Biologics for Accelerated Rehabilitation Following Rotator Cuff Surgery in Athletes

Stephen C. Weber, MD, UNITED STATES Edward G. McFarland, MD, FAAOS, UNITED STATES

ISAKOS eNewsletters   Current Perspective 2025   Not yet rated

History of Biologics

A rotator cuff tear is a common and sometimes debilitating injury of the shoulder. Surgical repair of a rotator cuff tear is indicated when nonoperative treatment fails or is unlikely to adequately restore function (e.g., in high-demand athletes). Demand for lower morbidity, with a quick decrease in postoperative pain and rapid functional recovery within 12 months after shoulder arthroscopy, have accelerated the development of arthroscopic repair techniques. Despite these advances, rehabilitation after arthroscopic rotator repair can be arduous and lengthy. Patient age, tear morphology and size, preoperative stiffness, and muscle weakness have all been described as factors affecting recovery, with Manaka et al. noting that 28% of patients required >6 months to achieve functional recovery¹. In the past 2 decades, orthopedic research has increasingly focused on biologically augmenting the rotator cuff reconstruction in order to accelerate tendon-bone healing. Biological products, as defined by the Food and Drug Administration (FDA), include a wide range of products such as vaccines, blood and blood components, allergenics, somatic cells, gene therapy, tissues, and recombinant therapeutic proteins. Biologics can be composed of sugars, proteins, nucleic acids, or complex combinations of these substances or may be living entities such as cells and tissues. Biologics are isolated from a variety of natural sources—human, animal, or microorganism—and may also be synthesized with use of biotechnology methods and other cutting-edge technologies. There is a 20-year history of biological augmentation in rotator cuff repair which has included applying different platelet concentrates containing growth factors, mesenchymal stem cells (MSCs), scaffolds and different combinations of the above. The benefits of augmentation become especially valuable to athletes.

The Concept

Tendon-to-bone healing is a multi-stage process, and while it naturally progresses over time, several strategies can accelerate this process. These strategies include the use of biological therapies such as growth factors and stem cells. Tendon-to-bone healing involves three main phases:

• Inflammatory phase: This initial phase, lasting about a week, involves clot formation and the arrival of inflammatory cells to stabilize the injury.
• Proliferative phase: This phase, occurring from 1 to 4 weeks, is characterized by the synthesis of new collagen and other extracellular matrix components by tenocytes.
• Remodeling phase: Starting around 4 weeks, this phase focuses on organizing and strengthening the new tissue, with collagen fibers aligning along the lines of stress. Osseous integration of this interface appears to happen via progressive ossification of the extracellular matrix².

A key point in tendon-to-bone healing is the modulation and regulation of collagen production in phase II. A primary role in this process belongs to growth factors, notably insulin-like growth factors-I and II (IGF-I and II), transforming growth factor β (TGFβ), vascular endothelial growth factor (VEGF), platelet-derived growth factor (PDGF), and basic fibroblast growth factor.² However, histological studies of animal models have demonstrated a lack of the normal transition zones in the healed tendon-to-bone interface and instead have shown the formation of scar tissue between tendon and bone, likely conferring inferior mechanical properties. Biologic augmentation has been directed at accelerating this process of healing and improving the mechanical properties of the resulting tendon-bone interface.

Results

Several review articles have provided an excellent overview of the current status of biologic augmentation of rotator cuff repair³. Although biologic augmentation has been associated with improved rates of tendon-to-bone healing, data on the acceleration of healing following rotator cuff repair are more limited.

Rodeo et al. investigated the implantation of bone morphogenetic protein (BMP)-2 to BMP-7, transforming growth factor TGF-β1 to TGF-β3, and fibroblast growth factor with use of a collagen type-I sponge between the tendon and the footprint4. After 6 and 12 weeks, an increased maximum load to failure was noted. Those authors concluded that a mixture of the implanted cytokines accelerates the healing process but does not change the quality of the repair. Seehermann et al. described similar results in a study of the use of BMP-12 or TGFb4 in isolation in animal models. Rodeo et al. stated that no data are available regarding the use of these factors for rotator cuff healing in humans4.

Platelet-rich plasma (PRP) also has been explored as a means to accelerate healing as it contains many of the factors that might be assumed to affect healing. However, Jo et al. reported no difference in healing rates between patients who had been managed with or without leukocyte-poor PRP gel preparation at the time of rotator cuff repair⁵. Similarly, other studies have shown that postoperative image-guided PRP treatments did not improve early tendon-bone healing. Current reviews have indicated that PRPs may not necessarily accelerate healing.

Cell-based augmentation with use of embryonic stem cells, multipotent stem cells, or adult stem cells also has been considered. The most frequently investigated augmentation method involves the use of mesenchymal stromal cells (MSCs) sourced from adipose tissue or bone marrow. While some reports have described the preliminary results of cell-based augmentation to improve healing following rotator cuff repair, the current literature does not include any data on the use of cell-based augmentation to accelerate healing.

Scaffolds represent another avenue for accelerated healing. Scaffold options include allografts, xenografts, and synthetic scaffolds. Although providing a biologic splint to protect the healing interface might seem especially promising, the results o a recent bovine bioinductive collagen implant did not show improved functional outcomes at any time point. Inflammatory responses to xenografts remain problematic, and better outcomes generally have been obtained with allografts. Similar to the results achieved with cell-based augmentation, final healing of the repair has been improved in some studies, but the acceleration of healing, either due to improved biology or the scaffold’s ability to splint and so protect the repair, has not been demonstrated.

Conclusion

The current literature remains inconclusive with regard to the use of orthobiologics to accelerate the healing of rotator cuff repairs. Although animal studies have suggested that growth factors may have some role in accelerated healing, 2 prospective, randomized studies failed to show any accelerated healing using PRP. While promising, the acceleration of healing with scaffolds or cell-based augmentation has not been described. The acceleration of rotator cuff repair using biologics in athletes appears to remain elusive.

References

1. Manaka T, Ito Y, Matsumoto I, Takaoka K, Nakamura H. Functional recovery period after arthroscopic rotator cuff repair: is it predictable before surgery? Clin Orthop Relat Res. 2011 Jun;469(6):1660-6. doi: 10.1007/s11999-010-1689-6. Epub 2010 Nov 24. PMID: 21107925; PMCID: PMC3094637.
2. Bunker DL, Ilie V, Ilie V, Nicklin S. Tendon to bone healing and its implications for surgery. Muscles Ligaments Tendons J. 2014 Nov 17;4(3):343-50. PMID: 25489553; PMCID: PMC4241426.
3. Anz AW, Hackel JG, Nilssen EC, Andrews JR. Application of biologics in the treatment of the rotator cuff, meniscus, cartilage, and osteoarthritis. J Am Acad Orthop Surg. 2014 Feb;22(2):68-79. doi: 10.5435/JAAOS-22-02-68. PMID: 24486753.
4. Rodeo SA, Potter HG, Kawamura S, Turner AS, Kim HJ, Atkinson BL. Biologic augmentation of rotator cuff tendon-healing with use of a mixture of osteoinductive growth factors. J Bone Joint Surg Am. 2007 Nov;89(11):2485-97. doi: 10.2106/JBJS.C.01627. PMID: 17974893.
5. Jo CH, Kim JE, Yoon KS, Lee JH, Kang SB, Lee JH, Han HS, Rhee SH, Shin S. Does platelet-rich plasma accelerate recovery after rotator cuff repair? A prospective cohort study. Am J Sports Med. 2011 Oct;39(10):2082-90. doi: 10.1177/0363546511413454. Epub 2011 Jul 7. PMID: 21737832.

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