Animal models used in meniscal repair research from ex vivo to in vivo: A systematic review

Abstract

This systematic review, registered with Prospero, aims to identify an optimal animal model for meniscus repair research, moving from ex vivo experimentation to in vivo studies. Data sources included PubMed, Medline, all Evidence-Based Medicine Reviews, Web of Science, and Embase searched in March 2023. Studies were screened using Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Extracted data including animal model, type of experiment, type of tear, surgical techniques, and measured outcomes, were recorded, reviewed, and analyzed by four independent reviewers. The SYstematic Review Centre for Laboratory animal Experimentation (SYRCLE) Rob tool was used for critical appraisal and risk of bias assessment. Out of 11,719 studies, 72 manuscripts were included for data extraction and analysis; 41 ex vivo extra-articular studies, 20 ex vivo intra-articular studies, and only 11 in vivo studies. Six animal models were employed: porcine, bovine, lapine, caprine, canine, and ovine. Longitudinal lesions were the most frequently studied tear pattern and sutures the most common repair technique. Studied outcomes focused mainly on biomechanical assessments and gross observations. This systematic review can guide researchers in their choice of animal model for meniscus repair research; it highlighted the strengths of the porcine, caprine, and bovine models for ex vivo cadaveric studies, while the porcine and caprine models were found to be more suited to in vivo studies due to their similarities with human anatomy. Research teams should familiarize themselves with the advantages and disadvantages of various animal models before initiating protocols to improve standardization in the field.

1. Introduction

Meniscectomy remains the most commonly performed meniscal surgery.¹ However, while quick and effective in the short to mid-term, this procedure leads to early onset osteoarthritis.² Consequently, a paradigm shift to “save the meniscus” recently occurred, leading to several novel meniscus repair techniques,^3,4 but these advances are limited by the type of tear and the poor vascularization of the meniscus.⁵ Additionally, meniscus repair is not universally applicable; it is more technically intricate, time-consuming, and costly in terms of equipment,^5,6 with a success rate between 60% and 90%, depending on the type of tear.⁷ The imperative to develop innovative and effective repair techniques becomes apparent when considering the limited treatment options and the prevalence of meniscus injuries.⁸ The process to develop new surgical technologies is gradual and begins with cadaveric animal laboratory studies, followed by proof-of-concept investigations paving the way for subsequent in vivo animal studies.⁹ Cadaveric (ex vivo) animal studies are particularly useful to test, optimize, and assess the safety and efficacy of novel approaches, as well as the biomechanics involved.¹⁰ Meanwhile, in vivo animal studies explore short and long-term biological responses and can assess biomechanical data after sacrifice.¹¹ They also provide information on the toxicity and potential side effects of the products used, which is crucial for health authority approval.⁹ Unfortunately, no guidelines are currently available to select animal models in meniscal repair research, as opposed to knee cartilage repair for example.¹² Bansal et al. provide the only systematic review of the broad range of animal models used in meniscal repair research. They aptly identify the need for guidelines and a standardized research approach to improve the reproducibility, comparability, translation, and validity of experiments.¹¹ The aim of this systematic review was to identify the various animal models used in meniscal repair research, ranging from cadaveric studies to in vivo experiments. This information can then guide researchers throughout the development of new meniscal repair approaches and contribute to the standardization of future studies. The hypothesis was that some cadaveric and in vivo models are more relevant for this type of research due to anatomical, biological, translational, and practical reasons.

2. Material and methods

2.1. Search strategy

This systematic review was registered in PROSPERO (CRD42022345839) and followed the Preferred Reporting Items for Systematic Review and Meta-Analysis Protocols PRISMA checklist. Searches of the PubMed, Ovid Medline, Ovid All Evidence-Based Medicine (EBM) Reviews, Ovid Embase and Web of Science databases were completed by the institution's librarian specializing in literature searches in March 2023. There were no publication date restrictions and results were limited to English or French language studies. Using Covidence, we included studies that assessed an animal model(s) used for meniscus repair. Studies consisting exclusively of human, in vitro or in silico models, along with meniscal interventions other than repair (meniscal allograft, transplant, prosthesis, cartilage only studies, osteoarthritis models, etc), systematic reviews, meta-analysis, anatomopathological only studies, ophthalmology studies, veterinarian studies, editorials and expert opinions were excluded. The complete search strategy is outlined in Appendix 1.

