Myra F. Barrett

Effect of Self-assembling Peptide, Chondrogenic Factors, and Bone Marrow Derived Stromal Cells on Osteochondral Repair

OBJECTIVE The goal of this study was to test the ability of an injectable self-assembling peptide (KLD) hydrogel with or without chondrogenic factors (CF) and allogeneic bone marrow stromal cells (BMSCs) to stimulate cartilage regeneration in a full-thickness, critically-sized, rabbit cartilage defect model in vivo. We used CF treatments to test the hypotheses that CF would stimulate chondrogenesis and matrix production by cells migrating into acellular KLD (KLD+CF) or by BMSCs delivered in KLD (KLD+CF+BMSCs). DESIGN Three groups were tested against contralateral untreated controls: KLD, KLD+CF, and KLD+CF+BMSCs, n=6-7. Transforming growth factor-β1 (TGF-β1), dexamethasone, and insulin-like growth factor-1 (IGF-1) were used as CF pre-mixed with KLD and BMSCs before injection. Evaluations included gross, histological, immunohistochemical and radiographic analyses. RESULTS KLD without CF or BMSCs showed the greatest repair after 12 weeks with significantly higher Safranin-O, collagen II immunostaining, and cumulative histology scores than untreated contralateral controls. KLD+CF resulted in significantly higher aggrecan immunostaining than untreated contralateral controls. Including allogeneic BMSCs+CF markedly reduced the quality of repair and increased osteophyte formation compared to KLD-alone. CONCLUSIONS These data show that KLD can fill full-thickness osteochondral defects in situ and improve cartilage repair as shown by Safranin-O, collagen II immunostaining, and cumulative histology. In this small animal model, the full-thickness critically-sized defect provided access to the marrow, similar in concept to abrasion arthroplasty or spongialization in large animal models, and suggests that combining KLD with these techniques may improve current practice.

Evaluation of articular cartilage progenitor cells for the repair of articular defects in an equine model

BACKGROUND We sought to determine the effectiveness of chondroprogenitor cells derived from autologous and allogenic articular cartilage for the repair of cartilage defects in an equine model. METHODS Cartilage defects (15 mm) were created on the medial trochlear ridge of the femur. The following experimental treatments were compared with empty-defect controls: fibrin only, autologous chondroprogenitor cells plus fibrin, and allogenic chondroprogenitor cells plus fibrin (n = 4 or 12 per treatment). Horses underwent strenuous exercise throughout the twelve-month study, and evaluations included lameness (pain) and arthroscopic, radiographic, gross, histologic, and immunohistochemical analyses. RESULTS Arthroscopy and microscopy indicated that defects in the autologous cell group had significantly better repair tissue compared with defects in the fibrin-only and control groups. Repair tissue quality in the allogenic cell group was not superior to that in the fibrin-only group with the exception of the percentage of type-II collagen, which was greater. Radiographic changes in the allogenic cell group were poorer on average than those in the autologous cell group. Autologous cells significantly reduced central osteophyte formation compared with fibrin alone. CONCLUSIONS On the basis of the arthroscopic, radiographic, and histologic scores, autologous cells in fibrin yielded better results than the other treatments; allogenic cells cannot be recommended at this time.

The arthroscopic and ultrasonographic boundaries of the equine femorotibial joints

REASONS FOR PERFORMING STUDY While descriptions of the visible soft tissues of the femorotibial joints exist for both arthroscopy and ultrasonography, there are few examples in the literature that discuss in detail the combined findings of these modalities. OBJECTIVES To further elucidate the ultrasonographic and arthroscopic boundaries of the normal equine femorotibial joints and improve the understanding of the benefits and limitations of each individual modality. METHODS Simultaneous arthroscopy and ultrasonography were performed in 10 equine cadaver stifles as well as bilateral stifles on a horse that underwent nonrecovery surgery. The arthroscopic probe was visualised ultrasonographically and concurrent video and still images acquired. RESULTS Arthroscopy provided good visualisation of the cranial meniscal ligaments, the distal portion of the cranial cruciate ligament, proximal portion of the medial collateral ligament within the fibrous tissue of the joint capsule and a limited view of the abaxial border of meniscus. Ultrasonography allowed for almost complete visualisation of the menisci, collateral ligaments and cranial meniscal ligaments and a portion of the cranial cruciate ligament. CONCLUSIONS By comparing the ultrasonographically and arthroscopically visible structures, this study allowed for a more complete understanding of the advantages and limitations of each modality. The ability of ultrasonography to resolve mild pathological changes should be further explored. POTENTIAL RELEVANCE When used together, these modalities can provide a more global image of the femorotibial joints.

