Sebastian Müller

Biologics for tendon repair

Tendon injuries are common and present a clinical challenge to orthopedic surgery mainly because these injuries often respond poorly to treatment and require prolonged rehabilitation. Therapeutic options used to repair ruptured tendons have consisted of suture, autografts, allografts, and synthetic prostheses. To date, none of these alternatives has provided a successful long-term solution, and often the restored tendons do not recover their complete strength and functionality. Unfortunately, our understanding of tendon biology lags far behind that of other musculoskeletal tissues, thus impeding the development of new treatment options for tendon conditions. Hence, in this review, after introducing the clinical significance of tendon diseases and the present understanding of tendon biology, we describe and critically assess the current strategies for enhancing tendon repair by biological means. These consist mainly of applying growth factors, stem cells, natural biomaterials and genes, alone or in combination, to the site of tendon damage. A deeper understanding of how tendon tissue and cells operate, combined with practical applications of modern molecular and cellular tools could provide the long awaited breakthrough in designing effective tendon-specific therapeutics and overall improvement of tendon disease management.

Repair of Focal Cartilage Defects With Scaffold-Assisted Autologous Chondrocyte Grafts Clinical and Biomechanical Results 48 Months After Transplantation

Background Scaffold-assisted autologous chondrocyte implantation is a clinically effective procedure for cartilage repair, but biomechanical evaluations are still missing. Purpose This study was conducted to assess the clinical efficacy, including biomechanical analyses, of BioSeed-C treatment for traumatic and degenerative cartilage defects of the knee. Study Design Case series; Level of evidence, 4. Methods The authors evaluated the midterm clinical and biomechanical outcome of BioSeed-C, a cell-based fibrin-polymer graft for the treatment of cartilage defects. Clinical outcome at 4-year follow-up was assessed in 52 patients with full-thickness cartilage defects, International Cartilage Repair Society (ICRS) stage III and IV. Clinical scoring was performed preoperatively and 48 months after implantation using the Lysholm score, the International Knee Documentation Committee (IKDC) score, the ICRS score, the Knee injury and Osteoarthritis Outcome Score (KOOS), and the Noyes score. Cartilage regeneration was assessed by magnetic resonance imaging (MRI) using the Henderson-Kreuz score. Biomechanical evaluation was performed by isokinetic strength measurements, comparing healthy and operated knee of each patient. Results Clinical evaluation showed significant improvement in the Lysholm (from 51.8 preoperatively to 80.7 at 48 months postoperatively), IKDC (from 47.5 to 71.5), ICRS (from 3.8 to 2.0), KOOS (subcategory pain from 62 to 78, symptoms from 68 to 76, activities of daily living from 68 to 85, sports from 19 to 55, and quality of life from 30 to 55), and Noyes (from 31 to 59) scores (P ≤ .001) 48 months after implantation of BioSeed-C compared with the preoperative situation. The MRI evaluations showed moderate to complete defect filling in 43 of 44 treated patients. Two patients without improvement in the clinical and MRI scores received a total knee endoprosthesis after 4 years. Isokinetic evaluation showed significantly reduced maximum strength capacities for knee flexion and extension at the operated knee compared with the healthy knee (P < .05). Conclusion The clinical outcomes 4 years after graft implantation are good despite a persisting strength deficit. Implanting Bio-Seed-C is a promising treatment option for cartilage defects of the knee. More emphasis should be put on the rehabilitation of muscular strength.

Influence of Sex on the Outcome of Autologous Chondrocyte Implantation in Chondral Defects of the Knee

