Review
Copyright ©The Author(s) 2015. Published by Baishideng Publishing Group Inc. All rights reserved.
World J Orthop. Mar 18, 2015; 6(2): 211-220
Published online Mar 18, 2015. doi: 10.5312/wjo.v6.i2.211
Factors affecting healing after arthroscopic rotator cuff repair
Amir M Abtahi, Erin K Granger, Robert Z Tashjian
Amir M Abtahi, Erin K Granger, Robert Z Tashjian, Department of Orthopaedic Surgery, University of Utah, Salt Lake City, UT 84108, United States
Author contributions: Abtahi AM, Granger EK and Tashjian RZ solely contributed to the concept, writing and editing of this paper.
Open-Access: This article is an open-access article which was selected by an in-house editor and fully peer-reviewed by external reviewers. It is distributed in accordance with the Creative Commons Attribution Non Commercial (CC BY-NC 4.0) license, which permits others to distribute, remix, adapt, build upon this work non-commercially, and license their derivative works on different terms, provided the original work is properly cited and the use is non-commercial. See: http://creativecommons.org/licenses/by-nc/4.0/
Correspondence to: Robert Z Tashjian, MD, Department of Orthopaedic Surgery, University of Utah, 590 Wakara Way, Salt Lake City, UT 84108, United States. robert.tashijan@hsc.utah.edu
Telephone: +1-801-5875457 Fax: +1-801-5875411
Received: July 4, 2014
Peer-review started: July 4, 2014
First decision: July 18, 2014
Revised: September 29, 2014
Accepted: October 1, 2014
Article in press: October 10, 2014
Published online: March 18, 2015

Abstract

Rotator cuff repair has been shown to have good long-term results. Unfortunately, a significant proportion of repairs still fail to heal. Many factors, both patient and surgeon related, can influence healing after repair. Older age, larger tear size, worse muscle quality, greater muscle-tendon unit retraction, smoking, osteoporosis, diabetes and hypercholesterolemia have all shown to negatively influence tendon healing. Surgeon related factors that can influence healing include repair construct-single vs double row, rehabilitation, and biologics including platelet rich plasma and mesenchymal stem cells. Double-row repairs are biomechanically stronger and have better healing rates compared with single-row repairs although clinical outcomes are equivalent between both constructs. Slower, less aggressive rehabilitation programs have demonstrated improved healing with no negative effect on final range of motion and are therefore recommended after repair of most full thickness tears. Additionally no definitive evidence supports the use of platelet rich plasma or mesenchymal stem cells regarding improvement of healing rates and clinical outcomes. Further research is needed to identify effective biologically directed augmentations that will improve healing rates and clinical outcomes after rotator cuff repair.

Key Words: Shoulder, Repair, Healing, Tendon, Rotator cuff tear

Core tip: Many factors, both patient and surgeon related, can influence healing after repair. Older age, larger tear size, worse muscle quality, greater muscle-tendon unit retraction, smoking, osteoporosis, diabetes and hypercholesterolemia have all shown to negatively influence tendon healing after rotator cuff repair. Smoking cessation and blood glucose and cholesterol control are methods to potentially improve healing rates. Slower, less aggressive rehabilitation programs may improve healing rates with no negative effect on final range of motion and are therefore recommended after arthroscopic repair of most full thickness tears. Finally, no definitive evidence supports the use of platelet rich plasma or mesenchymal stem cells regarding improvement of healing rates after rotator cuff repair. Routine use of these adjuvants is therefore not currently recommended.



INTRODUCTION

Rotator cuff tears are a common cause of pain and disability[1,2]. In patients meeting indications for surgery, rotator cuff repair has been shown to have good long-term clinical results[3,4]. Despite this, the literature suggests that a significant proportion of repairs fail to heal following rotator cuff repair. Reported healing rates vary from 91% for small tears to 6% for large and/or massive tears in some series[5-8]. Failure of tendon healing does not necessarily preclude satisfactory results, although improved results have been associated with intact repairs[9,10]. There is a large body of literature demonstrating that a number of different factors may influence the results following rotator cuff repair. In general, factors can be separated into patient-related (non-modifiable) and surgeon-related (modifiable). The purpose of this review is intended to provide a summary of the literature related to the major factors, both patient- and surgeon-related, influencing healing after rotator cuff repair.

PATIENT-RELATED FACTORS
Age

Increasing patient age has been associated with lower rates of tendon healing after rotator cuff repair in multiple studies[5,11-13]. The detrimental effect of age on rotator cuff tendon healing appears to be independent of the surgical technique utilized for repair. Boileau et al[5], in a series of 65 chronic full-thickness supraspinatus tears repaired via an arthroscopic single row technique, reported 43% healing in patients over 65% vs 86% healing in patients under age 65. Tashjian et al[11], in a series of 49 arthroscopic double-row rotator cuff repairs, reported that increased age was associated with lower rates of tendon healing. The average age of patients with unhealed repairs was 63.3 vs 55.1 for those with healed repairs[11]. Similarly, Cho et al[12], in a study of 123 arthroscopic double-row suture bridge repairs, demonstrated that increasing age was associated with lower rates of tendon healing. The average age of patients with unhealed repairs in their series was 60.1 compared to 53.8 in the healed group. Finally, Oh et al[13], in a study of 177 patients after arthroscopic and mini-open rotator cuff repairs of various techniques, also noted that increasing age was associated with lower rates of tendon healing. The average age of patients with unhealed repairs in their series was 63.7 compared to 58.4 in the healed group[13].

The detrimental effect of increasing age on tendon healing after rotator cuff repair may be due to other factors affecting tendon healing rather than to age itself. Chung et al[14], in a study of 272 patients after arthroscopic rotator cuff repair, found that bone mineral density, fatty infiltration, and retraction of the rotator cuff tendon were the only independent predictors of rotator cuff healing. Chung et al[15], in another study of 108 patients who underwent arthroscopic repair of massive rotator cuff tears, found that while several factors were associated with failure of cuff healing in the univariate analysis including age, only fatty infiltration was significantly related to healing failure in the multivariate analysis. Similarly, Oh et al[13] noted that age was not an independent predictor of tendon healing or functional outcome. Tear retraction and fatty atrophy were found to be the only independent predictors of tendon healing in their study[13]. Therefore, age may be a surrogate for other anatomical factors correlated with impaired healing after rotator cuff repair.