A total of 20,476 citations were retrieved from the five databases. After removing duplicates, four independent researchers screened the 11,719 remaining studies. A senior author was available to settle any disagreements. First, titles and then abstracts were screened before performing a complete review of the selected manuscripts. The full texts of these potentially eligible studies were retrieved and independently assessed for eligibility by two authors, a third author resolved any discrepancies.

2.2. Study selection, data extraction and analysis

A standardised data extraction template was designed prior to manuscript review to extract relevant data from the selected studies. Categories were established to assess the characteristics of the animal meniscus and repair method, with a focus on its comparability with the human meniscus (i.e., similar anatomy and physiology). The advantages and disadvantages of each animal model were also noted. Study descriptors, when available, were included: animal size (large or small), animal type, meniscus anatomy and similarity to the human meniscus, surgical use (ex vivo extra-articular, ex vivo intra-articular, or in vivo), type of tear, repair technique, outcomes (histological, macroscopic, biomechanical, genetic analysis, arthroscopic, imagery, etc.), advantages (price, size, handling ease, level of care, etc.) and disadvantages. Animals rabbit size and smaller were categorized as small animals and those remaining as large animals. The following factors were also considered: cost, ethics and regulations, as well as practical considerations such as housing, feeding, and the need for trained personnel. Extracted data were synthesised using standard statistical methods. Data on animal distribution, experimental design, type of tear, surgical technique and devices, as well as outcomes were compiled with Microsoft Excel (Microsoft Corporation 2018).

2.3. Critical appraisal of evidence and risk of bias for animal studies

The SYstematic Review Centre for Laboratory Animal Experimentation (SYRCLE) was used to assess the quality and risk of bias.¹³ This tool comprises 10 items, addressing six types of bias but is not meant to provide a score or overall calculation. Instead, it functions as an evaluation tool, categorizing the risk of bias as low, high, or unclear. Assessments were conducted by two independent reviewers. Animal studies do not allow for the use of scores commonly employed in research on human patients. The SYRCLE tool is an adaptation of the Cochrane Risk of Bias tool.

3. Results

From the 11,719 studies initially identified for this systematic review, 737 manuscripts were deemed eligible for full-text review after screening titles and abstracts. Subsequently, 665 studies were excluded because they did not meet the inclusion criteria. Indeed, several in vivo studies used meniscal tears as a means to induce osteoarthritis rather than focusing on meniscal repair. Ultimately, a total of 72 studies were included for comprehensive data analysis, as presented in the PRISMA flowchart (Fig. 1).

Fig. 1.

PRISMA Flow diagram.

There were only six animal models for meniscal repair: porcine, bovine, lapine, caprine (goats), canine, and ovine (sheep). The studies reported on a total of 3603 animal menisci, distributed as follows: 58.7% porcine, 24% bovine, 6.7% lapine, 5.4% caprine, 4.1% canine, and 1.4% ovine. Large animals were significantly more common than small animals (93.3% vs. 6.7%) (Fig. 2). There was a noticeable increase in the porcine model in the early 2010s, coinciding with a decrease in the bovine model during the same period.

Fig. 2.

Animal distribution.

3.1. Animal model characteristics

3.1.1. Porcine model

Thirty-six studies used the porcine model which had anatomical properties comparable to that of human menisci. Specifically, similarities were reported in terms of size, function, vascularization, healing potential, cell density, cartilage thickness, and collagen structure, especially for the posterior medial root attachment.14, 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39 Cadaveric porcine models are often readily available and low cost for research laboratories since they can be provided by the food industry.19, 20, 21, 22^,24, 25, 26^{,30,32,34,35,37,38,}40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53 As farm animals, porcine models are widely accessible in vivo, although their maintenance poses additional challenges. Pigs are relatively expensive (approximately $260 for the animal itself, $250 for minor surgery, and $5 per diem), challenging to house, and can be aggressive, making post-operative care demanding.²⁸ Additionally, pigs cannot fully extend their knees (extension around 40°), have a small notched protrusion at the junction of the lateral meniscal body with the posterior horn and an intra-articular flexor hallucis longus (FHL).^15,29,54