Background: Sex-specific outcomes have been reported in anterior cruciate ligament reconstruction as well as in osteoarthrosis progression, but there are currently no related published data on autologous chondrocyte implantation (ACI). The present prospective study was performed to investigate sex-dependent differences in the results after ACI. Hypothesis: The clinical and magnetic resonance imaging (MRI) results after ACI of the knee are influenced by the patient’s sex. Study Design: Cohort study; Level of evidence, 2. Methods: The midterm clinical and MRI results of a cell-based fibrin-polymer graft for the treatment of full-thickness cartilage defects were evaluated preoperatively and 6, 12, and 48 months after surgery in 52 patients (male:female ratio, 25:27; average age, 35.6 years). Depending on the sex and the location of the defects (femoral condyles, n = 32; patellofemoral compartment, n = 20), patients were assigned to 4 different groups. Baseline clinical scores were compared with follow-up data by paired Wilcoxon tests for the Lysholm score and the International Knee Documentation Committee (IKDC) scoring system. Sex-specific differences were evaluated with the Mann-Whitney U test. The MRI evaluation was performed with the Henderson score at final follow-up. Results: Clinical scores improved in all groups over the whole study period (P < .05). Compared with female patients, male patients achieved significantly better results in the Lysholm score at all time intervals and in the IKDC score at 6 and 12 months after surgery (P < .05). In a subgroup analysis, female patients with patellar defects had the worst results in both clinical scores. With the available number of patients, MRI evaluation at 48 months after surgery revealed no significant difference in defect fill between male and female patients (P > .05). The Pearson correlation coefficient between both clinical scores and the MRI parameters of defect fill and cartilage signal was significant (P < .05). Conclusion: Autologous chondrocyte implantation is a promising treatment option for full-thickness cartilage defects of male and female knee joints. Female patients with patellar defects have worse prognostic factors.

Tendon healing: an overview of physiology, biology, and pathology of tendon healing and systematic review of state of the art in tendon bioengineering

PurposeTendon injuries vary from acute rupture to chronic tendinopathy. For an optimal treatment of either condition, a profound knowledge is essential. Therefore, this article shall give an overview of physiology, biology, and pathology of tendon healing and state of the art in tendon bioengineering.MethodsFor a preferably comprehensive survey, the current literature listed in PubMed and published in English peer-reviewed journals (March 2013) was systematically reviewed for tendon healing and tendon bioengineering including cytokine modulation, autologous sources of growth factors, biomaterials, gene therapy, and cell-based therapy. No differentiation was made between clinical and preclinical in vitro investigations.ResultsTendon healing happens in certain stadiums of inflammation, formation, and remodelling. An additional process of “collagen recycling” close to the healing site has been described recently. With increasing comprehension of physiology and pathology of tendon healing, several promising approaches in tendon bioengineering using growth factors, biomaterials, gene therapy, or cell-based therapy are described. However, only some of these are already used routinely in clinics.ConclusionStrong and resistant tendons are crucial for a healthy musculoskeletal system. The new approaches in tendon bioengineering are promising to aid physiological tendon healing and thus resulting in a stronger and more resistant tendon after injury. The growing knowledge in this field will need to be further taken into clinical studies so that especially those patients with prolonged courses, revision surgery, or chronic tendinopathy and high-demanding patients, i.e., professional athletes would benefit.Level of evidenceII.

All-Inside Meniscal Repair Devices Compared With Their Matched Inside-Out Vertical Mattress Suture Repair Introducing 10,000 and 100,000 Loading Cycles

Background: All-inside arthroscopic meniscal repairs are favored by most clinicians because of their lower complication rate and decreased morbidity compared with inside-out techniques. Until now, only 1000 cycles have been used for biomechanical testing. Hypothesis: All-inside meniscal repairs will show inferior biomechanical response to cyclic loading (up to 100,000 cycles) and load-to-failure testing compared with inside-out suture controls. Study Design: Controlled laboratory study. Methods: Bucket-handle tears in 72 porcine menisci were repaired using the Omnispan and Fast-Fix 360 (all-inside devices) and Orthocord 2-0 and Ultrabraid 2-0 sutures (matched controls). Initial displacement, displacement after cyclic loading (100, 500, 1000, 2000, 5000, 10,000, and 100,000 cycles) between 5 and 20 N, ultimate load to failure, and mode of failure were recorded, as well as stiffness. Results: Initial displacement and displacement after cyclic loading were not different between the groups. The Omnispan repair demonstrated the highest load-to-failure force (mean ± SD, 151.3 ± 21.5 N) and was significantly stronger than all the other constructs (Orthocord 2-0, 105.5 ± 20.4 N; Ultrabraid 2-0, 93.4 ± 22.5 N; Fast-Fix 360, 76.6 ± 14.2 N) (P < .0001 for all). The Orthocord vertical inside-out mattress repair was significantly stronger than the Fast-Fix 360 repair (P = .003). The Omnispan (30.8 ± 3.5 N/mm) showed significantly higher stiffness compared with the Ultrabraid 2-0 (22.9 ± 6.9 N/mm, P < .0001) and Fast-Fix 360 (23.7 ± 3.9 N/mm, P = .001). The predominant mode of failure was suture failure. Conclusion: All-inside meniscal devices show comparable biomechanical properties compared with inside-out suture repair in cyclic loading, even after 100,000 cycles. Clinical Relevance: Eight to 10 weeks of rehabilitation might not pose a problem for all repairs in this worst-case scenario.