Tear size

Several studies have shown that tear size affects rotator cuff tendon healing. Larger tears have lower healing rates after rotator cuff repair compared to smaller tears. Failure rates after arthroscopic repair of large and/or massive rotator cuff repairs have been reported to range from 34%-94% in various series[6,16-19]. Despite poor healing rates in patients with large and/or massive rotator cuff tears, functional outcomes have generally been reported to be good following repair. Galatz et al[6] reported that despite failure of healing in 94% of patients at 1 year follow-up, excellent pain relief and improvement in the ability to perform activities of daily living was noted although these results did deteriorate somewhat at 24 mo follow-up. Chung et al[15] reported significantly improved functional improvement in a series of arthroscopically repaired massive cuff tears despite an anatomic failure rate of 39.8%. Despite this, not all patients with an unhealed repair do well clinically[18-21]. Namdari et al[21] reviewed a series of patients with structural failure after rotator cuff repair and reported a successful outcome in only 54% of patients. Those individuals with labor-intensive jobs were also found to be at high risk for poor outcome after a failed rotator cuff repair[21]. Kim et al[20] reviewed a similar group and determined younger age, lower education level and a workers’ compensation claim were all risk factors for poorer outcomes after a failed repair.

Fatty infiltration and rotator cuff atrophy

Fatty infiltration and rotator cuff atrophy have been shown to affect healing and functional outcomes following rotator cuff repair[10,22,23]. Thomazeau et al[22] demonstrated that more severe preoperative atrophy was associated with worse postoperative repair integrity in 30 open repairs of chronic supraspinatus tears. Liem et al[10], in a series of 53 arthroscopic repairs of isolated supraspinatus tears, reported that both supraspinatus atrophy and fatty infiltration were predictive of healing. Goutallier et al[23], in a series of 220 shoulders, demonstrated that the likelihood of recurrent tear was greater in patients whose muscle demonstrated more advanced degrees of fatty atrophy. Despite lower rates of cuff healing, patients with fatty infiltration and rotator cuff atrophy may still benefit from rotator cuff repair. Burkhart et al[24] reported on 22 patients with massive rotator cuff tears and Goutallier stage 3 or 4 fatty degeneration undergoing arthroscopic rotator cuff repair and demonstrated significant overall functional improvement. Patients with a greater degree of fatty degeneration, however, were less likely to benefit from surgical intervention than those with less fatty degeneration[24]. Other studies have also shown that patients with fatty infiltration and rotator cuff atrophy have lower rates of tendon healing associated with inferior clinical outcomes[10,25]. Goutallier grade 2 or higher degrees of fatty infiltration are significantly associated with poorer healing after repair[10].

Although rotator cuff atrophy and fatty infiltration are both considered part of the same process, they have been found to independently predict outcome following rotator cuff repair[25]. Most studies indicate that fatty infiltration is irreversible, even in the presence of a successful repair. In the presence of an untreated or failed repair, fatty infiltration continues to progress. In some studies, atrophy has been shown to improve to a small degree after successful repair. Fuchs et al[26] in a series of single tendon rotator cuff repairs reported that muscular atrophy did not decrease significantly after repair. However, fatty infiltration of the supraspinatus and infraspinatus, increased significantly despite repair. Rotator cuff atrophy was significantly worse in patients with re-tears than in those with intact repairs. Gerber et al[27], in a study of 12 patients, noted that within one year after successful tendon repair, fatty infiltration did not improve but rotator cuff atrophy improved partially. In the presence of a failed repair, atrophy and infiltration progressed significantly. In a separate study, Gerber et al[19] studied 29 patients who underwent arthroscopic repair of massive rotator cuff tears and noted a 34% retear rate. Supraspinatus atrophy was mildly reversed after repair. Infraspinatus atrophy, however, worsened even after successful repair. Fatty infiltration was not reversible but progressed less in patients with intact repairs. Chung et al[28] reported, in a series of 191 patients who underwent arthroscopic rotator cuff repair, that 42.4% of patients showed improvement of atrophy and 17.3% of patients showed worsening. The change in atrophy was related to repair integrity. For patients with worsened atrophy, the cuff healing rate was 48.5% compared with 22.2% in patients with improved atrophy. Gladstone et al[25], in a study of 38 patients after arthroscopic rotator cuff repair found that both atrophy and infiltration progressed regardless of rotator cuff healing. In cases in which the tendon had re-torn however, the progression was noted to be more significant compared to those patients that had healed. Liem et al[10] in a series of 53 consecutive patients who underwent arthroscopic repair of an isolated supraspinatus tear, reported that in patients with intact repairs fatty infiltration and atrophy did not progress whereas in those with recurrent tears fatty infiltration and atrophy worsened significantly. So overall, fatty infiltration may halt after a repair if it remains intact but will progress with re-tears. Atrophy has the potential to reverse after repair if the repair remains intact but will likely progress if it fails.

Muscle-tendon unit retraction

Tendon retraction, or the gap between the greater tuberosity and the tendon edge, is either due to tendon shortening or muscle retraction. Muscle retraction can be defined by utilizing the position of the muscle-tendon junction (MTJ) in relation to landmarks on the scapula. Meyer et al[29] evaluated 118 shoulder MRIs for the MTJ position in the setting of a rotator cuff tear. They concluded that increasing stages of fatty infiltration correlate with increasing tear size, tendon shortening and MTJ retraction. Initial stages of muscle-tendon unit retraction in the setting of rotator cuff tears with minimal fatty infiltration occurs through muscle shortening whereas tears with later stages of fatty infiltration shorten through tendon shortening[29]. Kim et al[30] reported similar results that showed with increasing tear size and tendon reaction, the tendon length shortens. These results support that initial retraction in smaller tears occur with muscle shortening but as tears enlarge and become more chronic the tendon shortens as well.

Meyer et al[31] also looked at the effect of MTJ shortening on rotator cuff repair healing. They determined that the muscle and tendon lengthened an average of 14 mm and 8 mm, respectively, after a successful rotator cuff repair. They also determined that a shorter preoperative tendon length correlated with worse overall healing rates although preoperative MTJ position had no effect[31]. Tashjian et al[32] evaluated MRIs of 51 patients after arthroscopic rotator cuff repair and did find a significant associate with preoperative MTJ position and postoperative tendon healing. If the preoperative MTJ was at the level of the glenoid or medial then 55% of tears healed whereas if the MTJ was lateral to the glenoid face then 93% of tears healed. Consequently, both greater preoperative MTJ retraction and greater preoperative tendon shortening negatively affect healing after rotator cuff repair.

Other patient-related factors (smoking, osteoporosis, hypercholesterolemia, diabetes)

Several other patient-related factors have been reported to affect rotator cuff tendon healing. Smoking not only increases the risk for rotator cuff tears, but has been reported to influence rotator cuff tear size as well[33]. Smoking has been shown to delay tendon-to-bone healing in a rat model and clinical studies have demonstrated inferior clinical outcomes after repair in smokers[34,35]. Finally, Neyton et al[36] evaluated healing after arthroscopic double-row suture bridge repair for the impact of smoking. The authors determined healing rates were significantly worse in smokers (78%) compared to non-smokers (93%) after single tendon repair.