3.1.2. Bovine model

The mechanical properties and orientation of the collagen fibrils of the bovine meniscus were found to be similar to those of humans. Histologically, the properties of bovine menisci closely resemble those of humans, with notable differences. Lack of full extension with wider and thicker menisci. Additionally, the lateral meniscus is longer than that in the human knee, and an intra-articular FHL is present.^18,29,55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69 It is worth noting that there have been no bovine in vivo studies, but this model is suitable for ex vivo studies and readily available as a by-product of the food industry.^56,62,66,67

3.1.3. Caprine model

Two studies on caprine menisci discussed their similarities to the humans’. When it comes to purely anatomical considerations, the viscoelastic properties, medial meniscus, lateral meniscus and anterior cruciate ligament were found to be the most comparable to human menisci,^27,29 with a similarly limited intrinsic healing capacity.^27,29 Goats can stand on their two hind legs, but also lack full extension, with extension and flexion angles ranging from 40° to 145°.²⁹ Goat menisci are smaller in size but significantly thicker than human menisci. Similarly to other models, an intra-articular FHL is also present.^70,71 The caprine model is the most used for in vivo studies, second to the lapine model. Goats are relatively easy to obtain when mature, gentle, and easy to handle.⁷²

3.1.4. Ovine model

The ovine model is the least common, with only one in vivo study identified.⁷³ Despite being similar to the human knee in terms of size, anatomy, vascularization, viscoelastic properties, cell density, and extracellular matrix collagen ultrastructure, it is characterized as softer, challenging to immobilize post-operatively, with an intra-articular FHL.^27,28,54

3.1.5. Canine model

Two canine models reported similar vascularization to the human meniscus.^74,75 However, canines exhibit a stronger intrinsic response to tissue damage, leading to fibrosis, and possess a smaller knee compared to humans and most other animals.^28,74 The extension and flexion angles (from 40° to 160°) in canines significantly differ from the human range of motion, and an intra-articular FHL is also found. Additionally, post-operative immobilization can be challenging.²⁹ Furthermore, dogs have a greater sagittal tibial than humans.⁷⁶

3.1.6. Rabbit model

The rabbit was the sole small animal model and also the most widely used for in vivo studies. They are inexpensive (around $40 for the animal itself, $10 for minor surgery, and $2 per diem), easily manageable, and it is possible to study several specimens at a time.⁷⁷ However, the rabbit's deep physiological flexion (exceeding 160°) results in significant biomechanical differences when compared to human knees. Additionally, rabbits are considerably smaller in size⁷⁸ and exhibit a significantly greater intrinsic healing capacity compared to humans or other large animals.⁷²

3.2. Analysis of study design and outcomes

The choice of animal model varied depending on the type of experiment. The ex vivo extra-articular study design (n = 41, 56.9%) was the most common, followed by the ex vivo intra-articular design (n = 20, 27.8%), and the in vivo study design (n = 11, 15.3%) (Fig. 3). Among all ex vivo experiments, only two animal models were used: porcine and bovine. Considering extra-articular studies, 63% were porcine models, and 37% were bovine models, while intra-articular studies had 86% porcine models, and 14% bovine models. In vivo experiments displayed the most diverse animal selection, with 36% of studies using rabbits, 29% using goats, 21% using dogs, and 7% each for sheep and pigs (Fig. 4). With regard to the type of meniscus tears performed, the majority of the studies induced longitudinal vertical tears (51.4%), followed by root tears (23%), radial tears (13.5%), bucket handle tears (10.8%), and horizontal tears (1.3%) (Fig. 5).

Fig. 3.

Experiment type distribution.

Fig. 4.

Ratio of each animal models for specific experiment type.

Fig. 5.

Induced tear distribution.

In terms of surgical techniques, 61 studies employed sutures (inside-out, outside-in, or all-inside), 15 used transosseous tunnel systems, 14 used arrows, and nine used other surgical devices such as anchors, staples, and screws (Fig. 6). The most commonly measured outcomes were biomechanical, including tensile strength (55.7%), gross or macroscopic observation (29.6%), histological (8.7%) and others (microangiography, arthrography, 3D micro-computed tomography (CT) analysis, electron microscopy) 6.1%.

Fig. 6.

Surgical technique and devices distribution.

The SYRCLE RoB tool for the critical appraisal of evidence and risk of bias in animal studies revealed substantial variations. All studies were classified as high risk of bias or unclear risk of bias.