Effect of a Simple Collagen Type I Sponge for Achilles Tendon Repair in a Rat Model

Background: Several sophisticated approaches to tendon engineering have been investigated as ways to improve tendon healing with the early formation of repair tissue with possibly a high amount of type I collagen. Besides the new formation of collagen type I, there is evidence for the natural integration of surrounding collagen type I from healthy tendon parts into the healing defect. However, the simple application of a type I collagen sponge to the healing site to increase the amount of local collagen type I has not been investigated. Hypothesis: Healing of the rat Achilles tendon can be accelerated by an additional supply of collagen type I, resulting in increased tear resistance. Study Design: Controlled laboratory study. Methods: The right Achilles tendons of 42 rats were transected. In half of the animals, a type I collagen sponge was placed into the gap. Animals were allowed to move freely in their cages to simulate early functional therapy. After 1, 2, and 4 weeks, tendon length, width, maximal load to failure, and stiffness were measured and the healing site studied histologically according to the Bonar score. Inflammation was evaluated by the appearance of macrophages and neutrophilic and eosinophilic granulocytes. Results: Defects receiving collagen sponges showed improved healing, with significantly stronger (29.5 vs 5.0 N, respectively, at 1 week; P = .00003), shorter (11.6 vs 14.5 mm, respectively, at 4 weeks; P = .005), thicker (10.0 vs 1.8 mm2, respectively, at 1 week; P = .00002), and less stiff (19.5 vs 30.5 N/mm, respectively, at 4 weeks; P = .02) tendons than control tendons. Overall, the biomechanical properties of the collagen-treated tendons appeared to be significantly closer to those of native, uninjured tendons compared with tendons in the control group. Histologically, no inflammatory reaction due to the collagen sponge was found. Conclusion: Tendon healing was accelerated by the type I collagen sponge. Moreover, the mechanical properties of collagen-treated tendons appeared to be significantly closer to those of normal, uninjured tendons compared with control tendons without collagen treatment. Clinical Relevance: As a simple type I collagen sponge seems to increase the amount of local collagen type I, the careful use of such sponges might be an option for tendon augmentation during Achilles tendon surgery.

The Role of the Paratenon in Achilles Tendon Healing: A Study in Rats

Background: The role of the paratenon in tendon healing is unknown. The present study compares healing in the presence or absence of the paratenon in an Achilles tendon defect model in rats. Hypothesis: Resection of the paratenon impairs tendon healing. Study Design: Controlled laboratory study. Methods: Sixty skeletally mature Sprague Dawley rats were randomly assigned to either a resected paratenon (RP) group or an intact paratenon (IP) group. In all animals, a 4-mm portion of the Achilles tendon was resected in the midsubstance. In the RP group, the paratenon was resected completely. In the IP group, the paratenon was opened longitudinally and closed again after the tendon defect had been created. One, 2, and 4 weeks after surgery, 7 animals per group were tested biomechanically and 3 animals per group examined histologically. Results: The recovery of mechanical strength was much more rapid in IP tendons. Tear resistance was significantly increased for IP tendons (41.3 ± 8.8 N and 47.3 ± 14.1 N, respectively) compared with RP tendons (19.3 ± 9.1 N and 33.2 ± 6.4 N, respectively) after 1 and 2 weeks. The cross-sectional area was larger in the IP group after 1 and 2 weeks (8.2 ± 2.3 mm2 and 11.3 ± 3.1 mm2 vs 5.0 ± 2.4 mm2 and 5.9 ± 2.0 mm2, respectively) compared with the RP group. Tendon stiffness was greater in the IP group after 1 week (10.4 ± 1.9 N/mm vs 4.5 ± 1.6 N/mm, respectively) compared with the RP group. In comparison, normal contralateral tendons had a maximal tear resistance of 56.6 ± 7.2 N, a cross-sectional area of 3.6 ± 0.7 mm2, and stiffness of 17.3 ± 3.8 N/mm. Hematoxylin and eosin staining revealed slightly delayed healing of RP tendons. Early collagen formation was seen in the IP group already after 1 week, whereas in the RP group, this only occurred after 2 weeks. After 4 weeks, the IP tendons showed more collagen crimp formation than the RP tendons. Conclusion: An intact paratenon promotes healing of the Achilles tendon. Clinical Relevance: Although incision or resection of the paratenon has been advocated when repairing injured or degenerative tendons, our data suggest that the integrity of the paratenon should be preserved.

