Contemporary rotator cuff repair surgery can trace its lineage via a series of innovations. Codman first described rotator cuff disease in 1934 and established repair as a treatment concept.1 In the 1960s Neer advanced the pathomechanics of subacromial impingement and open subacromial decompression as part of rotator cuff repair treatment.2 Considered standard practice today, arthroscopic repair was pioneered by Burkhart and Snyder in the 1980s.3, 4 As arthroscopic rotator cuff repair technique evolved, strategies to improve healing rates were developed in tandem with increasing understanding of the factors that contribute to healing, for example, margin convergence and medialization to decrease tension. Biomechanically robust suture and anchor-based constructs were developed. Biomechanical studies comparing double row techniques to simple single row techniques have reported superior footprint restoration and biomechanical stability for double row constructs.5, 6, 7, 8, 9, 10, 11, 12, 13 However, clinical outcomes are comparable.13 The SCOI Row has been shown to have superior biomechanical performance to a double row construct.14

Recent literature has identified features that contribute to rotator cuff failure to heal with surgical repair. Mechanical factors such as tendon retraction, poor tissue quality, muscle atrophy, and fatty infiltration all have been implicated in preventing adequate healing from tendon to bone and impairing muscle function postoperatively.15, 16, 17 Robust modern rotator cuff repair constructs provide far beyond adequate biomechanical fixation.18,19 However, the biologic environment of the rotator cuff is often compromised due to decreased tendon vascularity and cell viability which can also contribute to the lack of healing potential.20,21 This challenge is further compounded by patient related factors such as tear chronicity, patient age, and comorbidities, all of which can lead to suboptimal outcomes and increase the failure rate.22 While many studies have reported on the failure rate after RCR, the results continue to vary widely, with retear rates ranging from 10 to 94%23 with a tendency to increase with longer follow-up durations. A recent MRI study reported at 1-2 years of follow up retear rate was 33%, with re-tear associated with fatty infiltration and preoperative tear size.24

Thus, there has been increasing emphasis on the biology of healing, as healing is increasingly understood to correlate with functional outcomes, and healing success may be dependent on a form of augmentation during the time of the index surgery.25 The Rotator Cuff Healing Index (RoHI) score was developed by Kwon et al in 201925 to estimate the likelihood of tendon healing following rotator cuff repair. It assigns points based on age, anteroposterior tear size, tendon retraction, infraspinatus fatty infiltration, bone mineral density, and work activity level. Higher scores indicate a higher risk of failure and many surgeons have adopted this score into decision making when considering whether to use additional biologic or mechanical augmentation during rotator cuff repair.26 Likewise biomaterials for sutures and anchors are increasingly tailored to supporting biological tendon to bone healing and incorporation. Biologic augments include platelet rich plasma (PRP), cell-based therapies, and bursal tissue autograft. These are often placed in the subacromial space at the time of rotator cuff repair. Bioinductive implants have been used as augmentation during rotator cuff repair to provide a scaffold for collagen formation. Some biointegrative implants also provide structural support. Human dermal allografts can also be used reinforce repair or bridge tendon defects when native tissue is insufficient. The long head of the biceps tendon (LHBT) has emerged as a viable autograft option for augmenting rotator cuff repair as well. Increased attention has also come to the role of medical and nutritional optimization. The purpose of this article is to review recent innovations in rotator cuff repair including biomaterials. biologics, bioinductive scaffolds, structural and mechanical augmentation, and nutritional optimization, and to preview future directions.

With the current focus on biological healing, ongoing efforts are being undertaken to refine repair constructs to support healing. Stress concentration of suture anchor-based rotator cuff repairs is particularly pronounced at the tendon–bone interface and the suture–tendon junction, areas commonly associated with repair failures.27

Cummins et al reported that most revision rotator cuff repairs using suture anchors failed at the tendon–suture interface, highlighting it as a critical weak point in rotator cuff repair.28 Correspondingly there has been a focus on developing enhanced suture materials. A novel collagen co-braid of type I collagen and ultra-high molecular weight polyethylene has been developed as collagen may encourage angiogenesis and tissue formation.