Both bone mineral density and vitamin D deficiency have been shown to affect rotator cuff tendon healing following surgical repair. Chung et al[14], in a study of 272 patients after arthroscopic rotator cuff repair, found that bone mineral density was an independent predictors of rotator cuff healing. In a rat rotator cuff repair model, Angeline et al[37] demonstrated that vitamin D deficiency negatively affects the biomechanical and histological properties of rotator cuff repairs during the early phase of healing. This effect was found to be independent of bone mineral density[37].

Other system diseases have been associated with rotator cuff tearing as well as rotator cuff healing. Abboud et al[38] collected serum cholesterol and lipid profiles on patients with full-thickness rotator cuff tears and compared them to a control population. They determined that total cholesterol, triglycerides and low-density lipoprotein cholesterol concentrations were higher in patients with rotator cuff tears. Consequently, patients with cuff tears are more likely to have hypercholesterolemia compared to controls. Beason et al[39] evaluated the effects of hypercholesterolemia on tendon healing in a rat rotator cuff tear model. These authors determined that there was a significant reduction in rotator cuff repair stiffness in hypercholesterolemic rats compared with controls[40]. This data would support hypercholesterolemia likely plays a role not only in the development of rotator cuff tearing but also on the ability for a tendon to heal after repair. Similarly, diabetes has been found to have a detrimental effect on tendon healing using a rat rotator cuff tear model[39]. Modification of serum cholesterol levels and blood glucose levels may play a role in improving healing after repairs.

SURGEON-RELATED FACTORS
Repair construct-single-row vs double-row

A number of surgical techniques are available to the surgeon treating tears of the rotator cuff. An ideal rotator cuff repair construct would provide high initial fixation strength and minimize gap formation during healing[41]. Biomechanical studies of double-row repairs have shown increased load to failure, improved contact areas and pressures, and decreased gap formation when compared to single row repairs[42-46]. These biomechanical studies have led to a number of clinical studies comparing single-row with double-row repair techniques. These studies have, in general, failed to demonstrate significant differences in functional outcomes with single vs double-row techniques. Grasso et al[47] in a prospective randomized study of single-row vs double-row arthroscopic rotator cuff repairs reported that arthroscopic rotator cuff repair with the double-row technique showed no significant difference in clinical outcome compared with single-row repair. In contrast, Park et al[48] reported that in patients with large to massive tears (> 3 cm), the American Shoulder and Elbow Surgeons Score, Constant scores and Shoulder Strength Index were all significantly better in the group that had double-row repair.

Despite the fact that most studies have failed to demonstrate clinical differences with singe vs double row repairs at short term follow-up, there appears to be a lower re-tear rate for the double-row compared with the single-row repairs[49-51]. Lapner et al[49], in a multicenter randomized controlled trial comparing single-row with double-row fixation in arthroscopic rotator cuff repairs reported that although double-row fixation was associated with higher healing rates, no significant differences in functional or quality-of-life outcomes were identified between single-row and double-row fixation techniques. In contrast, Burks et al[52], in a prospective randomized clinical trial comparing arthroscopic single- and double-row rotator cuff repair reported no clinical or MRI differences between single-row or double-row techniques.

A modification of the double-row technique is the double-row suture bridge technique[36,53-56]. Gartsman et al[54], evaluated the repair integrity of single-row vs double-row suture bridge arthroscopic rotator cuff repairs in a prospective, randomized study. They demonstrated that double-row suture bridge repair resulted in a significantly higher tendon healing rate compared to arthroscopic single-row repair. Mihata et al[53] demonstrated that in the subcategory of large and massive rotator cuff tears, the re-tear rate in the double-row suture bridge group was significantly less than those in the single-row group and the non-suture bridge double-row group. Several techniques have been described for double row suture bridge repair. Kim et al[55] compared three different methods including knotted and knotless techniques and demonstrated equivalence between techniques with regards to functional outcomes and repair integrity.

An alternative to double row repairs for improving fixation and healing is to increase the number of sutures per anchor. Jost et al[57] evaluated the effects of increasing suture number on rotator cuff healing strength in a sheep model and determined that increasing the number of sutures decreased cyclic gap formation and increased load to failure. Barber et al[58] determined that single row repairs utilizing triple-loaded anchors were more resistant to cyclic displacement than double-row suture bridge repairs. Other authors have evaluated various suture configurations for rotator cuff repair. White et al[59], in a biomechanical study, reported no difference in biomechanical strength with 4 simple sutures, 2 mattress sutures, or 1 grasping suture. They concluded that this provides justification for the use of the simplest configuration with which the surgeon is comfortable.

Overall, the biomechanical data would support that double-row fixation is stronger than single row fixation using double-loaded suture anchors although increasing suture numbers per anchor (triple-loaded anchors) may offset any biomechanical advantage of double row repairs. Clinically, double-row repairs have improved healing rates compared to single row repairs using double-loaded suture anchors. Nevertheless, functional outcomes between double-row and single-row repairs are equivalent except in large and massive tears where double-row fixation may provide a functional advantage over single-row repairs.

Rehabilitation

A number of rehabilitation protocols have been described for use following rotator cuff repair. While some surgeons recommend early, aggressive rehabilitation programs, others recommend a more conservative rehabilitation program. Data are conflicting on which, if any, of these programs provides superior results. Early aggressive rehabilitation programs have been shown to result in better early outcomes, pain relief, and range of motion however most studies show no difference with regard to these parameters with longer-term follow-up[60-66]. One concern with early aggressive rehabilitation programs is that they may be associated with a higher incidence of tendon re-tear.

Immobilization has been shown to affect tendon healing although the data is conflicted. Galatz et al[67] and Hettrich et al[68] have shown that complete removal of load is detrimental to rotator cuff healing. In contrast, Gimbel et al[69] demonstrated that long durations of immobilization in rats result in enhanced mechanical properties of the healing supraspinatus tendon insertion site.

Like the basic science literature, the clinical literature is also conflicting as to whether the rehabilitation program utilized affects clinical healing rates after rotator cuff repair. While some studies show higher re-tear rates with early, aggressive therapy protocols, others show a trend or no difference in re-tear rates[62,63]. In a prospective randomized study of early aggressive vs delayed rehabilitation protocols, Cuff et al[63] demonstrated a slightly higher but non statistically significant re-tear rate at 1 year in the early group (15%) compared to the delayed group (9%). Lee et al[62] evaluated re-tear rates at 6 mo comparing aggressive with conservative rehabilitation protocols. They found that the re-tear rate was significantly higher in the more aggressive group (23.3%) compared with the conservative group (8.8%). They found no difference, however, in long-term functional outcomes between the two groups[62]. In contrast, Kim et al[61] evaluated early and delayed range of motion protocols after rotator cuff repair and found no statistically significant difference in healing rates between the two groups with a trend toward lower re-tear rates in the early range of motion group (12% vs 18%).

