although the specifics are not well known, there is plenty of evidence that growth factors help with inflammation, remodeling, and even regenerating cells.
What is the clinical Evidence supporting PRP?
- PRP and Subacromial Tendonitis.
PRP has been shown to be effective in treating Subacromial Tendonitis in many studies. One study, headed by Dr. Turlough O’Donnell of the UPMC Beacon Hispital in Dublin Ireland, studied 102 patients treated with PRP while another 102 were treated with a 20mL solution of bupivacaine and 80 mgs of methylprednisolone.
After 12 months of follow-up, the PRP group were 16 times less likely to have to have invasive surgery as opposed to the other group.
This is often a chronic form of tendinopathy, and treatments are rarely effective. However, studies involving PRO have been promising. In one study, 19 patients who would otherwise have gotten surgery were given PRP treatment instead, and after 8 weeks, they saw a 60% improvement, and within two years, that number rose to 93%.
Another randomized double-blind study compared PRP with corticosteroids in 100 patients with chronic epicondylitis. The beneficial effects of PRP far outweighed the effects of the corticosteroids.
- Plantar Fasciitis
Otherwise known as Policeman’s Heel, plantar fasciitis is fairly common in the field of rheumatology. The main treatment to date would be to simply mask the symptoms by using corticosteroids. However, one study showed that PRP was much better than corticosteroids after a 3 month followup.
- Knee Osteoarthritis
PRP therapies for osteoarthritis of the knee have been studies intensively in the past few years. These studies have shown a lot of promise for this therapy. One systematic review showing a total of 1543 participants showed that PRP therapy fares better than hyaluronic acid when it comes to improving knee joint cartilage.
How PRP can Benefit Rheumatology
PRP is not just a passing trend, and is here to stay, and may be the most useful tool for rheumatologists. With no other treatments coming close to its safety, efficacy, or simplicity, It is a shame that it is not more common than it currently is. Since this therapy carries no risk, there is no reason to at to not at least give it a try.
Trying it is relatively inexpensive, and will pay for itself over time. Adimarket will be happy to supply you with kits, and even a standard lab centrifuge.
We need more rhumatologists to utilize PRP and help patients forgo intrusive surgeries. This will be beneficial for over 27 million Americans. Besides, since it is a new treatment option, getting into the field early will make you a pioneer in the field, which will benefit your practice immensely.
Thousands of skincare centers across the nation provide at the very least one kind of PRP treatment. However, most do not go any farther than micro-needling with a topical solution. This is mainly because it is far simpler than all other methods, and it is incredibly popular. However, it would make more sense to many practices who have invested in equipment for add in PRP injections as well.
PRP Is Growing Substantially
Regardless of what is being treated, the protocol for obtaining PRP is the same: You draw the blood, place it in the centrifuge, and then take out the PRP from the rest of the material. This simplicity can be combined with PRP’s vast usability to create significant and mindblowing advances in modern medicine.
This includes skincare as well, as the PRP that you get from patients can be used in a plethora of ways. Here are a couple of examples of what can be performed by dermatologists and plastic surgeons the world over.
- Skin Augmentation
Adding a topical solution of PRP ccombined with microneedling can help to regenerate dying skin cells, and makes skin feel soft. Although this will probably work for most clients, many might want more. For instance, if you want to plump up the face, injecting PRPinto the dermis can help provide both beauty, as well as a healing process.
Although if you want to create volume, you will need a filler. One way to do this is by using a Platelet-Poor Plasma filler, or PPP, which is often left over from the PRP process. You can also use Hyaluronic Adic. A combination of these with PRP have been known to provide wonderful results, with some clinicians boasting a 100% success rate.
- Vitiligo Correction
Many companies will shill out millions of dollars to find out how to turn defective cells healthy again. Many are looking into DNA Technology. However, simply utilizing PRPP may provide the same results. Some studies have shown that adding CO2 laser therapy for correcting vitiligo to a PRP treatment can increase it’s effectiveness by 4 times. This can also be beneficial in other areas, such as correcting wrinkles, and even acne scars. So combining PRP treatments are conventional therapies can boost the effects tremendously.
So if PRP can help boost the effects of lasers, it may be able to also boost the effects of other skin therapies as well. It seems like a great opportunity to continue doing the work that you do, but this time it is more effective due to a simple method. This is something that hundreds of skin care facilities are already providing for their clients.