Autograft versus sterilized allograft for lateral calcaneal lengthening osteotomies: Comparison of 50 patients.

AbstractSterilized allografts may be less resistant to collapse and prone to nonunion leading to loss of correction in open wedge osteotomies. These adverse events usually occur at early time points (i.e., < 9 months postoperatively). The goal of this study was to compare sterilized allografts to autologous grafts in respect to secondary loss of hindfoot alignment and graft incorporation after lateral calcaneal lengthening osteotomies.Fifty patients (22 F/ 28 M, age: 16–69 years) who had undergone 50 lateral calcaneal lengthening osteotomies for adult flatfoot deformity were included in this retrospective study. Cortical sterilized allografts were used in 25 patients, autologous grafts in the remaining 25. Patients’ preoperative, 6 and 12 weeks, and 6 to 9 months follow-up weight-bearing radiographs of the affected foot were analyzed by 2 blinded radiologists: on each radiograph, graft incorporation, the talo-first metatarsal angle (TFMA), the talo-navicular coverage angle (TNCA), and the calcaneal pitch angle (CPA) were assessed. Loss of hindfoot alignment was defined as an increase of the TFMA or the TNCA or a decrease of the CPA, each by 5°.Inter- and intraclass correlation coefficients for TFMA, TNCA, and CPA measurements ranged from 0.93 to 0.99. At all follow-up visits, the ratio of patients with loss of hindfoot alignment and graft incorporation was not significantly different between the allograft and autograft group. However, loss of correction was associated with failure of graft incorporation.Compared with autografts, sterilized allografts do not increase the risk for loss of hindfoot alignment in lateral column lengthening of the calcaneus. With respect to mechanical resistance, allografts thus mean an equal and valid alternative without risk of donor site morbidities.

Simulated activity but real trauma: a systematic review on nintendo wii injuries based on a case report of an acute anterior cruciate ligament rupture

AbstractVideo gaming injuries are classically regarded as eccentric accidents and novelty diagnoses. A case of an anterior cruciate ligament (ACL) tear sustained during Wii boxing spurned us to review the literature for other Wii-related injuries and Wii-based posttraumatic rehabilitation.The English literature listed in PubMed was systematically reviewed by searching for “Wii (trauma or injury or fracture).” Full-text articles were included after duplicate, blinded review. The type and treatment of injury as well as the Wii-based rehabilitation programs found were analyzed. Additionally, a new case of an acute ACL tear-sustained playing, Wii boxing, is additionally presented.After exclusion of irrelevant articles, 13 articles describing Wii-related injuries were included reporting on 3 fractures, 6 nonosseous, 2 overuse injuries, and 2 rehabilitation programs using Wii for posttraumatic rehabilitation. Among the presented Wii-related injuries, only 12.5% were treated conservatively, whereas 87.5% underwent either surgical or interventional treatment.Because of the reported case, the literature search was limited to Wii-related injuries excluding other video games. Another limitation of this article lies in the fact that mainly case reports but no controlled trials exist on the topic. Assumingly, primarily the more severe injuries are reported in the literature with an unknown number of possibly minor injuries.Motion-controlled video games, such as Wii, are becoming increasingly popular as a recreational entertainment. Because of their wide acceptance and entertaining nature, they are also increasingly recognized as a tool in rehabilitation. However, although the activity is simulated, injuries are real. Our systematic review shows that Wii gaming can lead to severe injuries, sometimes with lasting limitations.

Tendon Healing with Growth Factors

The incidence of sport injuries has increased in recent years due to fitness training and growing participation in sport activities by the general public. The tendon rupture was regarded as an injury typical of high-performance athletes. As physical and recreational activities become more and more popular followed by an increased frequency of soft tissue injuries, health care costs are raising. Tendon lacerations, ruptures, or inflammation cause marked morbidity and has a major impact on work, recreational activities, and daily needs. Tendon ruptures and tears are slow healing injuries that are often treated surgically with unsatisfactory results for some patients. As biology of healing processes and the influence of growth factors are becoming more and more clear, one can consider introducing biological therapy into clinical use. For optimizing treatment more understanding is needed. Therefore tendon physiology, pathology, ruptures biology and functionality, normal healing process, as well as the role of polypeptide factors during healing need to be known.