A study showed that collagen co-braids provide sufficient mechanical properties for the high demands of orthopaedic procedures while incorporating a biological component.29 Cell-Assembled extracellular Matrix (CAM) is a biological suture synthesized from mesenchymal cells. A recent study introduced CAM-based biological sutures, demonstrating favorable mechanical properties in vascular surgery. These sutures also show promise and potential in musculoskeletal care.30 A dynamic self-tensioning suture loop length decreases by 27% after encountering fluid, however, patient-reported outcomes did not differ significantly between the dynamic tensioning and static tensioning sutures.31,32

Modern biocomposite anchors incorporate materials such as beta-tricalcium phosphate to enhance osteoconductive and osteoinductivity while maintaining controlled degradation. These advances allow better bone integration than was possible with metal anchors and minimize complications such as osteolysis or cyst formation while still ensuring adequate fixation during the healing process.33,34 All-suture anchors offer bone preservation and are easier to deal with in revisions, and have comparable clinical outcomes to solid anchors.35 Chitosan quaternary ammonium salt–coated Nickel-Titanium Memory Alloy Anchors (NTMA) anchors show enhanced fixation strength and promoted local osteogenesis during osteoporotic rotator cuff repair, suggesting that the use of these anchors facilitates the repair of rotator cuff injuries in osteoporotic bones.36Multiple studies show that cement augmentation of suture anchors improves pullout strength regardless of cement type used or anchor position.37

Modern suture anchors have also been increasingly designed with vents to maximize the biological effect of elution of marrow elements that occurs with anchor placement, and there are recent efforts underway from industry to improve the environmental footprint of implant production and implantation.

Successful postoperative healing of the rotator cuff is influenced by vascularity, the condition of the bursa, and the health of the bone and muscle-tendon unit. Healing outcomes are further influenced by both intrinsic and extrinsic factors. Intrinsic factors include systemic conditions such as diabetes and, as well as biological conditions such as patient age. Extrinsic factors include diet, tobacco abuse, rehabilitation adherence, and mechanical loading during recovery. Biological augments are intended to optimize the healing environment at the repair site and complement mechanical stability. Cell based therapies have been shown to promote cellular proliferation, angiogenesis, and tissue regeneration and enhance the tendon-to-bone healing process. Bono et al showed that Approximately 83% of preclinical studies found a positive biomechanical or histological effect, with no studies showing an overall negative effect.38

Currently available augments include local marrow stimulation, platelet rich plasma (PRP), adipose-derived stem cells (ADSCs), autologous dermal fibroblast, Bone marrow aspirate concentrate, and growth factors (GFs).

An element of Snyder’s SCOI Row repair, marrow venting of the humerus creates a “crimson duvet” (Fig. 1), a biologic clot or blanket, of growth factors and medicinal signaling cells which bathes the tendon-bone repair interface.39 He et al reported that SCOI Row including marrow stimulation helped regenerate the tendon enthesis as seen on follow up magnetic resonance imaging.40 A meta-analysis of 5 randomized controlled trials and 4 cohort studies with a total of 827 patients found that the pooled retear rate between the RCR with marrow venting group and the RCR alone group was significantly different (17.5% vs. 28.9%; P < 0.0001. Analysis further found that RCR with venting resulted in a significantly lower retear rate than RCR alone for large and massive RCTs (19.7% vs. 32.5%; P = 0.01).41 Another meta-analysis found that the healing rates of rotator cuff repair were similar between the 2 groups (ie, with and without venting) (odds ratio, 1.58 [95% CI, 0.63-4.00]; P = .33). Though not statistically significant this data trended in favor of BMS with the OR of 1.58 for healing.42 A systematic review and meta-analysis found that the pooled retear rate across all 9 clinical studies for patients undergoing marrow stimulation was 11%. For the 5 studies in the meta-analysis, the pooled retear rates were 15% for marrow stimulation and 30% for controls. Meta-analysis demonstrated a significant difference in the overall retear rate that favored marrow stimulation (odds ratio [OR], 0.41; 95% CI, 0.25-0.66; P = .0003; I 2 = 0%). Similarly, meta-analysis of the Constant score at final follow-up demonstrated a statistically significant difference between the 2 groups that favored a higher Constant score in the marrow stimulation group (mean difference, 2.84; 95% CI, 1.02-4.66; P = .002; I 2 = 29%).43 Greater tuberosity marrow stimulation is an efficient and cost-effective way to support rotator cuff repair healing.