4. Discussion

4.1. Animal models

The most significant finding of this systematic review is that porcine and bovine models are the only ones used and considered suitable for ex vivo studies. When it comes to in vivo studies, lapine and caprine models are the most common; however, the caprine and porcine models exhibit the characteristics closest to human menisci and should be prioritized. Additionally, a majority of studies were ex vivo, allowing relevant biomechanical analyses and lower costs for research teams. With the exception of canines, all ex vivo animal knees are theoretically available from the food industry, making them affordable and easy to acquire.^{26,30,32,34,36,37,44,47,48,50,52,}65, 66, 67^,69 Furthermore, ethics approval is not necessary when the animals come from the food industry,^26,44,45,79 although it remains essential when specimens come from another source or for in vivo studies. While the caprine model has yet to be used in ex vivo studies, it could be a suitable cadaveric model due to its anatomical similarity to the human knee. Storing ex vivo extra-articular specimens is straightforward, as they can all be frozen and do not require significant storage space in the laboratory.^30,32,34, 35, 36, 37^,45,47,49, 50, 51, 52^,65, 66, 67, 68, 69^,80,81 Additionally, ex vivo studies make it possible to analyze numerous menisci from young and healthy specimens of a comparable age, to explore the biomechanics of meniscal repair. This is challenging with human cadavers, which are generally older individuals with degenerative meniscal lesions or even without a meniscus and severe osteoarthritis.^39,48,79 Ex vivo animal studies are valuable to analyze the biomechanics and for proof of concept of new meniscal repair techniques, and can be used to test sutures, anchors, arrows, staples, screws, or other devices.¹¹ Conversely, in vivo studies offer a longitudinal examination of meniscal repairs over time and the biological reactions they induce.⁹ However, these studies incur higher costs than ex vivo studies and require the appropriate infrastructure. Depending on the study objective, considering an alternative study design or securing more funding might be necessary. The results from in vivo studies can reveal relevant biological data because they allow a follow-up of the knee's healing process after repairs.^70,71,73,82 It is crucial to recognize that ex vivo and in vivo studies are not in opposition to one another but rather part of a continuum, which is necessary and essential to the translation of surgical technology to humans.

Among the animals discussed in the present study, the porcine and caprine models were significantly closer to the human anatomy than the others. It should also be noted that although there are similarities in the general structure of human collagen and animal collagen, there are differences in proportion between the different types of collagen. Indeed, there are several types of collagen and the human meniscus is primarily composed of type I collagen, as opposed to animals. Nevertheless, this difference is inevitable when using animal models, and, once again, the porcine and caprine models are the most similar to the human meniscus in terms of collagen structure. Overall, there were major advantages and disadvantages for all the animals studied as reported in Table 1^11,29. The results from the SYRCLE tool reflect the low quality of all the studies included and the presence of an unclear or high risk of bias. There are also important differences in study design, as well as heterogeneity in animal type, tear type and outcomes measured that require careful interpretation of these results.

Table 1.

Summary of advantages and disadvantages for animal models used in meniscal repair research.

Animal model	Advantages	Disadvantages
Porcine	Availability (ex vivo), cost (ex vivo), similar size, anatomy (especially posterior root), vascularization, healing potential, cell density, collagen structures, cartilage thickness and weight, arthroscopy feasible.	Cost (in vivo), housing, aggressive, lack of full extension (40°), post-operative care, intra-articular flexor hallucis longus (FHL).
Bovine	Availability (ex vivo), cost (ex vivo), collagen structures.	Bigger size, resistance and thickness, lack of full extension, absence of in vivo study, intra-articular FHL.
Caprine	Anatomy, vascularization, viscoelastic properties, healing potential, cell density, collagen structures, gentle, arthroscopy feasible.	Absence of ex vivo study, post-operative immobilization and care, lack of full extension (40°), intra-articular FHL.
Ovine	Anatomy, vascularization, viscoelastic properties, healing potential, cell density, extracellular matrix structure.	Absence of ex vivo study, cost (in vivo), post-operative immobilization and care, softer. intra-articular FHL.
Canine	Vascularization, immobilization protocole feasible, arthroscopy feasible.	Public opinion, smaller, no ex vivo study, cost (in vivo), range of motion (40°–160°) stronger response to damages, intra-articular FHL.
Lapine	Availability (in vivo), cost, size for housing, number of specimens, gentle.	No ex vivo study, meniscal size and anatomy, arthroscopy not feasible, difficult surgery. intra-articular FHL.

