**6.1. Basic science**

Biologics are similar to the aforementioned injections, as they are injected into the RCT zone to assist in regeneration of the tendons. Biologics are specific proteins and cells that are obtained from the patient; therefore, they are personalised for the individual [64].

Biological injections can include platelet-rich plasma (PRP), which is prepared from a patient's blood by concentrating thrombocytes, usually a multiple of the normal circulating concentration. This injection is produced through standardised preparations: blood is drawn from the patient and spun in a centrifuge to separate the parts of the blood, and the highly concentrated plasma is re-administered to the patient in the affected area [65]. The idea of PRP follows simple scientific logic as the platelets are the body's primary way of reaching structural defects and injuries through proteins, cytokines, and growth factors that stimulate healing. Once platelets reach the specific site, they release different growth hormones that trigger natural and regenerative healing processes [66]. PRP has been known to stimulate both the response of mesenchymal stem cells (MSCs) to the local area through growth factors such as plateletderived growth factor (PDGF), fibroblast growth factor and vascular endothelial growth factor (VEGF) and stimulate tendon stem cells to differentiate into tenocytes when certain growth factors are released, which promotes healing of the rotator cuff [67, 68]. Furthermore, PRP can also assist in the proliferation of muscle cells [69], promoting inflammation [70], and the use of adhesion molecules to repair the torn tendon [71]. The proliferation of muscle cells allows for an increased number of fibroblasts and myotubes, thereby decreasing the overall time of recovery and increasing the strength of the rotator cuff [69]. Non-growth factors released from platelets such as serotonin, histamine, dopamine, calcium and adenosine aid in inflammation proliferation [70]. Finally, adhesion molecules such as fibronectin, fibrin and vitronectin can be delivered in a clot [71].

**7. Risks of conservative treatment in managing a rotator cuff tear**

symptoms.

the size of their tears.

Non-operative treatment has been recommended as an initial treatment for patients with rotator cuff pathology ranging from tendinopathy to partial and even complete RCTs [80]. Although several reviews and studies have demonstrated the effectiveness of non-operative treatment in RCTs, as previously described, there are concerns regarding the risks of conservative treatment as well. The overall goal of conservative management is to diminish pain, increase ROM and strength, and to ultimately decrease the functional limitations of the patient [81]. There appears to be some consensus that a conservative treatment program is a reasonable approach within the first 6–12 weeks in patients with non-traumatic tears under the age of 60 years. If the patient does not respond within the initial 4–6 weeks, then it can be an indicator for transition to surgical treatment. Edwards et al. [56] has demonstrated that if the patient does respond well, the conservative treatment will be effective for up to 2 years. Tanaka et al. [81] reviewed the literature and noted that conservative treatment is an effective method for the treatment of RCTs, with success rates ranging from 33 to 88%. The large variability appears to be dependent on the method of treatment chosen, as well as the observations and monitoring that occurs in between the pre-established patient follow-up dates. Although effective, the benefits of non-operative treatment have also been accompanied by progression of the tear, muscle atrophy, fatty infiltration, worse surgical outcomes and increased pain and

Complete Rotator Cuff Tear: An Evidence-Based Conservative Management Approach

http://dx.doi.org/10.5772/intechopen.70270

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Tempelhof et al. [15] studied asymptomatic RCTs longitudinally to improve the understanding of the risks of tear progression and pain development over time. The study followed patients for a median of 5.1 years, following the identification of the asymptomatic degenerative tear. They observed that tear enlargement occurred in a time-dependent manner with greater risks of enlargement relative to larger and more severe tears. This was observed in 110 of 224 patients (~49%) over an average span of 2.8 years. FTTs were 1.5–4 times more likely to enlarge than PTTs. In addition to the risk of tear progression, the transition from an asymptomatic tear to a symptomatic tear was observed due to the development of new pain, and the median time until pain developed was roughly 2.6 years. The development of new pain occurred in 46% of the patients, and the occurrence of symptoms correlated with an average enlargement rate of 63%, whereas those who remained asymptomatic had a 38% increase in

These results demonstrate the long-term potential for an FTT to increase in size over several years, which is in agreement with Hsu and Keener [82], who thought that the risks of tear progression and muscle atrophy are present early on, but the rate of progression is slow enough to allow adequate time to attempt conservative treatment [82]. They developed a stratification of the several treatment options in which the patients were categorised and recommended a treatment option based on their natural history and pathology. The system established by Hsu and Keener [82] contained three groups in which the risks of non-operative treatment varied and the potential benefits of surgery were optimised. The groups were assigned according to the symptoms presented at the time of the patient interview. In group I, early operative repair was recommended for acute tears, while those in group

MSCs can be found in a variety of locations throughout the human body, but are most commonly found around vascular tissue, bone marrow, and fat [72]. MSCs are derived from pericytes that detach from the blood vessels and become activated MSCs [72]. These stem cells, like many other stem cells, can proliferate and eventually differentiate into fully functional osteocytes, adipocytes, and fibroblasts or remain as activated MSCs [73]. MSCs can be both immunomodulatory and trophic, which aid in regeneration. The cells can act as an autoimmune response to combat pathogens that infect the ruptured tissue [74]. Further, MSCs inhibit both apoptosis (cell death) and scar formation while stimulating angiogenesis and mitosis (through the secretion of mitogens) [64]. Because of the many functions of MSCs, the activation of MSCs is critical in the healing process. These activated MSC cells provide the damaged part with necessary chemicals to heal itself more quickly.

#### **6.2. Laboratory investigation**

An in vitro study found that PRP stimulated cell proliferation and the synthesis of tenocytes in RCTs [75]. In an experiment in which rats were treated for RCT, the group given the PRP treatment demonstrated better collagen linear alignment. Furthermore, the research team found positive effects when administering the PRP injections 3 weeks after the initial surgery [76].

#### **6.3. Clinical investigation**

A clinical trial in 2012 found reduced pain and positive effects in the healing process of RCTs [77]. These clinical trials demonstrate the effect PRP has in stimulating the already present natural healing process.

A commonly used source for regenerative injection therapy (RIT) is bone marrow aspirate that is centrifuged to form a concentrate. Bone marrow aspirate concentrate (BMAC) can possess a number of different stem or progenitor cells that can aid in the body's natural selfregenerative processes [78]. BMAC can be used as a regenerative injection therapy for various injuries and primary conditions, as well as be used during surgery. One study compared BMAC augmented surgery vs. arthroscopic repair alone. Of the 45 patients augmented with BMAC, 100% of patients were healed 6 months after surgery compared to 67% of the 45 control patients. At 10-year follow-up found that 87% of patients in the BMAC group compared with 44% of control patients were healed [79].