Effects of the Combination of Microfracture and Self-Assembling Peptide Filling on the Repair of a Clinically Relevant Trochlear Defect in an Equine Model

BACKGROUND The goal of this study was to test the ability of an injectable self-assembling peptide (KLD) hydrogel, with or without microfracture, to augment articular cartilage defect repair in an equine cartilage defect model involving strenuous exercise. METHODS Defects 15 mm in diameter were created on the medial trochlear ridge and debrided down to the subchondral bone. Four treatment groups (n = 8 each) were tested: no treatment (empty defect), only defect filling with KLD, only microfracture, and microfracture followed by filling with KLD. Horses were given strenuous exercise throughout the one-year study. Evaluations included lameness, arthroscopy, radiography, and gross, histologic, immunohistochemical, biochemical, and biomechanical analyses. RESULTS Overall, KLD-only treatment of defects provided improvement in clinical symptoms and improved filling compared with no treatment, and KLD-only treatment protected against radiographic changes compared with microfracture treatment. Defect treatment with only microfracture also resulted in improved clinical symptoms compared with no treatment, and microfracture treatment resulted in repair tissue containing greater amounts of aggrecan and type-II collagen compared with KLD-only treatment. Microfracture treatment also protected against synovial fibrosis compared with no treatment and KLD-only treatment. Treatment with the self-assembling KLD peptide in combination with microfracture resulted in no additional improvements over microfracture-only treatment. In general, the nature of the predominant tissue in the defects was a mix of noncartilaginous and fibrocartilage tissue, with no significant differences among the treatments. CONCLUSIONS Treatment of defects with only KLD or with only microfracture resulted in an improvement in clinical symptoms compared with no treatment; the improvement likely resulted from different causes depending on the treatment. Whereas microfracture improved the quality of repair tissue, KLD improved the amount of filling and protected against radiographic changes. CLINICAL RELEVANCE Treatment of defects with only microfracture and with KLD only resulted in clinical improvements compared with untreated defects, despite differing with respect to the structural improvements that they induced.

Diagnostic stifle joint arthroscopy using a needle arthroscope in standing horses

OBJECTIVE To assess use of an 18 g arthroscope for diagnostic stifle joint examination in the standing horse. STUDY DESIGN Phase 1 used cadaver limbs and simultaneous ultrasonographic assessment. Phase 2 used 6 normal horses where stifles were assessed in both a standing and flexed position. Phase 3 used horses with suspected stifle injury or disease. ANIMALS Normal horses (n = 6) to assess ability to perform diagnostic procedure (phase 2) and 3 clinical cases (phase 3). METHODS Five cadaver limbs were used in phase 1 to assess all stifle joints. Phase 2 used standing sedated and locally anesthetized horses. Routine arthroscopic approaches were used in both weight bearing and flexed nonweight bearing positions. In both phase 1 and 2 simultaneous ultrasonographic and arthroscopic examinations were used to confirm extent of diagnostic examination. The methods developed in phase 2 were used to examine the stifle in 3 horses with suspected stifle disease. RESULTS In cadaveric limbs and horses, all intra articular structures that constitute a complete arthroscopic examination were identified; no intra -or postoperative morbidity occurred. In phase 3, the needle arthroscope was used in accurate identification of pathologic change and in 1 horse, an osteochondral fragment not detected by ultrasonography and radiography was identified. CONCLUSIONS This preliminary work indicates that an 18 g arthroscope can be used for diagnostic examination of the equine stifle in standing horses.

A comparison of arthroscopy to ultrasonography for identification of pathology of the equine stifle

REASONS FOR PERFORMING STUDY To evaluate and compare the diagnostic capability of arthroscopy and ultrasonography for the detection of pathological change in equine stifle joints. Although descriptions of the arthroscopic and ultrasonographic boundaries of the normal femorotibial joint exist, there are few examples in the literature comparing the pathological changes observed with each imaging modality. OBJECTIVES To evaluate and compare arthroscopic and ultrasonographic examinations for characterising pathological change in the stifle joint. To describe how the results of arthroscopic and ultrasonographic examinations may differ in characterising the severity of lesions and to evaluate which lesions are best assessed with each modality. STUDY DESIGN Retrospective review of ultrasonographic and arthroscopic examinations. METHODS The structures of the stifle joint were evaluated and graded for pathological change by scoring arthroscopic and ultrasonographic examinations. The presence and severity of the lesions were then compared between each modality. RESULTS Medial meniscal lesions were detected more often with ultrasonography than with arthroscopy. Conversely, arthroscopy was better for detection of cranial medial meniscotibial ligament (CrMMTL) tearing. Articular cartilage defects were best detected with arthroscopy and periarticular osteophytes of the medial femoral condyle with ultrasonography. Four cases had defects within one of the patellar ligaments, all of which were only characterised with ultrasonography. CONCLUSIONS Ultrasonography and arthroscopy should be combined to best evaluate pathology of the stifle, since each modality has its own limitations depending on the location and type of lesion.

