Shear stress induced by fluid flow produces improvements in tissue-engineered cartilage.

Tissue engineering aims to create implantable biomaterials for the repair and regeneration of damaged tissues. In vitro tissue engineering is generally based on static culture, which limits access to nutrients and lacks mechanical signaling. Using shear stress is controversial because in some cases it can lead to cell death while in others it promotes tissue regeneration. To understand how shear stress works and how it may be used to improve neotissue function, a series of studies were performed. First, a tunable device was designed to determine optimal levels of shear stress for neotissue formation. Then, computational fluid dynamics modeling showed the device applies fluid-induced shear (FIS) stress spanning three orders of magnitude on tissue-engineered cartilage (neocartilage). A beneficial window of FIS stress was subsequently identified, resulting in up to 3.6-fold improvements in mechanical properties of neocartilage in vitro. In vivo, neocartilage matured as evidenced by the doubling of collagen content toward native values. Translation of FIS stress to human derived neocartilage was then demonstrated, yielding analogous improvements in mechanical properties, such as 168% increase in tensile modulus. To gain an understanding of the beneficial roles of FIS stress, a mechanistic study was performed revealing a mechanically gated complex on the primary cilia of chondrocytes that is activated by FIS stress. This series of studies places FIS stress into the arena as a meaningful mechanical stimulation strategy for creating robust and translatable neotissues, and demonstrates the ease of incorporating FIS stress in tissue culture.

Tendon and ligament as novel cell sources for engineering the knee meniscus.

OBJECTIVE: The application of cell-based therapies in regenerative medicine is hindered by the difficulty of acquiring adequate numbers of competent cells. For the knee meniscus in particular, this may be solved by harvesting tissue from neighboring tendons and ligaments. In this study, we have investigated the potential of cells from tendon and ligament, as compared to meniscus cells, to engineer scaffold-free self-assembling fibrocartilage. METHOD: Self-assembling meniscus-shaped constructs engineered from a co-culture of articular chondrocytes and either meniscus, tendon, or ligament cells were cultured for 4 weeks with TGF-ß1 in serum-free media. After culture, constructs were assessed for their mechanical properties, histological staining, gross appearance, and biochemical composition including cross-link content. Correlations were performed to evaluate relationships between biochemical content and mechanical properties. RESULTS: In terms of mechanical properties as well as biochemical content, constructs engineered using tenocytes and ligament fibrocytes were found to be equivalent or superior to constructs engineered using meniscus cells. Furthermore, cross-link content was found to be correlated with engineered tissue tensile properties. CONCLUSION: Tenocytes and ligament fibrocytes represent viable cell sources for engineering meniscus fibrocartilage using the self-assembling process. Due to greater cross-link content, fibrocartilage engineered with tenocytes and ligament fibrocytes may maintain greater tensile properties than fibrocartilage engineered with meniscus cells.

Bracing can partially limit tibial rotation during stressful activities after anterior crucial ligament reconstruction with a hamstring graft.

BACKGROUND: Hamstring graft has substantial differences with BPTB graft regarding initial mechanical strength, healing sequence, and vascularization, which may imply that a different approach during rehabilitation period is required. The purpose of this study was to investigate the influence of knee bracing on tibial rotation in ACL-reconstructed patients with a hamstring autograft during high loading activities. The hypothesis was that there would be a decrease in tibial rotation in the ACL-reconstructed braced knee as compared to the unbraced knee. METHODS: Twenty male patients having undergone unilateral ACL reconstruction with a semitendinosus/gracilis autograft were assessed. Kinematic data were collected with an eight-camera optoelectronic system during two stressful tasks: (1) descending from a stair and subsequent pivoting; and (2) landing from a platform and subsequent pivoting. In each patient, three different experimental conditions were evaluated: (A) wearing a prophylactic brace (braced condition); (B) wearing a patellofemoral brace (sleeved condition); (C) without brace (unbraced condition). The intact knee without brace served as a control. RESULTS: Tibial rotation was significantly lower in the intact knee compared to all three conditions of the ACL-reconstructed knee (P≤0.01 for both tasks). Presence of a brace or sleeve resulted in lower tibial rotation than in the unbraced condition (p=0.003 for descending/pivot and P=0.0004 for landing/pivot). The braced condition resulted in lower rotation than the sleeved condition for descending/pivoting (P=0.031) while no differences were found for landing/pivoting (P=0.230). CONCLUSION: Knee bracing limited the excessive tibial rotation during pivoting under high loading activities in ACL-reconstructed knees with a hamstring graft. This partial restoration of normal kinematics may have a potential beneficial effect in patients recovering from ACL reconstruction with a hamstring autograft. LEVEL OF EVIDENCE: Level III, case-control therapeutic study.