In summary, the literature shows that early aggressive rehabilitation protocols may result in a slightly higher incidence of re-tear compared with more conservative protocols. The benefits of early aggressive therapy protocols seen in the early postoperative period on pain relief and range of motion, however, are not observed with longer term follow up. The risk, therefore, may outweigh the benefits of such protocols in the majority of cases supporting the use of a slower rehabilitation protocol.

BIOLOGICS
Platelet rich plasma

Biologic augmentation of rotator cuff repairs has gained significant interest over the past several years as biomechanically improvements in repair constructs have maximized. Numerous growth factors have been shown to improve proliferation and collagen secretion of tenocytes in vitro including basic fibroblast growth factor, vascular endothelial growth factor, and transforming growth factor-β[70-74]. Platelet-rich plasma (PRP) is a fraction of whole blood containing high platelet counts that release these various growth factors when activated. Because these growth factors have shown a positive effect on healing in vitro, a large interest exits in the application of PRP to augment rotator cuff repair healing.

Several studies have been performed evaluating the effect of PRP on rotator cuff healing. There is currently no consensus on PRP application during rotator cuff repair as several studies have shown a positive effect on healing while others have shown no effect or a negative effect. Weber et al[75] performed a prospective randomized study evaluating the effects of platelet rich fibrin matrix (PRFM) on tendon healing and found no differences in healing rates in PRFM treated repairs compared to controls. Rodeo et al[76] reported similar results for PRFM in a randomized control trial where healing rates in the PRFM group were 67% compared to 81% in the non-augmented repairs (P = 0.2). Bergeson et al[77] actually reported significantly worse healing rates with PRFM application vs non-augmented repairs (38% vs 56%, P = 0.024).

Contrary to the findings reporting no effect of PRP on tendon healing, several authors have found beneficial effect of PRP on rotator cuff healing[78,79]. Barber et al[78] reported on a matched group of rotator cuff repairs treated with PRFM and non-augmented repairs and reported healing rates of 70% with PRFM augmentation and 40% without augmentation. Jo et al[79] performed a randomized control trial comparing PRP repair augmentation of large and massive rotator cuff tears and reported re-tear rates in the PRP augmentation group (20%) significantly lower than in the non-augmented group (56%) (P = 0.023).

At this point in time, it is unclear why certain studies have performed well with augmentation and others have found no improvement. Potential factors may be preparation mechanisms, timing of application and technique of repair to name only a few. Until further research is performed to elucidate which patients and through which technique PRP application may be beneficial, the use of PRP as an augmentation to rotator cuff repair to improve healing is experimental and of questionable utility.

Mesenchymal stem cells

Mesenchymal stem cells (MSCs) have been explored as an option for biologic augmentation of rotator cuff repairs. Mazzocca et al[80] have demonstrated that MSCs can be isolated from the proximal humerus through the anchor tunnels created during arthroscopic rotator cuff repair. Utsunomiya et al[81] investigated multiple potential sources of MSCs that can be harvested during arthroscopic rotator cuff repair. They demonstrated that synovial cells harvested from the subacromial bursa are a good potential source of MSCs[81]. Gulotta et al[82] evaluated MSCs in an animal rotator cuff repair model and found that the addition of MSCs to the healing rotator cuff insertion site did not improve the structure, composition, or strength of the healing tendon attachment site despite evidence that they are present and metabolically active[82]. In a subsequent publication, however, the authors reported that bone marrow-derived MSCs transduced with scleraxis (a transcription factor that is thought to direct tendon development during the embryonic period) improved rotator cuff healing in a rat model[83]. Similarly, Mazzocca et al[84] have demonstrated that bone marrow-derived MSCs treated with insulin differentiated into tendon-like cells. Kim et al[85], in an animal model, demonstrated that MSCs increase type I collagen production at the site of rotator cuff repair. Finally, Hernigou et al[86] evaluated forty-five patients that received concentrated bone marrow derived MSCs as an adjunct to single row rotator cuff repair compared to a matched control group and found that the healing rate at 6 mo was significantly higher in the MSC group. Furthermore, the authors found that at a mean follow-up of ten years there was a significantly higher re-tear rate in the control group compared to the MSC group[86]. Although use of MSCs demonstrates promise for biologic augmentation of rotator cuff repair, further clinical studies are necessary before their use can be recommended in clinical practice.

CONCLUSION

In summary, multiple factors have been shown to influence rotator cuff healing. Table 1 provides a summary of these factors and the relevant studies. Older age, larger tear size, worse muscle quality, greater muscle-tendon unit retraction, smoking, osteoporosis, diabetes and hypercholesterolemia have all shown to negatively influence tendon healing. Smoking cessation and blood glucose and cholesterol control are methods to potentially improve healing rates. Double-row rotator cuff repairs are biomechanically stronger and have better overall healing rates when compared to single-row repairs although clinical outcomes are equivalent between both repair constructs. Delayed rehabilitation after arthroscopic repair of most full thickness tears may improve healing rates with no negative effect on final range of motion therefore slower early rehabilitation can be recommended. Finally, no definitive evidence supports the use of platelet rich plasma regarding improvement of healing rates after rotator cuff repair therefore routine use is not currently recommended. Further research is required to identify effective biologically directed augments that will improve healing rates and clinical outcomes after rotator cuff repair.