Below are important considerations and recommendations for the various animal model.

4.1.1. Porcine

The porcine model is preferred for biomechanical testing, especially for studies on posterior root fixation considering that there is a similar transition zone between the body of the meniscus and the meniscal root.^17,47 The porcine model should, therefore, be considered for both ex vivo and in vivo studies, although costs may limit its use in the latter.

4.1.2. Bovine

There are no in vivo studies due to the space and infrastructure required considering that cows are too large for most laboratories. As bovine menisci are more resistant and thicker, devices designed for human meniscal repair can be unsuitable and may break, and this should be taken into account when choosing which devices to use. Nonetheless, the bovine meniscus is an appropriate substitute because of its biomechanical and histologic properties, especially for biomechanical ex vivo studies.

4.1.3. Caprine

The caprine model is interesting due to the anatomic similarities between human and goat menisci and the docility of these animals. However, post-operative immobilization and care can be challenging.^27,28 The caprine model should be favored for in vivo studies, and although not currently employed for ex vivo studies, it is also worthy of consideration for these.

4.1.4. Ovine

Although interesting in theory, the sheep model should not be the first choice due to the lack of literature on the subject.

4.1.5. Canine

Since dogs are common household pets in western society, public opinion can be critical of laboratory use for these animals which involves additional ethical considerations.^27,28 The anatomical structure and vascularization of their meniscus is close to the humans' and post-operative immobilization is relatively simple with dogs. However, the knee's biomechanics are affected by the elevated sagittal tibial slope and the canine model should not the first option.⁷⁶

4.1.6. Lapine

This is the most common animal model for in vivo study designs, most likely due to practical considerations such as the small size, lower cost, cheaper feeding requirement and availability of these animals.^83,84 However, it is severely lacking when considering anatomical and physiological similarities with the human knee, making it a suboptimal choice for pertinent and applicable clinical extrapolation.^18,29,78 Moreover, the small size of the knees makes them difficult to handle and not all procedures, namely arthroscopy, are feasible. The rabbit's rapid intrinsic healing capacity can also introduce biases in studies focusing on meniscal healing. Small animals are excellent for initial in vivo investigations and pilot studies, but the anatomical discrepancies with human knees limit their direct translation to human studies. The rabbit model highlights that animal models are frequently chosen for practical and economic reasons rather than anatomical and translational considerations. Finally, smaller animal models, such as rats and mice, do not have menisci large enough to perform meniscal repairs.

4.2. Tear type

This systematic review reveals that all types of meniscal tears, excluding ramp lesions, are studied and achievable. Vertical longitudinal tears are the most frequent in humans and also the most studied in animal models.⁸⁵ The porcine model is anatomically suitable to study root repairs; however, beyond that, there is no animal model to prioritize based on the type of tear to be studied.

4.3. Surgical techniques and devices

Sutures, whether inside-out, outside-in, or all-inside, are the most studied, but it is also possible to explore techniques involving transosseous tunnels or other devices such as anchors or arrows. It is essential to bear in mind that devices designed for humans may not necessarily be suitable for the size and strength of meniscal tissues in different animal models, and adjustments may be required based on the technique used. Some of the studies in this systematic review, focused on arthroscopic techniques in porcine, caprine, and canine models,⁷² which is something to consider in the translation to a clinical application. Note that all animal models presented here possess an intra-articular FHL, which can obstruct the view of the external meniscus during arthroscopy.

4.4. Outcomes

Biomechanical analyses are a crucial outcome in the assessment of meniscal repairs, but unfortunately, they are present in only a little more than half of the studies included (55.7%). Gross observation (29.6%) is often preferred over histological evaluation (8.7%), but it does not allow for microscopic analysis of the healing tissue. In ex vivo studies, biomechanical evaluation is the only relevant measurement, given that there is no possibility of healing, and should be systematic. For in vivo studies, it would be advisable to always complete histological analyses to assess meniscal tissue healing. Additionally, imaging techniques provide information on meniscal healing without the need to sacrifice the animal.