Platelet Rich Plasma (PRP) provides a rich source of GFs and cytokines such as PDGF, TGF-β, FGF, VEGF, and IGF. In a study comparing the clinical and structural outcomes between arthroscopic repair of full thickness rotator cuff tears with and without PRP supplementation, retear rates were lower with PRP in tears greater than 3 cm, with improved Constant score.44

Jo et al conducted a randomized controlled trial to evaluate the effect of PRP on retear rates following arthroscopic repair of large to massive rotator cuff tears. At a minimum follow-up of 9 months, the retear rate in the PRP group (20%) was significantly lower than that in the conventional group (55.6%).45 Li et al published a review of 23 RCTs with 1440 patients, showed PRP resulted in significantly decreased rates of retear (15.9% versus 29.0%, respectively; P < .0001) and improved functional outcome scores.46 Conversely, platelet-rich fibrin clot matrix, a variant of PRP with a fibrin matrix showed no difference in tendon thickness and greater tuberosity coverage in chronic full tears, and positive outcomes in partial tear. Future research should focus on defining PRP formulations and identifying patient and tear characteristics to optimize its efficacy.

ADSCs have a comparable shape and expression of the cluster differentiation surface marker protein to Bone Marrow Stem Cells (BMSCs) with greater colony-forming and adipogenic capacity. They demonstrated multipotency in-vitro; developing into adipose, osteogenic, chondrogenic, and myogenic cells. A study in rabbits showed improved load to failure and less fatty infiltration for a suture and ADSC group compared to a suture and group. Moreover, ADSCs imbedded in a fibrin sealant resulted in superior histological and biomechanical outcomes, in acute full murine RC repairs. Regeneration was found most effective when stem cell sheets were interposed at the enthesis, in chronic full tears.47, 48, 49, 50, 51

By contrast, ADSCs in acute and chronic rat RC repair models did not enhance biomechanical characteristics. However, inflammation was reduced, which could potentially lead to a more elastic repair and less scar formation after the healing process. Furthermore, TGF-β3 supplementation did not enhance ADSCs’ effect on healing, despite its known role in the development of the enthesis. Randelli et all showed in a prospective randomized controlled trial that the intraoperative injection of autologous microfragmented adipose tissue is safe and effective in improving short-term (up to 6 months) clinical and functional results after single-row arthroscopic rotator cuff repair.52 Dermal fibroblasts may be a promising cell source for tendon engineering because they are easily accessible and exhibit multiple similarities to tendon cells. Recent studies have proven that dermal fibroblasts hold therapeutic potential and are attractive for rebuilding injured tendons based on their tenogenic differentiation potential in vitro, in vivo, and in clinical applications. A randomized controlled trial recently reported that repairs augmented with cultured ADFs had significantly lower retear rate (5.6% [2/36]) than in the control group (24.3% [9/37]) (P = .025).53 Bone marrow aspirate concentrate contains high concentrations of platelets, MSCs, and progenitor cells, which may support tissue healing. In a case-control study comparing 45 patients who received bone marrow concentrate during rotator cuff repair to 45 patients who underwent standard repair, 100% of treated repairs had healed by 6 months, with 87% remaining intact at 10 years, compared with 66% healed and 44% intact in the standard repair group.54 Schoch et al reported that in a study comparing 3800 patients who did not receive biologic augmentation during rotator cuff repair to 646 patients who received PRP and 114 patients who received bone marrow aspirate concentrate (BMAC), those who received BMAC showed significantly lower 2-year revision rates compared with both the PRP cohort and the control.55 An animal study suggests BMAC may be combined with other GFs to enhance mechanical strength and histological healing at the tendon-bone junction.56 However, clinical studies are limited, and further research is needed to fully understand the effectiveness of BMAC.57