- Hair Rejuvenation
Mesotherapy is a common treatment that utilizes microinjections that deliver a medication throughout the skin’s service. This prodecure has been able to provide great quality results by adding peptides and vitamins to the mix as well. However, one of the best ways that you can incorporate this into your practice is by using PRP therapy.
Mesotherapy can also be used to provide an even amount of PRP all over the body, including face, neck, hands, etc. This helps to rejuvenate the skin and reduce wrinkles, discoloration, and stretch marks. However, this works best when it comes to hair loss treatments. In fact, adding PRP with mesotherapy has exceeding the expectations that the industry has set.
This is why we think PRP therapy is something that every skincare clinic should offer. Since hair loss effects both men and women, it is important to try to work to make your treatments as effective as possible. Your patients will benefit from it and satisfaction will rise, is there any other reason to put it off?
“But I Never Heard Of Them!”
Some of these treatments and combinations are incredibly new, so new, that many might not have heard of them before. However, this is why signing up to use them as soon as possible is vital. This way, you can bee a step ahead of the competition when it comes to providing great services.
The demand for PRP is only growing over time, and the sooner you can get on board, the better off your practice will be. If you are interested in learning more about PRP therapy, or checking out our line of PRP equipment, you can do so by going to the Adimarket website and checking it out for yourself.
PRP provides more effective treatments for less time, less money, and more satisfaction. Tons off practices have been putting their trust in this treatment and have been reaping the benefits long term. PRP is here to stay, so are you ready to seize the potential of this great medical revolution?,
PRP is a powerful means of regenerating tissues, and has pretty a pretty large growth in popularity among patients, especially those who suffer from alopecia. This is despite the apparently lack of evidence that supposedly surrounds the treatment.
Is It A Lack Of Evidence Or Just A Lack Of Funding?The lack of widespread research may have more to do with funding than anything else. Many of the studies that are currently out there about PRP were unfunded, especially on the subject of Hair Regeneration. However, despite this lack of funding, the demand for PRP treatments for hair loss is growing at an unprecedented rate.
When it comes to PRP kits, there are three kinds to choose from. Ones that use gels, one that create a buffy coat, and one that creates a buffy coat utilizing a double spin. It is pretty unanimous that the last option creates the most reliable and concentrated form of PRP possible, at 5-7 times the baseline amount of platelets.
This concentration level also has the most nutrients which helps for the regeneration of blood vessels and stem cells. One commonly recommended tactic is to combine PRP hair regeneration with micro-needling with a topical layer of PRP. This may be beneficial in some cases.
Micro-needling is a way to create small amounts of trauma, which the body reacts to via a healing response. This response, mixed with PRP, can help to stimulate the growth of new cells.
In some instances, a dermatologist might have three sessions, with the first two being PRP injections, and the middle one being a micro-needling with a PRP topical solution. However, micro-needling is completely optional. Whether you choose to use this method or not, you will still be injecting the patient with PRP at the scalp.
Combining PRP with an Allograft Matrix
One thing that many hair regeneration experts do is combine PRP with an Allograft matrix. These are often used when healing wounds, as it changes inactive adult stem cells back into an active form. This makes the wounds heal faster.
This is because an allograft acts like a scaffold that proliferates cell regrowth and speeds up the healing process. Many experts in the fields have noted a high degree of success by using this method.
Allografts are generally made from using the bladder tissue of pigs. However, a better type of allograft is made from amniotic tissues and fluid. This type of allograft can be utilized with little or no chance of being rejected by the body, as opposed to those made from pig bladders.
Medications Vs PRP
The main drugs that are commonly used to regrow hair are Minoxidil and Finasteride. These were designed to be able to prevent male pattern hair loss, but did almost nothing when it came to regrowing lost hair. However, these drugs have been well known to only be temporary solutions, and if the patients stopped taking the drugs, the benefits of them would quickly reverse. These are also not 100% effective at stopping hair loss either, but it can slow the progression.
However, PRP is different. It may actually be the only treatment on the market that has been clinically proven to regrow hair and heal hair follicles. This means that it only only slows down hair loss, but actually helps with hair growth.
Many may ask how temporary the solution is, saying that the other drugs on the market are just temporary solutions. However, many pateints report that a PRP and allograft combination treatment was able to give them great results that lasted for nearly half a decade or more with just one treatment. However, each patient is indeed different.