Currently, there is no consensus on the optimal animal model for meniscus-related research. Guidelines for meniscal research using animals are necessary to standardize the research approach and improve the reproducibility, comparability, translation, and validity of experiments. This systematic review provides crucial information for researchers undertaking an animal research project in meniscal repair.

5. Conclusions

This systematic review is a comprehensive guide for researchers involved in meniscal repair investigations, from ex vivo cadaveric studies, where porcine, caprine, and bovine models are preferred, to in vivo studies, which should prioritize porcine and caprine models due to their anatomical similarities with human structures. These two study designs are meant to complement one another, forming a continuum of research that addresses different questions to validate new techniques. Research teams should thoroughly understand the advantages and disadvantages of various animal models before initiating their protocols.

Ethical statement

Not applicable.

Funding statement

Marie-Lyne Nault: The institution (Hopital Sacré-Coeur de Montréal) has received departmental funding for research and educational purposes from: Arthrex, Conmed, Depuy, Linvatec, Smith & Nephew, Stryker, Synthes, Tornier, Wright, Zimmer Biomet. Departmental funding was also provided to CHU Sainte-Justine from Orthopaediatrics. This work was supported by Institut TransMedTech and its main financial partner, the Apogée Canada First Research Excellence Fund.

Guardian/patient's consent

Not applicable.

Data availability statement

Data available upon request.

CRediT authorship contribution statement

David Mazy: substantial contributions to the conception or design of the work, the acquisition, analysis, interpretation of data for the work, Writing – original draft, the work or revising it critically for important intellectual content. Daisy Lu: the acquisition, analysis, interpretation of data for the work, Writing – original draft, the work and revising it critically for important intellectual content. Sebastien Leclerc: the acquisition of data and critical revision for important intellectual content. Boaz Laor: the acquisition of data and critical revision for important intellectual content. Jessica Wang: data acquisition and critical revision for important intellectual content. Alix Pinvicy: substantial contributions to the conception or design of the work, the acquisition, analysis of data. Florina Moldovan: substantial contributions to the conception or design of the work, Writing – original draft, the work or revising it critically for important intellectual content. Marie-Lyne Nault: substantial contributions to the conception and design of the work, Writing – original draft, the work and revising it critically for important intellectual content, All authors gave final approval of the version to be published and agree to be accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.

Declaration of competing interest

Marie-Lyne Nault: The institution (Hopital Sacré-Coeur de Montréal) has received departmental funding for research and educational purposes from: Arthrex, Conmed, Depuy, Linvatec, Smith & Nephew, Stryker, Synthes, Tornier, Wright, Zimmer Biomet. Departmental funding was also provided to CHU Sainte-Justine from Orthopaediatrics. This work was supported by Institut TransMedTech and its main financial partner, the Apogée Canada First Research Excellence Fund.

The other authors declare no competing interests.

Appendix 1. Complete Search Strategy of the Five Databases

Table 1.1.

PubMed

1	Animal	Animals[MH:noexp] OR animals, laboratory[MH] OR Cattle[MH] OR Dogs[MH] OR Goats[MH] OR Sheep[MH] OR Rabbits[MH] OR swine[MH] OR Mole rat[MH] OR murinae[MH] OR models, animal[MH:noexp] OR species specificity[MH] OR animal*[TIAB] OR cattle*[TIAB] OR cow[TIAB] OR cows[TIAB] OR Dog[TIAB] OR Dogs[TIAB] OR canis[TIAB] OR goat*[TIAB] OR capra*[TIAB] OR sheep[TIAB] OR ovis[TIAB] OR rabbit*[TIAB] OR swine[TIAB] OR pig[TIAB] OR pigs[TIAB] OR mice*[TIAB] OR mouse*[TIAB] OR murine*[TIAB] OR rat[TIAB] OR rats[TIAB]
2	Meniscus	Meniscus[MH] OR “Tibial meniscus injuries"[MH] OR menisci[TIAB] OR meniscus[TIAB] OR semilunar cartilage*[TIAB] OR “semi-lunar cartilage*"[TIAB] OR flap tear*[TIAB] OR “bucket handle tear*"[TIAB] OR (menisc*[TIAB] AND (tear*[TIAB] OR horn[TIAB]))
3	Combinaison	1 and 2 3185 results obtained on 2022-07-15

Table 1.2.

