Regenerative Treatments in Sports Injury Medicine
Updated: Apr 21, 2020
Due to the vast amount of benefit, sports and exercise is recommended for all people, ranging from athletes performing at the highest level, recreational adults, the adolescent population, to people of advancing age. We know that taking part in sports can offer many health benefits, but it can also expose us to the risk of injury. Often what we see, other than direct trauma, is with advancing ages comes overuse injuries and degenerative joint diseases which impair functional movement and hinder taking advantage of exercise benefits.
Much attention is also focused on the long-term repercussions of sports injuries. Indirect joint trauma increases with various sporting activities, with meniscal (knee cartilage) or anterior cruciate ligament (ACL) injuries of the knee being prevalent. With this, it is thought that 1 in every 3/4 patients who return to play suffer a second ACL injury within 24 months, thus having huge impacts on progressing in elite sports. Furthermore, data is demonstrating that the long-term implications of ACL and meniscal injuries are significantly associated with increased cartilage damage over time, producing a 10-fold increase in the odds of total knee replacement in later years. Based on this, it is hugely important that structured injury preventative and reoccurrence programs are in place to a help reduce re-injury and to preserve joint cartilage health. Furthermore, to reduce the impact of overuse issues and post-traumatic degenerative conditions. Recently attention has been placed on treatments in regenerative medicine to assist in the matter. Regenerative therapies include platelet-rich plasma (PRP) and other blood-derived proteins, mesenchymal stem cells (MSC) and placenta products. The use of these regenerative treatments in sports injury medicine has exploded in efforts to facilitate healing and promote recovery of many sports-related injuries including ligament and tendon injuries, overuse injuries, cartilage damage, and degenerative conditions.
COMPLEXITY OF SPORTS INJURIES
Many different risk factors can lead to or contribute to sports injuries. Most common sports injuries involve chondral (cartilage) defects in the knee and ankle, in addition to overuse conditions like tendinitis. Often these conditions are predisposed by imbalances and altered mechanical load - giving off damage with a reduced ability of the tissue to repair. Unfortunately, over some time, overuse injuries can reach a period of tissue degeneration, which are much harder to treat.
Sports injuries are often dedicated to the sporting activity. Runners and track and field athletes often suffer injuries of the lower leg, i.e. knee joint, Achilles tendon, ankle, or foot. Whereas lower back issues are most commonly associated with golf, followed by elbow and shoulder injuries. Poor form and mechanics are responsible for the most common causes of injuries.
Therapeutic treatments range from physical rehabilitation, manual therapy, injections, to surgery, and are often set out by the requirements of the individual. Regenerative treatments aim to facilitate repair and recovery and to provide new tissue growth, without the effect of damaging side effects of particular interventions.
REGENERATIVE TREATMENT OPTIONS IN SPORTS INJURIES
The main regenerative options in the context of musculoskeletal injuries are often referenced to as 'ortho-biologics'. This article will focus on cell therapies and blood-derived treatments.
One of the main reasons for chronic injury is that musculoskeletal tissues have reduced regenerative capacity due to having an inadequate blood supply. Cell therapies aim to transplant living cells to promote new tissue, which is of huge importance in sports, to deal with the ongoing load. Autologous chondrocyte implantation (ACI) and autologous tenocyte implantation methods currently under investigation.
Stem cell treatment
Initially, the goal of stem cell-based therapies was to promote implanted cells to differentiate into tissue-specific cells. It is thought that stem cell therapies can assist in tissue regeneration. Bone marrow aspirate consists of harvesting bone marrow from the pelvic bone and has been the choice in most cell interventions for cartilage injuries.
Platelet-rich plasma (PRP)
The most popular blood-derived regenerative treatment is platelet-rich plasma (PRP). PRP treatment first being introduced into sports medicine and elite sports at the beginning of 2000. PRP treatment in sports medicine was aimed to facilitate recovery and decrease the time to return to competition. However, there still remains many different forms and protocols for the preparation of PRP which can alter delivery and success, mainly pure PRP, leukocyte-rich PRP (L-PRP), and newly promoted platelet-rich Fibrin (PRF). PRP is still a very favourable treatment, and further classification systems for PRPs in sports medicine have been proposed. Preclinical research supports the efficacy of PRP treatments in many tissues, especially tendon and articular conditions based on the anti-inflammatory and anti-catabolic (reduced tissue breakdown) effect of these therapies. Further injectable treatments have been introduced but have not been extensively investigated, such as autologous protein solutions, such as APS (Zimmer Biomet).