Aside from drugs, we only had one other choice when it came to hair loss, and that was hair transplants. This is why PRP has been growing in popularity in hair regrowth groups lately. Although those other treatments are not obsolete in the slightest, adding PRP therapy can be both beneficial and safe to patients in the long run.
Some people combine the two, and use PRP alongside Minoxidil and Finasteride with little to no side effects seen to date. You can even combine PRP with laser light scalp stimulation therapy, but that is up to you.
So Try It Out
PRP for hair regeneration, skin rejuvination, and even facelifts is going strong with no sign of stopping. Many dermatologists have already taken the plunge, and since this treatment is not going anywhere anytime soon, it may behoove you to join in on it too.
For more information about PRP including equipment, check out the Adimarket website. We provide great tools for any practice to utilize.
When it comes to side effects, ease of preparation, fast treatment times, and cost, PRP is above them all in orthobiologics. However, aside from PRP, there is one other alternative that is showing promise: Amniotic Fluid.
Due to it being a really good source of regenerative material that is not only highly proliferative, but also that produces almost no immune response, Amniotic Fluid has been a popular substance to theorize about since the late 1930’s. That is not all though, as this fluid is also high in collagen, growth factors, and hyaluronic acids. These are found in high quantities, making them a good choice for promoting regeneration.
This fluid is also high in stem cells that contain B7H4, a substance that promotes wound healing and even shows promise as a way of growing functional blood vessels. This was demonstrated to be true by scientists at Rice University and Texas Children’s Hospital.
However, we are not going to talk about that kind of Amniotic fluid. The one that we are going to talk about has been frozen, thereby killing the stem cells. This is actually a good thing, as the FDA has banned the presence of stems cells in amniotic fluids.
How Allografts Of Amniotic Fluids are Created
Allografts (Grafts taken from someone besides the person receiving it) of Amniotic Fluids are like Platelet-Rich Plasma that is already ready to be injected. This way, you and your patients receive all of the benefits associated with PRP therapy, without having to extract it yourself.
This amniotic fluid is taken with consent from mothers who decided to donate this fluid during a c-section. Not only were the women themselves pre-screened, but the fluid is tested again afterwards, and then prepared to be instantly used for a wide watch of medical ailments.
The fact that Amniotic Fluid has very little effect on one’s immune system makes it a wonderful allograft. This means that the body is far less likely to attack the donor material, making it far less likely to be rejected. Also, much like PRP, they are also known to fight inflammation, and keep microbes at bay. They are also multipotent cells, meaning they can turn into any cell they need to, making them a gold standard for regenerative medicine.
Since Amniotic Fluid is not taken from the person it it being used on like PRP, it misses out on a lot of those benefits. However, the large amount of elastin, fibronectin, and collagen makes it a great substance to use in wound healing and cell regeneration. It also contains a ton of growth factors, including PDGF, EGF, VEGF, and FDF to name a few.
Amniotic Fluid Allograft
It is often used to improve chronic pain conditions, as well as sports injuries, arthritis, and potentially even the symptoms of aging. It can be used by doctors along with PRP therapy to increase the effectiveness of the therapy. It can also be combined with bone marrow aspirates or hyaluronic acid.
The Potentials Of This
Many doctors may not want to spend the time and money investing in PRP therapies, so we think that Amniotic Fluid in general, could be a wonderful alternative to PRP therapy. Also, this can also be used as a stepping stone to help providers that are new to regenerative medicine to potentially get to PRP or stem cells over time.
We are convinced that once you get started with regenerative medicine, whether it be Amniotic Fluids, PRP therapies, or stem cell therapy, you will prefer it over other invasive procedures for sports injuries, arthritis, and other wounds. This will help save at least a few patients from having to do any unnecessary surgical procedures.
Although they can perform surgeries, osteopathic physicians try to avoid doing so whenever possible. Because of this, PRP seems to be an excellent fit for their practice. Since Osteopathy was built on the idea of self-healing, PRP seems to be a perfect fit.
A little while ago, PRP research was reviewed by The Journal Of The American Osteopathic Association, and concluded that more studies and evidence would be needed to make a solid statement on it. A little while later, a case study was filed, showcasing an 18 year old high school football player who suffered from a sports injury. The case study showed that the muscle injury healed rapidly under the effect of PRP therapy. So although PRP is not constantly held up on a pedestal by the mainstream yet, does not mean that Osteopathic Physicians can’t learn a lot or benefit from the use of PRP in their practice.
