Animal models for study on rotator cuff healing

Abstract

Rotator cuff tears are highly prevalent, and there is an urgent need to understand their healing mechanisms to improve treatment outcomes for patients. This editorial aims to summarize the roles and limitations of common animal models (including rodents, rabbits, sheep, dogs, and primates) and second-look arthroscopy in rotator cuff healing research. Different animal models offer distinct advantages and disadvantages. For example, rodent models are cost-effective and suitable for genetic studies but have anatomical differences from humans. Rabbit models are favored for their relatively large tendon size and ease of surgical manipulation, yet they still deviate from human shoulder anatomy in some aspects. Larger animals like sheep and dogs have more similar shoulder structures to humans but come with high costs and challenges in maintaining consistent experimental conditions. Second-look arthroscopic studies have provided evidence for the effectiveness of current surgical techniques. Animal models will continue to play a crucial role in further exploring the local microenvironment of the rotator cuff, which is expected to help develop more effective strategies to promote healing.

Key Words: Animal model; Rotator cuff; Arthroscopic repair; Tendon-bone healing; Second-look arthroscopy

Core Tip: Animal models are crucial tools for studying rotator cuff healing. Different models, including rodent, rabbit, and large-animal models, offer distinct advantages, such as cost-effectiveness, ease of genetic manipulation, or anatomical similarity. However, they also have limitations like anatomical disparities and high costs. These models help in understanding the repair mechanisms and evaluating new treatments. Second-look arthroscopic studies support the effectiveness of current surgical procedures, and future research using animal models can focus on the local microenvironment of the rotator cuff to enhance healing.

INTRODUCTION

The study of rotator cuff healing is of great significance as rotator cuff injuries are common and can severely impact patients' quality of life. The article by Yiannakopoulos et al[1] published in the recent issue of the World Journal of Orthopedics uses second-look arthroscopy to evaluate soft tissue healing after arthroscopic repair of rotator cuff tears or shoulder instability in 24 patients. Results show nearly all patients achieved complete healing at tissue reattachment sites, with the strongest repair at suture passage areas; clinical scores significantly improved postoperatively, and bioabsorbable implants caused no adverse reactions. However, second-look arthroscopy is an invasive procedure, primarily performed in this study for unrelated clinical issues rather than routine healing assessment, limiting its proactive research utility.

ANIMAL MODELS IN ROTATOR CUFF HEALING RESEARCH: CONTRIBUTIONS, LIMITATIONS, AND THE ROLE OF SECOND-LOOK ARTHROSCOPY

Animal models have long been used as indispensable tools in this area of research[2]. Rodent models, especially rats, are frequently employed. Rats are relatively inexpensive, and there is a wealth of knowledge regarding their biology. They have been used to study pathological changes associated with rotator cuff injuries. For example, they are useful in exploring factors affecting tendon-to-bone healing, such as the role of cells, the preparation of the footprint area, and the influence of growth factors and hormones. However, the small size of the rat shoulder joint and its anatomical differences from the human shoulder make surgical procedures extremely challenging. The rat shoulder has a different structure from that of a human, with the supraspinatus muscle passing under the acromion rather than the tendon. This anatomical variation may limit the direct translation of animal findings to human medicine. Additionally, postoperative observation is difficult because of their small size[3].

Conversely, mice convey a unique advantage in genetic research. They can be genetically modified through gene-knockout techniques, allowing researchers to study the roles of specific signal transduction pathways and molecules related to tendon degeneration and repair. In vivo molecular imaging can also be performed using mice, providing real-time information on biological processes during rotator cuff healing[4].

Rabbit models have gained popularity for rotator cuff research. Compared with that in rodents, the tendon size in rabbits is relatively larger, rendering surgical operations more feasible[5,6]. The supraspinatus, infraspinatus, and subscapularis tendons have been used to create rotator cuff injury models. In particular, the subscapularis tendon of rabbits has similar anatomical and biomechanical characteristics to that of humans in some aspects, making it suitable for studying muscle changes such as atrophy and fatty infiltration after rotator cuff injury. Rabbit models are also commonly used to observe the therapeutic effects of various growth factors and tissue engineering materials on rotator cuff injuries. However, rabbit shoulder anatomy still does not perfectly mimic that of humans. For example, the supraspinatus in rabbits runs above the acromion instead of passing under it, as in humans.

Sheep and dogs are large animal models. The shoulder joint anatomy of these animals is more similar to that of humans, which is beneficial for studying rotator cuff repair[7]. However, their quadrupedal locomotion pattern is quite different from that of bipedal human movement. After modeling, long-term weight-bearing and walking of the forelimbs can affect the healing of rotator cuff injuries, making it difficult to ensure the consistency of the experimental results. Moreover, these animals have a long growth cycle and high experimental costs, which restricts their large-scale use in research[8]. Recent studies have further confirmed muscle atrophy and fatty infiltration after acute repair in sheep, supporting the idea that large animal shoulders resemble those of humans but that quadruped loading affects healing[9].

Although primates have the most similar shoulder anatomy to humans, ethical concerns, high breeding costs, and management difficulties limit their use in experimental studies. Second-look arthroscopic studies are important for evaluating the outcomes of rotator cuff repair. These studies have shown good surgical results, providing evidence for the effectiveness of current surgical techniques. For example, researchers can directly observe the repaired rotator cuff tissue, evaluate the degree of tendon-to-bone healing, and detect any possible complications. The stronger repair at the suture passage areas is attributed to the stress distribution at the fibro-osseous junction due to the suture tunnel, which enhances the stability of the repair.

CONCLUSION

Animal models are essential for the study of rotator cuff healing. Despite their limitations, they have provided valuable insights into the mechanisms of rotator cuff injury and repair. Various models, from rodents to large animals, contribute to our understanding in different ways. Second-look arthroscopic studies have validated the effectiveness of surgical treatments to some extent. In the future, animal models can be further exploited to study the local rotator cuff microenvironment. By understanding factors such as the extracellular matrix, cell-cell interactions, and the role of inflammatory mediators in the local microenvironment, we can develop more effective strategies to promote rotator cuff healing and improve treatment outcomes for patients suffering from rotator cuff injuries.