SPORTS INJURIES - TENDON INJURIES
When a tendon is subjected to repetitive load, it is always possible for the tendon to become overloaded and irritated, which can lead to inflammation and pain. Generally speaking with the correct attention and adaptations, this can be resolved fast. On the other hand, if this is subjected to continuous load and inflammation - this can result in chronic degradation and derangement of the tissue (tendinopathy). The most common overuse tendon injuries of the upper body include shoulder rotator cuff and the elbow tendons. The lower body tendons include the patellar (knee cap tendon), the Achilles tendon and the hamstring tendons, with the inclusion of plantar fasciitis. Currently, there are minimal clinical trials examining the efficacy of stem cell therapies for the above tendinopathies. However, there is high amounts of evidence to support the use of PRP treatment.
A common heel associated pain, common with runners. Achilles tendinopathy injection treatment with stromal vascular fraction (SVF) has been compared previously with PRP treatment in a study involving a total of 44 patients with a 6-month follow-up. Both treatments produced good clinical outcomes, with PRP showing superiority. Of recent years there has been much debate on whether PRP should or should not contain leucocytes due to their inflammatory properties. However, new research is identifying the important role of leucocyte rich PRP (L-PRP). A recent study by Hanisch and Wedderkopp (2019) looked at PRP treatment for Achilles tendinopathy, also assessing the difference clinical outcomes between leucocyte rich PRP and leucocyte poor PRP. They found that PRP is a promising treatment for chronic Achilles tendinopathy. Patients receiving PRP had an 81% probability of achieving an changes in pain intensity at rest and 61% probability of achieving during activity. Adding there were no significant differences in pain intensity or changes In severity between patients treated with leucocyte rich PRP or leucocyte poor PRP. Further high participant trials are needed to gain further knowledge.
A common knee tendinitis, prevalent in explosive movements. Still, there has only been a small number of trials completed looking at PRP treatment for patella tendinitis so, this area remains to be explored. A meta analysis of the available trials in 2017 by Dupley et al., from the department of trauma and orthopaedics in Preston UK reported that PRP injection treatment is statistically better than examined control groups, with follow ups suggesting that PRP is an effective and worthwhile treatment for patellar tendonitis.
Plantar fasciitis is a common overuse injury of the foot, highly associated with runners. Data analysis from various trials looking at the effectiveness of PRP treatment for plantar fasciitis, along with comparing PRP versus corticosteroid injection, identify statistically significant improvements in pain reduction and functional scores after 4 or 12 weeks. Furthermore, PRP treatment has identified better efficacy than the steroid treatment for long term success. Gonnade et al., (2019) looked at the regenerative efficacy of therapeutic quality platelet-rich plasma for plantar fasciitis and concluded that PRP has a regenerative effect with long and better efficacy in pain management of chronic recalcitrant plantar fasciitis.
Park et al., (2019) carried out a study on 56 patients to assess the effectiveness of pain relief in patients with grade 2 proximal hamstring injury, treated with platelet-rich plasma (PRP) or corticosteroid injection. At 1 week post-injection follow-up, 23 patients (71.9%) from the PRP group and 11 patients (45.8%) from the steroid group showed a positive response. After controlling for age, pre-procedure pain level, and gender, the positive response rate in the PRP group was higher than the steroid group. At 4 weeks post treatment, 23 patients (71.9%) from the PRP group and 13 patients (54.2%) from the steroid group showed positive response with no statistical significance. They concluded that the PRP group had shown a good clinical outcome and more favourable response compared to steroid group at 1 week and 4 weeks post-injection, which suggests that PRP therapy can be considered as a conservative treatment choice for grade 2 proximal hamstring injuries with better short-term and long term pain relief.
Commonly know as golfer/tennis elbow. Many treatment trials are available identifying the success of PRP treatment for elbow tendinopathy. However, limited trials are examining the efficacy of stem cell treatments. Also, in a comparison between PRP and corticosteroid, in 8 studies, both treatment options have identified pain reduction in the short term (2–4 weeks). PRP was superior again to steroid injection treatment at 6 months and 1 year, respectively. Thus, identifying increased tendon repair. These results confirm previous network meta-analysis comparing PRP, autologous whole blood and corticosteroid.