Table 1 Studies evaluating factors affecting healing after rotator cuff repair.
StudyStudy typeNumber of patients/duration of follow upPrimary outcomeConclusionLevel of evidence
Age
Boileau et al[5]Case series65 pts/29 moCT arthrogram, MRIHealing rate significantly lower in patients > age 65IV
Tashjian et al[11]Case series48 pts/16 moUSOlder age associated with lower tendon healing rateIV
Cho et al[12]Case series120 pts/25.2 moMRIOlder age associated with lower tendon healing rateIV
Oh et al[13]Case series177 pts/29 moCT arthrogramOlder age was related to poor postoperative repair integrityIV
Tear size
Galatz et al[6]Case series18 pts/36 moUSHigh rate of tendon healing failureIV
Chung et al[15]Case series108 pts/31.7 moCT arthrogram, USHigh rate of tendon healing failureIV
Fatty infiltration/atrophy
Thomazeau et al[22]Case series30 pts/21.1 moMRISupraspinatus atrophy was a strong risk factor for retearIV
Liem et al[10]Case series53 pts/26.4 moMRIHigher degrees of muscular atrophy and fatty infiltration preoperatively are associated with tear recurrenceIV
Goutallier et al[23]Case series220 shoulders/37 moCT arthrogram, MRIThe likelihood of a recurrent tear was greater for tendons whose muscle showed fatty degeneration greater than grade 1IV
Chung et al[15]Case series108 pts/31.7 moCT arthrogram, USHigher FI of the infraspinatus was the single most important factor negatively affecting cuff healingIV
Tendon retraction
Meyer et al[31]Retrospective cohort33 shoulder/24 moMRIThe combination of Goutallier grading and preoperative tendon length appears to be a more powerful predictor for the reparability of a tendon tear than Goutallier grading aloneIII
Tashjian et al[32]Case series51 pts/25 moMRIThe position of the MTJ with respect to the glenoid face can be predictive of healing, with over 90% healing if lateral and 50% if medial to the faceIV
Other patient factors
Neyton et al[36]Case series105 pts/16.1 moMRISmoking was detrimental to healingIV
Chung et al[14]Retrospective cohort408 pts/37.2 moCT arthrogram, USBone mineral density, as well as FI of the infraspinatus and amount of retraction, was an independent determining factor affecting postoperative rotator cuff healingIII
Abboud et al[38]Case-control147 pts/NANAPatients with rotator cuff tears were more likely to have hypercholesterolemia when compared with the control groupII
Repair construct
Lapner et al[49]RCT90 pts/24 moMRI, USSmaller initial tear size and a double-row fixation technique were associated with higher healing ratesI
Burks et al[52]RCT40 pts/12 moMRINo clinical or MRI differences found between patients repaired with a SR or DR techniqueI
Mihata et al[53]RCT201 pts/38.5 moMRI, USRetear rate in the compression double-row group was significantly less than in the single-row group and the double-row groupI
Gartsman et al[54]RCT90 pts/10 moUSArthroscopic double-row suture bridge repair resulted in a significantly higher tendon healing rate compared to single-row repairI
Kim et al[55]Case series79 pts/30.6 moMRI, USThe re-tear rate after suture-bridge repair was 15%IV
Rehabilitation
Lee et al[62]RCT64 shoulders/7.6 moMRIMore patients in the aggressive early passive rehabilitation group (23.3%) had retears compared to the limited early passive group (8.8%) although not statistically significantII
Kim et al[61]RCT105 pts/12 moMRI, CT arthrographyEarly passive motion did not negatively affect cuff healingI
Biologics (PRP/MSCs)
Weber et al[75]RCT60 pts/12 moMRIHealing rates did not differ between groupsI
Rodeo et al[76]RCT79 pts/12 wkUSNo differences in tendon-to-bone healing between the PRFM and control groupsII
Bergeson et al[77]Prospective cohort37 pts/27 mo in control group and 13 mo in PRFM groupMRINo differences in retear rates between the PRFM and control groupsIII
Barber et al[78]Case-control40 pts/31 moMRIPRFM group had lower retear rates than control groupIII
Jo et al[79]RCT48 pts/15.9 in PRP group and 17.3 in control groupMRIRetear rate in the PRP group was significantly lower than in the control groupI
Hernigou et al[86]Case-control90 pts/10 yrMRIHigher rate of healing and reduced number of re-tears over time in the MSC groups compared to the control groupIII
Footnotes

P- Reviewer: Drosos GI, Teresa Valenti M S- Editor: Song XX L- Editor: A E- Editor: Liu SQ