An optimised injection technique for the navicular bursa that avoids the deep digital flexor tendon

REASONS FOR PERFORMING STUDY Injection of the navicular bursa is commonly performed from the palmar aspect of the limb, which results in penetration of the deep digital flexor tendon (DDFT). OBJECTIVES To report a radiographic guided injection from the lateral aspect of the limb that avoids puncture of the DDFT and to assess synovial and soft tissue penetration by the needle. STUDY DESIGN Prospective clinical and cadaveric study. METHODS Prospective analysis of cadaver limbs and clinical cases in which the navicular bursa was injected from the lateral aspect. Cadaver limbs were placed in a stand to simulate weight bearing and injection was performed in limbs without synovial distension or with distension of either the distal interphalangeal (DIP) joint, digital flexor tendon sheath (DFTS) or navicular bursa. In cadaver and clinical limbs, contrast was injected and the needle position assessed with radiographs. Cadaver (but not clinical) limbs were also examined using magnetic resonance imaging with the needle in situ. RESULTS Successful navicular bursal injection was achieved in all limbs (n = 71). Relative risk of DIP joint puncture was 19 times higher (95% confidence interval 1.3-285.4, P<0.001) when the DIP joint was distended (9 of 10 limbs) than in normal limbs (0 of 10 limbs). Relative risk of DFTS puncture was 2.7 times higher (95% confidence interval 1.0-7.2, P = 0.06) when the DFTS was distended (8 of 10 limbs) than in normal limbs (3 of 7 limbs). Synovial fluid was aspirated from 47% of bursae from clinical cases. CONCLUSIONS The lateral injection technique for the navicular bursa avoids penetration of the DDFT, although risk of synovial penetration must be considered when there is potential DIP joint or DFTS infection.

A review of how magnetic resonance imaging can aid in case management of common pathological conditions of the equine foot

Summary Magnetic resonance imaging (MRI) has become a valuable tool for the diagnosis of a multitude of conditions previously grouped into the vague diagnosis of palmar heel pain based on the response to palmar digital nerve diagnostic analgesia. The use of MRI not only determines a specific pathological diagnosis of the numerous structures within the foot but also the findings of the MRI help direct treatment and rehabilitation protocols, as well as providing prognostic information. Common injuries include damage to the navicular apparatus, deep digital flexor tendon, arthropathy of the distal interphalangeal joint and desmopathy of the collateral ligaments of the distal interphalangeal joint. This article reviews common MRI abnormalities in the equine foot and how treatment can be directed by the findings. Medical and surgical treatment options, as well as shoeing and rehabilitation protocols, are also discussed in relation to MRI findings. Using MRI can help create a more individually tailored and case-specific treatment regimen, which can, in turn, promote a more positive outcome in equine cases.

Use of contrast media in computed tomography and magnetic resonance imaging in horses: techniques, adverse events, and opportunities

The use of contrast media in computed tomography (CT) and magnetic resonance imaging (MRI) is increasing in horses. These contrast-enhanced imaging techniques provide improved tissue delineation and evaluation, thereby expanding diagnostic capabilities. While generally considered safe, not all contrast media exhibit the same safety profiles. The safety of contrast media use and descriptions of adverse events occurring in horses are sparsely reported. This review summarises the reported evidence of contrast media use and adverse events that occur in horses, with added contribution from other veterinary species and studies in man for comparison. This comprehensive data set empowers equine clinicians to develop use and monitoring strategies when working with contrast media. Finally, it summarises the current state-of-the-art and highlights the potential applications of contrast-enhanced CT and MRI for assessment of diseased or injured equine tissues, as well as (patho)physiological processes.

The role of MRI in selected equine case management.

Magnetic resonance imaging (MRI) allows for excellent evaluation of many types of soft tissue and osseous lesions. Using MRI as a diagnostic modality can help in developing an individualized treatment protocol. Case management can include both surgical and medical intervention. Various MRI findings and associated treatment protocols are described.