Shoulder rotator cuff tendinitis
Conservative management of shoulder rotator cuff injuries with stem cell therapies is again unexplored and very limited. A recent 2019 study examining the enhancement of tendon-bone healing after cuff injuries using a combination of stem cells and PRP which expressed good results. The current evidence for PRP treatment alone for shoulder tendonitis is very valued, particularly long term. Data from the journal of musculoskeletal medicine (2019) evaluated the efficiency of PRP to corticosteroid in cuff tendons, and observed long term well being with PRP, with improved function and quality of life, along with data identifying successful outcomes in mild rotator cuff tears. The association of PRP to rotator cuff surgery has also reported many benefits. Moreover, post-operative injections of PRP for reduced re-tear rates. A meta analysis looking by Wang et al (2019) looked at clinical efficacy and safety of PRP in arthroscopic full-thickness rotator cuff repair identifying that PRP injection can effectively improve the short-term outcomes following surgery of full-thickness rotator cuff tears, thus reducing the rate of re-tears, alleviating pain, and improving patients' shoulder function. Therefore, PRP injection can be recommended as an adjuvant therapy in single-row repair for improved short-term results. Chen et al., (2019) looked at the use of PRP in cuff tears which concluded that long term re-tear rates were significantly decreased in patients who had received PRP treatment. Again, Han et al., (2019) reported in their systematic review and meta-analysis revealing that PRP treatment with arthroscopic repair of rotator cuff tears decreases the re-tear rate and improves the clinical outcomes. It is very important to understand the differences between shoulder rotator cuff tendinitis/bursitis and tendinosis. Shoulder tendinitis can develop acutely as the tendon can become impinged with repetitive shoulder movements. As mentioned above, over a period of time chronic levels of inflammation can lead to chronic degradation of the tendon which is known as tendinosis. This differs from a cuff tear, but both can also happen simultaneously. Cuff tears often occur from a degenerative process over time. This is due to supraspinatous muscle having a strict blood supply that can often become compromised, leading to degradation of the muscle and tears. Again, due to this poor blood supply, this then can hinder the natural repair of muscle, which is why large rotor cuff tear often need surgical intervention, to attached the muscle back onto the bone.
3 recent meta-analyses have gathered all tendon conditions together and analysed whether or not PRP decreases pain and improves function. Fitzpatrick et al (2017) examined 18 randomised controlled trials with a total of 1066 patients, including PRP, PPP, autologous blood, and autologous conditioned plasma (ACP) injections and concluded that a single injection of L-PRP is effective in reducing pain. Chen et al. (2018) gathered data from 21 randomised control trial is with a total 1031 participants - which identified long-term follow-up results showing significantly less pain in the PRP group compared with the control group. Miller et al. (2017) included 16 randomised control trial is with a minimum follow-up of 3 months, Identifying that PRP was more effective than controls in reducing pain. Overall, meta-analyses evaluating only PRP injections favour the use of PRP to reduce pain and enhance function.
Steroid Usage for Tendinitis
Tendon injuries and disorders are a source of major concern in competitive and recreational athletes and in many working conditions requiring repetitive movements. Corticosteroid injections are a commonly used treatment for acute and chronic tendon disorders but unfortunately can carry unwanted side effects. Despite their popularity for being a good anti-inflammatory agent in the short term, the biologic basis of their effect and the systematic evidence for their benefits is largely lacking. In addition to suppressing local inflammation, corticosteroid injections can weaken tendons by inhibiting the production of collagen. Although some evidence exists for the treatment of tendinitis, in most cases this is just short lived. Furthermore, corticosteroid is contra-indicated for the treatment of loading tendons such as the patella tendon, Achilles tendon, and hamstring tendons because of the increased risk of rupture from tissue weakening. This is also the case with advanced cases of shoulder rotator cuff tendinitis and plantar fasciitis, as this has been associated with increased muscle tearing, and total ruptures in some cases. Both corticosteroids and anabolic steroids have been implicated in tendon ruptures. The injection of corticosteroids into the tendons has been shown to cause tendons cell death and inhibition of healing. In addition, corticosteroids can mask painful symptoms, causing the individual to overexert a weakened tendon. So this begs this question - should we be even using cortisone at all for the treatment of tendinopathy, or should we be concentrating on repair?! General advise is that it does have its place in acute cases of tendinitis with swelling, in non-weight bearing tendons like the shoulder or elbow, but a poor solution long term. A cortisone may be used to allow pain reduction to the degree where mild strengthening and rehabilitation treatment can occur. But, ultimately, an acute case of tendinitis often responds favourably to early intervention with conservative treatment.