References
1.  Chakravarty K, Webley M. Shoulder joint movement and its relationship to disability in the elderly. J Rheumatol. 1993;20:1359-1361.  [PubMed]  [DOI]
2.  Mather RC, Koenig L, Acevedo D, Dall TM, Gallo P, Romeo A, Tongue J, Williams G. The societal and economic value of rotator cuff repair. J Bone Joint Surg Am. 2013;95:1993-2000.  [PubMed]  [DOI]
3.  Galatz LM, Griggs S, Cameron BD, Iannotti JP. Prospective longitudinal analysis of postoperative shoulder function : a ten-year follow-up study of full-thickness rotator cuff tears. J Bone Joint Surg Am. 2001;83-A:1052-1056.  [PubMed]  [DOI]
4.  Zandi H, Coghlan JA, Bell SN. Mini-incision rotator cuff repair: a longitudinal assessment with no deterioration of result up to nine years. J Shoulder Elbow Surg. 2006;15:135-139.  [PubMed]  [DOI]
5.  Boileau P, Brassart N, Watkinson DJ, Carles M, Hatzidakis AM, Krishnan SG. Arthroscopic repair of full-thickness tears of the supraspinatus: does the tendon really heal? J Bone Joint Surg Am. 2005;87:1229-1240.  [PubMed]  [DOI]
6.  Galatz LM, Ball CM, Teefey SA, Middleton WD, Yamaguchi K. The outcome and repair integrity of completely arthroscopically repaired large and massive rotator cuff tears. J Bone Joint Surg Am. 2004;86-A:219-224.  [PubMed]  [DOI]
7.  Lafosse L, Brozska R, Toussaint B, Gobezie R. The outcome and structural integrity of arthroscopic rotator cuff repair with use of the double-row suture anchor technique. J Bone Joint Surg Am. 2007;89:1533-1541.  [PubMed]  [DOI]
8.  Frank JB, ElAttrache NS, Dines JS, Blackburn A, Crues J, Tibone JE. Repair site integrity after arthroscopic transosseous-equivalent suture-bridge rotator cuff repair. Am J Sports Med. 2008;36:1496-1503.  [PubMed]  [DOI]
9.  Harryman DT, Mack LA, Wang KY, Jackins SE, Richardson ML, Matsen FA. Repairs of the rotator cuff. Correlation of functional results with integrity of the cuff. J Bone Joint Surg Am. 1991;73:982-989.  [PubMed]  [DOI]
10.  Liem D, Lichtenberg S, Magosch P, Habermeyer P. Magnetic resonance imaging of arthroscopic supraspinatus tendon repair. J Bone Joint Surg Am. 2007;89:1770-1776.  [PubMed]  [DOI]
11.  Tashjian RZ, Hollins AM, Kim HM, Teefey SA, Middleton WD, Steger-May K, Galatz LM, Yamaguchi K. Factors affecting healing rates after arthroscopic double-row rotator cuff repair. Am J Sports Med. 2010;38:2435-2442.  [PubMed]  [DOI]
12.  Cho NS, Lee BG, Rhee YG. Arthroscopic rotator cuff repair using a suture bridge technique: is the repair integrity actually maintained? Am J Sports Med. 2011;39:2108-2116.  [PubMed]  [DOI]
13.  Oh JH, Kim SH, Kang JY, Oh CH, Gong HS. Effect of age on functional and structural outcome after rotator cuff repair. Am J Sports Med. 2010;38:672-678.  [PubMed]  [DOI]
14.  Chung SW, Oh JH, Gong HS, Kim JY, Kim SH. Factors affecting rotator cuff healing after arthroscopic repair: osteoporosis as one of the independent risk factors. Am J Sports Med. 2011;39:2099-2107.  [PubMed]  [DOI]
15.  Chung SW, Kim JY, Kim MH, Kim SH, Oh JH. Arthroscopic repair of massive rotator cuff tears: outcome and analysis of factors associated with healing failure or poor postoperative function. Am J Sports Med. 2013;41:1674-1683.  [PubMed]  [DOI]
16.  Gulotta LV, Nho SJ, Dodson CC, Adler RS, Altchek DW, MacGillivray JD. Prospective evaluation of arthroscopic rotator cuff repairs at 5 years: part II--prognostic factors for clinical and radiographic outcomes. J Shoulder Elbow Surg. 2011;20:941-946.  [PubMed]  [DOI]
17.  Kim SJ, Kim SH, Lee SK, Seo JW, Chun YM. Arthroscopic repair of massive contracted rotator cuff tears: aggressive release with anterior and posterior interval slides do not improve cuff healing and integrity. J Bone Joint Surg Am. 2013;95:1482-1488.  [PubMed]  [DOI]
18.  Bishop J, Klepps S, Lo IK, Bird J, Gladstone JN, Flatow EL. Cuff integrity after arthroscopic versus open rotator cuff repair: a prospective study. J Shoulder Elbow Surg. 2006;15:290-299.  [PubMed]  [DOI]
19.  Gerber C, Fuchs B, Hodler J. The results of repair of massive tears of the rotator cuff. J Bone Joint Surg Am. 2000;82:505-515.  [PubMed]  [DOI]
20.  Kim HM, Caldwell JM, Buza JA, Fink LA, Ahmad CS, Bigliani LU, Levine WN. Factors affecting satisfaction and shoulder function in patients with a recurrent rotator cuff tear. J Bone Joint Surg Am. 2014;96:106-112.  [PubMed]  [DOI]
21.  Namdari S, Donegan RP, Chamberlain AM, Galatz LM, Yamaguchi K, Keener JD. Factors affecting outcome after structural failure of repaired rotator cuff tears. J Bone Joint Surg Am. 2014;96:99-105.  [PubMed]  [DOI]
22.  Thomazeau H, Boukobza E, Morcet N, Chaperon J, Langlais F. Prediction of rotator cuff repair results by magnetic resonance imaging. Clin Orthop Relat Res. 1997;275-283.  [PubMed]  [DOI]
23.  Goutallier D, Postel JM, Gleyze P, Leguilloux P, Van Driessche S. Influence of cuff muscle fatty degeneration on anatomic and functional outcomes after simple suture of full-thickness tears. J Shoulder Elbow Surg. 2003;12:550-554.  [PubMed]  [DOI]
24.  Burkhart SS, Barth JR, Richards DP, Zlatkin MB, Larsen M. Arthroscopic repair of massive rotator cuff tears with stage 3 and 4 fatty degeneration. Arthroscopy. 2007;23:347-354.  [PubMed]  [DOI]
25.  Gladstone JN, Bishop JY, Lo IK, Flatow EL. Fatty infiltration and atrophy of the rotator cuff do not improve after rotator cuff repair and correlate with poor functional outcome. Am J Sports Med. 2007;35:719-728.  [PubMed]  [DOI]
26.  Fuchs B, Gilbart MK, Hodler J, Gerber C. Clinical and structural results of open repair of an isolated one-tendon tear of the rotator cuff. J Bone Joint Surg Am. 2006;88:309-316.  [PubMed]  [DOI]
27.  Gerber C, Schneeberger AG, Hoppeler H, Meyer DC. Correlation of atrophy and fatty infiltration on strength and integrity of rotator cuff repairs: a study in thirteen patients. J Shoulder Elbow Surg. 2007;16:691-696.  [PubMed]  [DOI]
28.  Chung SW, Kim SH, Tae SK, Yoon JP, Choi JA, Oh JH. Is the supraspinatus muscle atrophy truly irreversible after surgical repair of rotator cuff tears? Clin Orthop Surg. 2013;5:55-65.  [PubMed]  [DOI]
29.  Meyer DC, Farshad M, Amacker NA, Gerber C, Wieser K. Quantitative analysis of muscle and tendon retraction in chronic rotator cuff tears. Am J Sports Med. 2012;40:606-610.  [PubMed]  [DOI]
30.  Kim KC, Shin HD, Kim BK, Cha SM, Park JY. Changes in tendon length with increasing rotator cuff tear size. Knee Surg Sports Traumatol Arthrosc. 2012;20:1022-1026.  [PubMed]  [DOI]