Medline (OVID) MEDLINE(R) and Epub Ahead of Print, In-Process, In-Data-Review & Other Non-Indexed Citations and Daily 1946 to July 14, 2022

1	Animal	Animals/OR Exp animals, laboratory/OR Cattle/OR Dogs/OR Exp Goats/OR Exp Sheep/OR Rabbits/OR Exp swine/OR Exp Mole rat/OR Exp murinae/OR models, animal/OR species specificity/OR (animal* OR cattle* OR cow OR cows OR Dog OR Dogs OR canis OR goat* OR capra* OR sheep OR ovis OR rabbit* OR swine OR pig OR pigs OR mice* OR mouse* OR murine* OR rat OR rats).ti,ab,kw,kf
2	Meniscus	Exp Meniscus/OR “Tibial meniscus injuries"/OR (menisci OR meniscus OR semilunar cartilage* OR “semi-lunar cartilage*" OR flap tear* OR “bucket handle tear*" OR (menisc* AND (tear* OR horn))).ti,ab,kw,kf
3	Combinaison	1 and 2 Medline: 3185 results obtained on 2022-07-15

Table 1.3.

All EBM Reviews Cochrane Database of Systematic Reviews 2005 to July 13, 2022, EBM Reviews - ACP Journal Club 1991 to June 2022, EBM Reviews - Database of Abstracts of Reviews of Effects 1st Quarter 2016, EBM Reviews - Cochrane Clinical Answers June 2022, EBM Reviews - Cochrane Central Register of Controlled Trials June 2022, EBM Reviews - Cochrane Methodology Register 3rd Quarter 2012, EBM Reviews - Health Technology Assessment 4th Quarter 2016, EBM Reviews - NHS Economic Evaluation Database 1st Quarter 2016

1	Animal	Animals/OR Exp animals, laboratory/OR Cattle/OR Dogs/OR Exp Goats/OR Exp Sheep/OR Rabbits/OR Exp swine/OR Exp Mole rat/OR Exp murinae/OR models, animal/OR species specificity/OR (animal* OR cattle* OR cow OR cows OR Dog OR Dogs OR canis OR goat* OR capra* OR sheep OR ovis OR rabbit* OR swine OR pig OR pigs OR mice* OR mouse* OR murine* OR rat OR rats).ti,ab,kw,kf
2	Meniscus	Exp Meniscus/OR “Tibial meniscus injuries"/OR (menisci OR meniscus OR semilunar cartilage* OR “semi-lunar cartilage*" OR flap tear* OR “bucket handle tear*" OR (menisc* AND (tear* OR horn))).ti,ab,kw,kf
3	Combinaison	1 and 2 All EBM Reviews: 27 results obtained on 2022-07-15

Table 1.4.

Embase 1974 to 2022 July 14

1	Animal	Animal/OR Exp experimental animal/OR Exp bovine/OR Exp dog/OR Exp goat OR Exp sheep/OR exp Leporidae/OR Exp pig/OR Exp murine/OR Exp mole rat/OR animal model/OR species difference/OR (animal* OR cattle* OR cow OR cows OR Dog OR Dogs OR canis OR goat* OR capra* OR sheep OR ovis OR rabbit* OR swine OR pig OR pigs OR mice* OR mouse* OR murine* OR rat OR rats).ti,ab,kw
2	Meniscus	Exp Knee meniscus/OR “knee meniscus rupture"/OR (menisci OR meniscus OR semilunar cartilage* OR “semi-lunar cartilage*" OR flap tear* OR “bucket handle tear*" OR (menisc* AND (tear* OR horn))).ti,ab,kw,kf
3	Combinaison	1 and 2 Embase: 4602 results obtained on 2022-07-15

Table 1.5.

Web of Sciences

1	Animal	TS=(animal* OR cattle* OR cow OR cows OR Dog OR Dogs OR canis OR goat* OR capra* OR sheep OR ovis OR rabbit* OR swine OR pig OR pigs OR mice* OR mouse* OR murine* OR rat OR rats)
2	Meniscus	TS=(menisci OR meniscus OR semilunar cartilage* OR “semi-lunar cartilage*" OR flap tear* OR “bucket handle tear*" OR (menisc* AND (tear* OR horn)))
3	Combinaison	1 and 2 Web of Science: 9477 results obtained on 2022-07-15