Is the benefit of short-term pain relief worth causing more damage and risk long term? The issues relating to corticosteroid injections are therefore less that they do not work, but more that the benefits are generally short term, and that there is the potential for weakening the structural integrity of tendons in the long-term. The exact mechanism by which corticosteroids have an effect on tendon pain is unclear, in fact more data is indicating how repair is somewhat compromised. Corticosteroids are thought to reduce blood flow to the local area as well as exhibiting anti-inflammatory effects. They may also influence the perception of pain by altering local nociception (detection of pain). The challenge is to determine exactly how corticosteroids exert their beneficial effect on nociceptive and inflammatory pathways.
PRP and Tendon Repair
Treatment modalities such as non-steroidal anti-inflammatory drugs and corticosteroids can be used to treat tendinopathy but is not a long-term solution. Acute injury and chronic tears often require surgical intervention, but surgical outcomes can be unpredictable and associated with persistent pain, discomfort, and/or altered mobility or movement pathways. The poor self-repair capability of tendons and ligaments has led to an increased interest in platelet rich plasma (PRP). PRP is a mixture of highly concentrated platelets and associated growth factors. The growth factors released by PRP have been shown to promote cell recruitment, proliferation (laying) and angiogenesis (new blood vessels). It has also been examined that PRP induces a transient inflammatory event that triggers a regenerative response. Furthermore PRP is thought to have beneficial immuno-modulatory effects on tendon cells. Multiple meta-analyses have been published on PRP usage for tendon or ligament injuries.
A review of the literature by Chen and Vangsness (2018) on PRP treatment for tendon and ligament repair report that PRP for tendon and ligament damage is safe and effective. Of 1937 unique patients treated with PRP, no significant adverse events were reported. These results are in agreement with the existing literature, which concludes that PRP is a safe and effective treatment option for injured musculoskeletal tissues. The meta-analysis they conducted showed significant improvement in PRP-treated groups compared to control groups in patients with tendon and ligament injuries at both short-term and long-term follow-ups.
In addition to platelets, PRP contains varying levels of leukocytes (white blood cells WBCs) that may either positively or negatively affect the repair process. The decision to include or exclude WBCs in PRP application is a major point of controversy. Leukocytes have been associated with inflammatory cytokines which could have potentially effects on tissue regeneration. However, new research suggests this is not the case. For instance, a recent meta-analysis by Fitzpatrick et al., found that leukocyte-rich PRP, had a significantly greater positive effect on tendon healing than leukocyte-poor PRP. Furthermore, new research in going in the direction of using platelet rich fibrin (PRF) as opposed to PRP, which contains a much higher percentage of WBCs as the thought process is now that these are needed for greater tissue repair and regeneration.
Platelet activation is another subject of extensive research, as the addition or exclusion of activation agents is likely to impact the efficacy of PRP. Activation is suggested as a required process of PRP preparation for optimal release of growth factors. But many studies to date on the efficacy of PRP treatment in tendinopathy have not activated the PRP prior to use, thus de-valuing the PRP effect, and overall effecting the quality of the study. A recent study comparing PRP activated with calcium cloride (CaCl) had significantly higher growth factor release compared to non-activated PRP. This suggests that the underlying therapeutic efficacy of many current studies may be limited.
Tendon and ligament regeneration has proved a substantial goal for tissue engineering owing to the specialised nature of these tissues and the high mechanical demands placed on them. The mechanical environment impacts specialised cells that can alter tendon structure and cell viability. Future studies combining PRP and a biological scaffold have been proposed to help improve the structural performance of damaged and degenerated tissues. Studies have shown that, in tendon healing, biological scaffolds are used to stimulate healing and protect the healing area from detrimental forces. Platelet rich fibrin scaffold is an effective biological matrix that has huge potential. Interestingly, beside the enrichment in platelets and leukocytes, the entrapment of stem cells mediators with high regenerative potential within the fibrin network has recently been acknowledged providing an even more solid basis for the use in regenerative medicine. Platelet-derived growth factors (PD-GF)work as potent stimulators of tenogenesis (formation of new tendon cells) and chondrogenesis (formation of new cartilage cells) by regulating cell increases, inflammation, new blood cells and cell matrix deposition. The application of a single growth factor demonstrated a significant role in the enhancement of healing.