31.  Meyer DC, Wieser K, Farshad M, Gerber C. Retraction of supraspinatus muscle and tendon as predictors of success of rotator cuff repair. Am J Sports Med. 2012;40:2242-2247.  [PubMed]  [DOI]
32.  Tashjian RZ, Hung M, Burks RT, Greis PE. Influence of preoperative musculotendinous junction position on rotator cuff healing using single-row technique. Arthroscopy. 2013;29:1748-1754.  [PubMed]  [DOI]
33.  Carbone S, Gumina S, Arceri V, Campagna V, Fagnani C, Postacchini F. The impact of preoperative smoking habit on rotator cuff tear: cigarette smoking influences rotator cuff tear sizes. J Shoulder Elbow Surg. 2012;21:56-60.  [PubMed]  [DOI]
34.  Galatz LM, Silva MJ, Rothermich SY, Zaegel MA, Havlioglu N, Thomopoulos S. Nicotine delays tendon-to-bone healing in a rat shoulder model. J Bone Joint Surg Am. 2006;88:2027-2034.  [PubMed]  [DOI]
35.  Mallon WJ, Misamore G, Snead DS, Denton P. The impact of preoperative smoking habits on the results of rotator cuff repair. J Shoulder Elbow Surg. 2004;13:129-132.  [PubMed]  [DOI]
36.  Neyton L, Godenèche A, Nové-Josserand L, Carrillon Y, Cléchet J, Hardy MB. Arthroscopic suture-bridge repair for small to medium size supraspinatus tear: healing rate and retear pattern. Arthroscopy. 2013;29:10-17.  [PubMed]  [DOI]
37.  Angeline ME, Ma R, Pascual-Garrido C, Voigt C, Deng XH, Warren RF, Rodeo SA. Effect of diet-induced vitamin D deficiency on rotator cuff healing in a rat model. Am J Sports Med. 2014;42:27-34.  [PubMed]  [DOI]
38.  Abboud JA, Kim JS. The effect of hypercholesterolemia on rotator cuff disease. Clin Orthop Relat Res. 2010;468:1493-1497.  [PubMed]  [DOI]
39.  Beason DP, Tucker JJ, Lee CS, Edelstein L, Abboud JA, Soslowsky LJ. Rat rotator cuff tendon-to-bone healing properties are adversely affected by hypercholesterolemia. J Shoulder Elbow Surg. 2014;23:867-872.  [PubMed]  [DOI]
40.  Bedi A, Fox AJ, Harris PE, Deng XH, Ying L, Warren RF, Rodeo SA. Diabetes mellitus impairs tendon-bone healing after rotator cuff repair. J Shoulder Elbow Surg. 2010;19:978-988.  [PubMed]  [DOI]
41.  Gerber C, Schneeberger AG, Beck M, Schlegel U. Mechanical strength of repairs of the rotator cuff. J Bone Joint Surg Br. 1994;76:371-380.  [PubMed]  [DOI]
42.  Lo IK, Burkhart SS. Double-row arthroscopic rotator cuff repair: re-establishing the footprint of the rotator cuff. Arthroscopy. 2003;19:1035-1042.  [PubMed]  [DOI]
43.  Kim DH, Elattrache NS, Tibone JE, Jun BJ, DeLaMora SN, Kvitne RS, Lee TQ. Biomechanical comparison of a single-row versus double-row suture anchor technique for rotator cuff repair. Am J Sports Med. 2006;34:407-414.  [PubMed]  [DOI]
44.  Smith CD, Alexander S, Hill AM, Huijsmans PE, Bull AM, Amis AA, De Beer JF, Wallace AL. A biomechanical comparison of single and double-row fixation in arthroscopic rotator cuff repair. J Bone Joint Surg Am. 2006;88:2425-2431.  [PubMed]  [DOI]
45.  Meier SW, Meier JD. The effect of double-row fixation on initial repair strength in rotator cuff repair: a biomechanical study. Arthroscopy. 2006;22:1168-1173.  [PubMed]  [DOI]
46.  Meier SW, Meier JD. Rotator cuff repair: the effect of double-row fixation on three-dimensional repair site. J Shoulder Elbow Surg. 2006;15:691-696.  [PubMed]  [DOI]
47.  Grasso A, Milano G, Salvatore M, Falcone G, Deriu L, Fabbriciani C. Single-row versus double-row arthroscopic rotator cuff repair: a prospective randomized clinical study. Arthroscopy. 2009;25:4-12.  [PubMed]  [DOI]
48.  Park JY, Lhee SH, Choi JH, Park HK, Yu JW, Seo JB. Comparison of the clinical outcomes of single- and double-row repairs in rotator cuff tears. Am J Sports Med. 2008;36:1310-1316.  [PubMed]  [DOI]
49.  Lapner PL, Sabri E, Rakhra K, McRae S, Leiter J, Bell K, Macdonald P. A multicenter randomized controlled trial comparing single-row with double-row fixation in arthroscopic rotator cuff repair. J Bone Joint Surg Am. 2012;94:1249-1257.  [PubMed]  [DOI]
50.  Sugaya H, Maeda K, Matsuki K, Moriishi J. Functional and structural outcome after arthroscopic full-thickness rotator cuff repair: single-row versus dual-row fixation. Arthroscopy. 2005;21:1307-1316.  [PubMed]  [DOI]
51.  Charousset C, Grimberg J, Duranthon LD, Bellaiche L, Petrover D. Can a double-row anchorage technique improve tendon healing in arthroscopic rotator cuff repair?: A prospective, nonrandomized, comparative study of double-row and single-row anchorage techniques with computed tomographic arthrography tendon healing assessment. Am J Sports Med. 2007;35:1247-1253.  [PubMed]  [DOI]
52.  Burks RT, Crim J, Brown N, Fink B, Greis PE. A prospective randomized clinical trial comparing arthroscopic single- and double-row rotator cuff repair: magnetic resonance imaging and early clinical evaluation. Am J Sports Med. 2009;37:674-682.  [PubMed]  [DOI]
53.  Mihata T, Watanabe C, Fukunishi K, Ohue M, Tsujimura T, Fujiwara K, Kinoshita M. Functional and structural outcomes of single-row versus double-row versus combined double-row and suture-bridge repair for rotator cuff tears. Am J Sports Med. 2011;39:2091-2098.  [PubMed]  [DOI]
54.  Gartsman GM, Drake G, Edwards TB, Elkousy HA, Hammerman SM, O’Connor DP, Press CM. Ultrasound evaluation of arthroscopic full-thickness supraspinatus rotator cuff repair: single-row versus double-row suture bridge (transosseous equivalent) fixation. Results of a prospective, randomized study. J Shoulder Elbow Surg. 2013;22:1480-1487.  [PubMed]  [DOI]
55.  Kim KC, Shin HD, Lee WY. Repair integrity and functional outcomes after arthroscopic suture-bridge rotator cuff repair. J Bone Joint Surg Am. 2012;94:e48.  [PubMed]  [DOI]
56.  Park JY, Lhee SH, Oh KS, Moon SG, Hwang JT. Clinical and ultrasonographic outcomes of arthroscopic suture bridge repair for massive rotator cuff tear. Arthroscopy. 2013;29:280-289.  [PubMed]  [DOI]
57.  Jost PW, Khair MM, Chen DX, Wright TM, Kelly AM, Rodeo SA. Suture number determines strength of rotator cuff repair. J Bone Joint Surg Am. 2012;94:e100.  [PubMed]  [DOI]
58.  Barber FA, Herbert MA, Schroeder FA, Aziz-Jacobo J, Mays MM, Rapley JH. Biomechanical advantages of triple-loaded suture anchors compared with double-row rotator cuff repairs. Arthroscopy. 2010;26:316-323.  [PubMed]  [DOI]
59.  White CD, Bunker TD, Hooper RM. The strength of suture configurations in arthroscopic rotator cuff repair. Arthroscopy. 2006;22:837-841.  [PubMed]  [DOI]