How Osteopathic Physicians can Benefit From PRP
- It’s Holistic
Due to the fact that Osteopathic Physicians prefer to treat the patient, as opposed to just treating a disease or the symptoms, PRP is a great fit. It works by using the body’s own resources and mechanics and helps the body to heal itself over time. It works because, instead of simply dealing with symptoms, like many practices and conventional medicine does, it works to deal with the problem head on.
For instance, there are many examples of PRP therapy taking the place of surgery and medicine. Such as the cases where female patients were able to revive their sex drive, although they were initially treated for incontinence. So although PRP therapy was created and pushed by allopathic doctors at first, PRP works wonders in the field of Osteopathic medicine, and can become one of the best methods of treatment for Osteopathic physicians.
- Musculoskeletal Issues
In some practices, musculoskeletal pain can be something that Osteopathic Physicians deal with often. However, it is good to note that PRP is quickly becoming one of the main treatments for these kinds of issues. For instance, many researchers believe that PRP should be the main choice for people who suffer from knee meniscus.
In 2016, University of Missouri Doctor Patrick Smith published a FDA-sanctioned double-blind randomized placebo controlled clinical trial on PRP. These kinds of trials are considered the gold standard in research. The results of the study was that PRP provided safe and notable benefits for people who suffer from knee Osteoarthritis.
- PRP has a great deal of potential
The third and most important reason why all physicians, including Osteopathic Physicians, should start using PRP therapy is due to how wide its scope is. Due to the fact that PRP is simple and common, it is safe to say that if PRP can work on knee joints and tendons, that it most likely works on other tendons, joints, bones, and muscles as well. PRP will soon be a commonplace treatment when it comes to pretty much all musculoskeletal diseases.
This means that PRP has a near limitless potential. This is especially important for Osteopathic Physicians, as if there is a problem with the patients wrist, it could be that the main issue appears further down the arm. This is why multiple PRP injections on various areas of the arm can work to not just heal the issue, but also enhance the other traditional methods that are used. This will help restore the balance t the body, and give full functionality back to the patient.
American Academy of Regenerative Medicine Doctor Peter Lewis has administered over 100,000 PRP injections to over 12,000 patients. He claims that more than 80% of his patients who have gotten PRP therapy has had fantastic results. Even people who have claimed to need surgery could be benefited by the use of PRP.
Are They FDA Approved?
As of this year, PRP treatments are not yet subject to FDA approval. This is because all of the treatments are performed on the same day as the extraction, and uses only materials that are already inside the patients own body. Because of this, the PRP therapy is within the scope of the FDA Code of Federal Regulation title 21, part 1270, 1271.1. As a result, it is exempt from needing approval.
How does the U.S. FDA regulate cell therapies? (351 vs 361 Products)
In the United States, cellular therapies are regulated by the FDA’s Office of Cellular, Tissue, and Gene Therapies (OCTGT) within the FDA Center for Biologics Evaluation and Research (CBER).
According to the FDA, the Center for Biologics Evaluation and Research (CBER) regulates:
Human gene therapy products
Certain devices related to cell and gene therapy
CBER uses both the Public Health Service Act and the Federal Food Drug and Cosmetic Act as enabling statutes for oversight.
In the U.S., human tissues intended for transplantation are regulated by the FDA as “Human cells, tissues and cellular and tissue-based products” or “HCT/Ps.” Under U.S. law, any company that engages in the collection, processing, storage, screening/testing, packaging, or distribution of HCT/Ps must register with the FDA.
351 vs. 361 Products
Currently, the FDA’s Center for Biologics Evaluation and Research (CBER) is responsible for regulating HCT/Ps and it has two different paths for cell therapies that it constructed to reflect what it considers to be “relative risk”. These pathways are commonly called “361” and “351” products.
Cell therapies can potentially be regulated under either pathway, as described below:
361 products that meet all the criteria outlined in 21 CFR 1271.10(a) are regulated as HCT/Ps and are not required to be licensed or approved by the FDA. These products are called “361 products,” because they are regulated under Section 361 of the Public Health Service (PHS) Act.
In contrast, if a cell therapy product does not meet all the criteria outlined in 21 CFR 1271.10(a)), then it is regulated as a “drug, device, or biological product” under the Federal Food, Drug, and Cosmetic Act (FDCA) and Section 351 of the PHS Act. These 351 products require clinical trials to demonstrate safety and efficacy in a process that is nearly identical to that what is required for pharmaceutical products to enter the marketplace.