GFs such as fibroblast GF (FGF), transforming GF β3 (TGF-β3), bone morphogenic proteins (BMPs), and platelet-derived GF have shown promise in enhancing animal model rotator cuff enthesis healing by stimulating stem cell activity and tissue formation, particularly in the early stages of healing. FGFs and BMPs aid in angiogenesis and cell proliferation, key processes in regenerating tissue structure. In addition, combining TGF-β3 with other cytokine inhibitors may reduce fibrosis and improve tissue organization, promoting a regenerative rather than a scar-driven healing process.58Demineralized bone matrix (DBM), PRP, and BMAC each contribute unique properties that may improve enthesis healing. DBM may do so by supporting mesenchymal stem cell (MSC) adhesion, proliferation, and differentiation, especially when combined with PRP or bone marrow stem cells, improving chronic rotator cuff tears. However, DBM alone has shown inconsistent outcomes in terms of collagen organization, fibrocartilage formation, and bone mineral density improvement.59 GFs have been investigated to modulate stem cells in RC enthesis of small and large animal models. Fibroblast growth factor 2 (FGF-2), growth differentiation factor, TGF-β3, and platelet-derived growth factor are commonly used examples. GFs such as BMP-12, -13, -14, basic fibroblast growth factor, cartilage oligomeric matrix protein, connective tissue growth factor, platelet-derived growth factor-B, and TGF-β1 have been found to be involved in enthesis healing process 1 week after acute full rat supraspinatus repair, indicating that exogenous supplementation of these substances may encourage successful healing in acute stages.60 Although frequently having superior mechanical properties compared to controls, GF-enhanced repairs lack identical biomechanical qualities as native entheses.61

Indian Hedgehog (Ihh) signaling is active during the initial phases of RC enthesis healing.62 Fibrocartilage production in an acute full rat RC repair model had higher numbers of Ihh chondrocyte-like cells with MSC augmentation. Increased GLI family zinc finger 1 (Gli1) and Patched1 expression suggests that Ihh signaling pathway controls fibrocartilage production process brought on by stem cells. While both are expressed in fibroblasts of the tendon mid-substance, Ihh is primarily expressed in chondrocytes of the fibrocartilage region, which may indicate a coordinated interaction between chondrocytes and fibroblasts during healing. Parathyroid hormone (PTH) has been demonstrated to enhance tissue repair via a chondrogenic pathway.63,64 Osteoblasts speed up tendon-bone healing when PTH binds to its receptor in BMSCs during the tendon-bone healing process. Chen et al showed that PTH may influence the tendon-bone healing process by maintaining the proliferation of BMSCs. Daily systemic PTH injections boosted fibrocartilage development, type-I procollagen-producing cells, and vascularity, which improved collagen fiber structure and mineralized fibrocartilage production in acute full RC tears.65 Biomechanically, Duchman et al reported higher load to failure in recombinant human PTH-treated acute full RC tear rat model, and expression of intracellular and extracellular vascular endothelial growth factor (VEGF) with controlled recombinant human PTH systemic injections.66 Clinical investigations of advanced cases with chronic large tears achieved similar outcomes, and reduced retear rates. Oh et all showed the rate of retear was significantly lower in the rPTH group than control group (16% vs 33.9%; P = .04).67 Further work remains to be done to develop these promising targeted therapeutic interventions to bring them into mainstream clinical practice.