60.  Düzgün I, Baltacı G, Atay OA. Comparison of slow and accelerated rehabilitation protocol after arthroscopic rotator cuff repair: pain and functional activity. Acta Orthop Traumatol Turc. 2011;45:23-33.  [PubMed]  [DOI]
61.  Kim YS, Chung SW, Kim JY, Ok JH, Park I, Oh JH. Is early passive motion exercise necessary after arthroscopic rotator cuff repair? Am J Sports Med. 2012;40:815-821.  [PubMed]  [DOI]
62.  Lee BG, Cho NS, Rhee YG. Effect of two rehabilitation protocols on range of motion and healing rates after arthroscopic rotator cuff repair: aggressive versus limited early passive exercises. Arthroscopy. 2012;28:34-42.  [PubMed]  [DOI]
63.  Cuff DJ, Pupello DR. Prospective randomized study of arthroscopic rotator cuff repair using an early versus delayed postoperative physical therapy protocol. J Shoulder Elbow Surg. 2012;21:1450-1455.  [PubMed]  [DOI]
64.  Parsons BO, Gruson KI, Chen DD, Harrison AK, Gladstone J, Flatow EL. Does slower rehabilitation after arthroscopic rotator cuff repair lead to long-term stiffness? J Shoulder Elbow Surg. 2010;19:1034-1039.  [PubMed]  [DOI]
65.  Garofalo R, Conti M, Notarnicola A, Maradei L, Giardella A, Castagna A. Effects of one-month continuous passive motion after arthroscopic rotator cuff repair: results at 1-year follow-up of a prospective randomized study. Musculoskelet Surg. 2010;94 Suppl 1:S79-S83.  [PubMed]  [DOI]
66.  Voigt C, Bosse C, Vosshenrich R, Schulz AP, Lill H. Arthroscopic supraspinatus tendon repair with suture-bridging technique: functional outcome and magnetic resonance imaging. Am J Sports Med. 2010;38:983-991.  [PubMed]  [DOI]
67.  Galatz LM, Charlton N, Das R, Kim HM, Havlioglu N, Thomopoulos S. Complete removal of load is detrimental to rotator cuff healing. J Shoulder Elbow Surg. 2009;18:669-675.  [PubMed]  [DOI]
68.  Hettrich CM, Rodeo SA, Hannafin JA, Ehteshami J, Shubin Stein BE. The effect of muscle paralysis using Botox on the healing of tendon to bone in a rat model. J Shoulder Elbow Surg. 2011;20:688-697.  [PubMed]  [DOI]
69.  Gimbel JA, Van Kleunen JP, Williams GR, Thomopoulos S, Soslowsky LJ. Long durations of immobilization in the rat result in enhanced mechanical properties of the healing supraspinatus tendon insertion site. J Biomech Eng. 2007;129:400-404.  [PubMed]  [DOI]
70.  Ide J, Kikukawa K, Hirose J, Iyama K, Sakamoto H, Mizuta H. The effects of fibroblast growth factor-2 on rotator cuff reconstruction with acellular dermal matrix grafts. Arthroscopy. 2009;25:608-616.  [PubMed]  [DOI]
71.  Ide J, Kikukawa K, Hirose J, Iyama K, Sakamoto H, Fujimoto T, Mizuta H. The effect of a local application of fibroblast growth factor-2 on tendon-to-bone remodeling in rats with acute injury and repair of the supraspinatus tendon. J Shoulder Elbow Surg. 2009;18:391-398.  [PubMed]  [DOI]
72.  Hee CK, Dines JS, Dines DM, Roden CM, Wisner-Lynch LA, Turner AS, McGilvray KC, Lyons AS, Puttlitz CM, Santoni BG. Augmentation of a rotator cuff suture repair using rhPDGF-BB and a type I bovine collagen matrix in an ovine model. Am J Sports Med. 2011;39:1630-1639.  [PubMed]  [DOI]
73.  Uggen C, Dines J, McGarry M, Grande D, Lee T, Limpisvasti O. The effect of recombinant human platelet-derived growth factor BB-coated sutures on rotator cuff healing in a sheep model. Arthroscopy. 2010;26:1456-1462.  [PubMed]  [DOI]
74.  Manning CN, Kim HM, Sakiyama-Elbert S, Galatz LM, Havlioglu N, Thomopoulos S. Sustained delivery of transforming growth factor beta three enhances tendon-to-bone healing in a rat model. J Orthop Res. 2011;29:1099-1105.  [PubMed]  [DOI]
75.  Weber SC, Kauffman JI, Parise C, Weber SJ, Katz SD. Platelet-rich fibrin matrix in the management of arthroscopic repair of the rotator cuff: a prospective, randomized, double-blinded study. Am J Sports Med. 2013;41:263-270.  [PubMed]  [DOI]
76.  Rodeo SA, Delos D, Williams RJ, Adler RS, Pearle A, Warren RF. The effect of platelet-rich fibrin matrix on rotator cuff tendon healing: a prospective, randomized clinical study. Am J Sports Med. 2012;40:1234-1241.  [PubMed]  [DOI]
77.  Bergeson AG, Tashjian RZ, Greis PE, Crim J, Stoddard GJ, Burks RT. Effects of platelet-rich fibrin matrix on repair integrity of at-risk rotator cuff tears. Am J Sports Med. 2012;40:286-293.  [PubMed]  [DOI]
78.  Barber FA, Hrnack SA, Snyder SJ, Hapa O. Rotator cuff repair healing influenced by platelet-rich plasma construct augmentation. Arthroscopy. 2011;27:1029-1035.  [PubMed]  [DOI]
79.  Jo CH, Shin JS, Lee YG, Shin WH, Kim H, Lee SY, Yoon KS, Shin S. Platelet-rich plasma for arthroscopic repair of large to massive rotator cuff tears: a randomized, single-blind, parallel-group trial. Am J Sports Med. 2013;41:2240-2248.  [PubMed]  [DOI]
80.  Mazzocca AD, McCarthy MB, Chowaniec DM, Cote MP, Arciero RA, Drissi H. Rapid isolation of human stem cells (connective tissue progenitor cells) from the proximal humerus during arthroscopic rotator cuff surgery. Am J Sports Med. 2010;38:1438-1447.  [PubMed]  [DOI]
81.  Utsunomiya H, Uchida S, Sekiya I, Sakai A, Moridera K, Nakamura T. Isolation and characterization of human mesenchymal stem cells derived from shoulder tissues involved in rotator cuff tears. Am J Sports Med. 2013;41:657-668.  [PubMed]  [DOI]
82.  Gulotta LV, Kovacevic D, Ehteshami JR, Dagher E, Packer JD, Rodeo SA. Application of bone marrow-derived mesenchymal stem cells in a rotator cuff repair model. Am J Sports Med. 2009;37:2126-2133.  [PubMed]  [DOI]
83.  Gulotta LV, Kovacevic D, Packer JD, Deng XH, Rodeo SA. Bone marrow-derived mesenchymal stem cells transduced with scleraxis improve rotator cuff healing in a rat model. Am J Sports Med. 2011;39:1282-1289.  [PubMed]  [DOI]
84.  Mazzocca AD, McCarthy MB, Chowaniec D, Cote MP, Judson CH, Apostolakos J, Solovyova O, Beitzel K, Arciero RA. Bone marrow-derived mesenchymal stem cells obtained during arthroscopic rotator cuff repair surgery show potential for tendon cell differentiation after treatment with insulin. Arthroscopy. 2011;27:1459-1471.  [PubMed]  [DOI]
85.  Kim YS, Lee HJ, Ok JH, Park JS, Kim DW. Survivorship of implanted bone marrow-derived mesenchymal stem cells in acute rotator cuff tear. J Shoulder Elbow Surg. 2013;22:1037-1045.  [PubMed]  [DOI]
86.  Hernigou P, Flouzat Lachaniette CH, Delambre J, Zilber S, Duffiet P, Chevallier N, Rouard H. Biologic augmentation of rotator cuff repair with mesenchymal stem cells during arthroscopy improves healing and prevents further tears: a case-controlled study. Int Orthop. 2014;38:1811-1818.  [PubMed]  [DOI]