PD-GFs in Tendogenesis
Growth factors (GF) powerfully regulate cell biological responses, hence, their ability to stimulate tissue recovery and the differentiation of stem cells into new tissue. Administration of a single GF has been considered for tendon healing but administering a pool of bioactive GFs may boost regeneration. IGF-1 is one GF that has huge importance in stimulating new collagen and enhancing the metabolic response of new tendon cells. At the time of tendon injury, PD-GF peaks rapidly, being released from platelets, outlining the significant role in the early stages of healing. It has many functions, including new cell migration, the development of new blood vessels and activation of macrophages. Interestingly, it also promotes the production of other GFs including TGF-β1, IGF-1 and VEGF, confirming its leading role in healing processes.
The scientific rationale behind the use of platelet rich fibrin (PRF) is related to the ability to entrap platelets. This then acting as a reservoir of many GFs which can accelerate the healing process, controlling pain and inflammation. In addition, PRF is easy to obtain, and so are promptly available for clinical use.
Joint Conditions in Sport Injury Medicine
Biological treatments have been used for joint pain related conditions for quite some time now with the goal of not only to restore cartilage health but also to preserve cartilage by avoiding cartilage degradation and progression to osteoarthritis. A recent systematic review, including 844 interventions with a 21-month follow-up, showed joint stem cell treatments to be safe. Similarly, the safety of PRP injections was reported in with a follow up of 26 months.
When looking at the knee ligaments, the biological treatments mentioned above enhance tissue healing by stimulating the recovery processes for restoration of native or near-native tissue in addition to symptom management. The most popular biological modalities currently used in ortho-biologics include hyaluronic acid, platelet-rich plasma (PRP), and bone marrow aspirate concentrate. These treatments are used to facilitate bioactive factors to improve tissue healing. Various growth factors regulate and improve cellular activities and differentiation of mesenchymal stem cells into new tissues in the repair of joint ligaments. PRP application in ACL reconstruction surgery can also improve successful outcome; improving knee function and relieve pain after operation, at the same time is also accelerate graft remodeling.
Microfracture and autologous chondrocyte implantation appear to be the treatment reference for young patients with focal cartilage injuries, but the only disadvantage is that these treatments are invasive and very expensive. Furthermore, recent evidence has shown that outcomes after microfractures were better if patients received PRP treatment 6–24 h after the procedure.
Cartilage injuries, often with meniscal damage, will often lead to joint osteoarthritis. Advanced deterioration involves sclerotic bone, reduced joint space, subchondral bone marrow oedema, and synovitis, which are all often sources of pain. Likewise, anterior cruciate ligament (ACL) injuries, often lead to knee instability which can then lead to the cascade above. Joint injections of stem cells have been investigated in meniscal regeneration after meniscal surgery, with the combination of using hyaluronic acid injection treatment as control, with okay results. 2 recent meta-analyses have examined the efficacy of PRP injections. Shen et al., included 14 randomised control trials with a total of 1423 individuals and revealed that PRP was more effective than other treatments long term at 12 months in terms of pain reduction and functional improvement. Dai et al., included 10 randomised controlled trials with a total number of 1069 patients at 6 months and identified hyaluronic acid injection treatment and PRP shown similar good outcomes. Still, at long term 12 months, PRP was more effective. Furthermore, Guenoun et al., (2019) performed a study on the treatment of degenerative meniscal tear with intrameniscal injection of PRP treatment, which shown the treatment to be safe, reliable with good outcomes.
PD-GFs in Chondrogenesis
As mentioned above, platelet-derived growth factors work as potent stimulators of the formation of new cartilage cells, offering promising treatments for the enhanced regeneration of articular cartilage defects. The positive effects of PRP on articular cartilage regeneration have been seen out by several studies based on the of osteochondral defects, revealing an efficient capacity to promote cartilage healing. Like PRP, PRF also contains a wealth of GFs and cytokines released from the platelets. Thus, influencing the regenerative capabilities of articular cartilage, and ensuring superior mechanical performance which better meets the demands of the target tissue.
PDGF have been reported to stimulate new cartilage cells as well as inhibiting cell death. GFs have been shown to regulate articular cartilage metabolism in both healthy and disease conditions at the same time as decreasing catabolism (breakdown) and inducing the differentiation of new stem cells into cartilage. Gs demonstrate the potential to enhance cartilage repair and protect the synovial joint membranes from chronic inflammation.