Multiple recurrences and late metastasis of adamantinoma in the tibia: a case report.

Adamantinoma is a rare, low-grade, malignant bone tumour. We report on a 46-year-old woman who had early multiple recurrences of adamantinoma of the right tibia and late metastasis to the lung and ribs 13 years after the first surgical treatment. She underwent multiple complete tumour excisions and eventually below-knee amputation and removal of the left lung and sixth to eighth ribs.

Rupture of anterior cruciate ligament monitored by acoustic emission.

The scope of this study is to relate the acoustic emission (AE) during rupture of human soft tissue (anterior cruciate ligament, ACL) to the mechanisms leading to its failure. The cumulative AE activity highlights the onset of serious damage, while other parameters, show repeatable tendencies, being well correlated with the tissue's mechanical behavior. The frequency content of AE signals increases throughout the experiment, while other indices characterize between different modes of failure. Results of this preliminary study show that AE can shed light into the failure process of this tissue, and provide useful data on the ACL reconstruction.

ACL injury and reconstruction: Clinical related in vivo biomechanics.

Several researchers including our group have shown that knee joint biomechanics are impaired after anterior cruciate ligament (ACL) injury, in terms of kinematics and neuromuscular control. Current ACL reconstruction techniques do not seem to fully restore these adaptations. Our research has demonstrated that after ACL reconstruction, excessive tibial rotation is still present in high-demanding activities that involve both anterior and rotational loading of the knee. These findings seem to persist regardless of the autograft selection for the ACL reconstruction. Our results also suggest an impairment of neuromuscular control after ACL reconstruction, although muscle strength may have been reinstated. These abnormal biomechanical patterns may lead to loading of cartilage areas, which are not commonly loaded in the healthy knee and longitudinally can lead to osteoarthritis. Muscle imbalance can also influence patients' optimal sports performance exposing them to increased possibility of knee re-injury. In this review, our recommendations point towards further experimental work with in vivo and in vitro studies, in order to assist in the development of new surgical procedures that could possibly replicate more closely the natural ACL anatomy and prevent future knee pathology.

The role of radiation dose in a combined therapeutic protocol for the prevention of heterotopic ossification after total hip replacement.

PURPOSE: To present the results of a prospective study which aimed to evaluate the efficacy of radiation dose in a combined protocol using postoperative radiotherapy (RT) and indomethacin for the prevention of heterotopic ossification (HO) in patients undergoing total hip arthroplasty (THA) and are at high risk for HO development. METHODS: Seventy-one patients with a mean age of 63 years received either a single dose of 7 Gy or a fractionated dose of 10 Gy in 5 fractions of 2 Gy within the 3 postoperative days. Concurrently all patients received 75 mg of indomethacin for 15 days. Patients were analysed for radiographical evidence of HO development and clinically with the Merle d'Aubigné score at 1 year. RESULTS: At 12 months combined RT and indomethacin achieved excellent prophylaxis of HO. The overall radiographical incidence of HO was 7.04% (95% CI 2.33-15.67), while no patient with clinically significant HO (Brooker III-IV) was seen. There was no statistically significant difference between the two RT protocols. In a subgroup of 12 patients with bilateral THA the incidence of HO in the non-irradiated hips was statistically significantly higher compared with the irradiated hips. All patients had improved joint mobility and function during follow up compared with the preoperative period. No statistically significant differences regarding the Merle d'Aubigné score was documented between the 2 RT groups. No acute or late side effects related to RT were noted. CONCLUSION: This study demonstrated the efficacy of combined RT and indomethacin in preventing heterotopic ossification after total hip arthroplasty. Fractionated total dose of 10 Gy seems to offer no further benefit compared to a single dose of 7.0 Gy.

Functional outcome after excision of heterotopic ossification about the knee in ICU patients.

The objective of this study was to evaluate the degree of improvement in the range of movement in the knee joint, sitting ability, and overall ambulation in patients with heterotopic ossification of the knee joint who underwent surgical excision of ectopic bone. Between 1999 and 2006, 14 patients (23 joints) with significant heterotopic ossification of the knee joint that required surgery were evaluated. We compared the range of movement in the knee joint, sitting ability, and overall ambulation in the preoperative and postoperative periods using the Fuller and Keenan classification systems. Range of movement increased in 82% of cases (19 knee joints). Sitting ability improved in 13 patients (93%). Postoperatively, ambulation in eight patients (57%) was remarkably superior. In conclusion, resection of heterotopic ossification may significantly improve the range of movement in the knee joint, sitting ability, and overall ambulation.