Following PRF scaffold administration into the area of cartilage damage - macroscopic evaluations of repair tissue have been monitored and seen in new studies of cartilage healing. In particular, the International Cartilage Repair Society (ICRS) scoring system was the main reference for both macroscopic and microscopic assessment of the regenerated articular cartilage. Overall, clinical investigations revealed a significant improvement of cartilage regeneration after treatment, with some evidence of enhanced healing after combining with autologous cartilage stem cell administration.
PRF is considered as a second-generation platelet concentrate which is though to offer many advantages over first-generation PRP, by virtue of its 3-D fibrin matrix, ensuring favourable mechanical properties and the prolonged release of GFs, cytokines and regenerative cells. This defines PRF as a true biomaterial delivering the key players of the healing process, with improved potential for application in a wider range of clinical fields.
Hyaluronic Acid Injection Treatment
Hyaluronic acid (HA) is again a very common and successful treatment for mild to moderate cases of osteoarthritis. Hyaluronic acid is a joint lubricant and is used to nourish and protect cartilage. Moreover, it is used to slow the progression of degenerative changes. This form of treatment has demonstrated greater benefit of intra-articular hyaluronic acid within earlier stages of knee osteoarthritis (OA) rather than waiting for patients to have progressed to later stages of disease progression. HA is still a very safe and effective treatment option, and better still used in combination with PRP treatment.
The needs of conservative treatments within sports injury medicine has rapidly accelerated the clinical use of biological therapies, with ongoing success and clinical effectiveness. It is, however, essential that the correct protocols are adopted, along with the proper rehabilitation for optimal ongoing success, and the promotion of regenerative capacities.
Opinion - Mr Adam Whatley. Owner of Dynamic Regenerative Medicine
Biological regenerative treatments used within the high demand for sports injuries are processed with multiple aims. These include, mainly to facilitate and accelerate tissue healing, restore optional function and to establish tissue regenerative capacity. The field of regenerative medicine in tissue injury is based on sound scientific medical understanding, along with the physiological processes in molecular and cell biology in tissue damage and healing. Ultimately, we are looking at stimulating angiogenesis (production of new blood vessels) and promoting new cell migration to form new tissue in the optimal environment for repair mechanisms. Although, scepticism can exist among some, what we know is research takes time in an area of new development. However, this area is ever-evolving at a rapid rate with significant outcomes. Furthermore, the advantages of regenerative biological treatments are that these treatments are natural, safe and based on tissue recovery and regeneration as opposed to certain drug-related anti-inflammatory treatments like corticosteroid which have detrimental effects on tissue health with weakening and degradation. This is obviously a huge no-no with elite sports.
It is essential to note and understand that with urgent requirements to speed up recovery in elite athletes, and media coverage of anecdotic celebrity cases, have produced hype around certain regenerative forms of treatment. Direct internet marketing of stem cell treatments has also been a focus of criticism, due to ‘unsupporting’ claims of benefits.
Sports medicine and musculoskeletal doctors, along with and orthopaedic surgeons, have embraced PRP therapy due to expanding evidence-based clinical success and the fact that it is safe, time-efficient, affordable and delivers successful outcomes without the need for drug-based treatments. Although initially PRP was perceived as doping because, among the thousands of molecules it contains, a few were present in the World Anti-Doping Agency (WADA) list, the ban was lifted by 2010. In addition, PRP treatment is associated with fewer propaganda phrases like ‘cutting edge technology’ or ‘breakthrough stem cell treatment’. PRP therapies, when presented to the public are in the context of injury and pain, and are explained to have the treatment potential to a speedy recovery, facilitate healing and promote optimal function. During the last couple of decades, sports medicine has evolved toward an evidence-based practice along with clinical opinion and recommendation. The specific needs of each individual, along with the available and relevant clinical evidence for each independent musculoskeletal condition, should be considered in the decision-making process, thus, in addition to considering all predisposing factors. This should, in many cases, involve looking outside of the evidence-based box also; otherwise, this can form a ’robotic textbook clinician’ who lacks personal judgement. As the clinical and statistical evidence continues to build and develop in the exciting field of regenerative medicine, this will then begin to gain further understanding and drive medical decisions on the broader applications. Furthermore, an interdisciplinary collaboration between rehabilitation therapists, sports musculoskeletal clinicians, and orthopaedic surgeons will be necessary to explore the potential of biological therapies.
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