Biocompatibility of subcutaneously implanted marine macromolecules cross-linked bio-composite scaffold for cartilage tissue engineering applications

There is an intense interest in developing innovative biomaterials which support the invasion and proliferation of living cells for potential applications in tissue engineering and regenerative medicine. Present study demonstrated the in vivo biocompatibility and toxicity of a macromolecules cross-linked biocomposite scaffold composed of hydroxyapatite, alginate, chitosan and fucoidan abbreviated as HACF. The in vivo biocompatibility and toxicity of HACF scaffold were tested by comparing them with those of a biocompatible surgical metal implant (SMI) in a subcutaneous rat model. Following the implantation, animals were sacrificed and the scaffolds were resected at 1st, 4th, and 8th weeks; the surrounding tissue along with the implant was removed to evaluate its biocompatibility. The effects of implanted biomaterial scaffolds on vital organ systems such as liver, kidney, etc., have been studied by hematology and serum biochemistry. The activities of pro-inflammatory marker enzymes such as COX, 5-LOX, 15-LOX, and NOS were normal in rats implanted with HACF scaffold. Hematological parameters, antioxidant and lipid peroxidation status were also found to be normal in implanted rats same as that of control and SMI. The modulatory effect of implanted scaffold over inflammatory and stress signaling cascades were confirmed by the normalized mRNA expressions of NF-κB, TNF-α and IL-6. The histopathological analysis of liver, kidney and tissue support our results. Taken together, these results demonstrated that HACF biocomposite scaffold signifies its suitability for further research as a scaffold material for cartilage tissue engineering applications.     

Platelet‐rich plasma enhances the integration of bioengineered cartilage with native tissue in an in vitro model

Current therapies for cartilage repair can be limited by an inability of the repair tissue to integrate with host tissue. Thus, there is interest in developing approaches to enhance integration. We have previously shown that platelet‐rich plasma (PRP) improves cartilage tissue formation. This raised the question as to whether PRP could promote cartilage integration . Chondrocytes were isolated from cartilage harvested from bovine joints, seeded on a porous bone substitute and grown in vitro to form an osteochondral‐like implant. After 7 days, the biphasic construct was soaked in PRP for 30 min before implantation into the core of a donut‐shaped biphasic explant of native cartilage and bone. Controls were not soaked in PRP. The implant–explant construct was cultured for 2–4 weeks. PRP‐soaked bioengineered implants integrated with host tissue in 73% of samples, whereas controls only integrated in 19% of samples. The integration strength, as determined by a push‐out test, was significantly increased in the PRP‐soaked implant group (219 ± 35.4 kPa) compared with controls (72.0 ± 28.5 kPa). This correlated with an increase in glycosaminoglycan and collagen accumulation in the region of integration in the PRP‐treated implant group, compared with untreated controls. Immunohistochemical studies revealed that the integration zone contained collagen type II and aggrecan. The cells at the zone of integration in the PRP‐soaked group had a 3.5‐fold increase in matrix metalloproteinase‐13 gene expression compared with controls. These results suggest that PRP‐soaked bioengineered cartilage implants may be a better approach for cartilage repair due to enhanced integration.     

A Method to Cleave Target Molecules in a Neocartilage

The mechanical function of many matrix molecules is unknown. A common method to determine whether a molecule is a load-carrying structural molecule is to measure the mechanical properties of a tissue, digest the tissue with an enzyme specific for cleaving that molecule, and then remeasure the mechanical properties. A limitation of this technique is that there are no specific lytic enzymes for most molecules of interest. This article introduces a method that may allow evaluation of a large number of candidate structural molecules. A translated thrombin proteolytic recognition and cleavage site is inserted in the cDNA of a target molecule, and the target molecule then expressed in a cell that produces a tissue. After growing the tissue with cells expressing the engineered target molecule, the traditional procedure of mechanical testing, digesting, and retesting is performed. This method was demonstrated using decorin and its dermatan sulfate (DS) glycosaminoglycan chain in a neocartilage. A tissue was generated with cells expressing a genetically engineered decorin with a thrombin cleavage site. The tissue was then tested in tension and compression, digested with thrombin, and mechanically retested. The decorin protein was found in the tissue, the DS glycosaminoglycan chain was removed with thrombin digestion, and there was no change in the mechanical properties of the tissue due to the thrombin digestion relative to controls. These findings were in agreement with previously reported tests on decorin, collectively supporting the proposed method. All methods involving animals were reviewed and approved by our Institutional Review Board.     

Design-related risk factors for revision of primary cemented stems

Background and purpose Even small design variables of the femoral stem may influence the outcome of a hip arthroplasty. We investigated whether design-related factors play any role in the risk of non-aseptic revision of the 3 most frequently used primary cemented stem designs in the Swedish Hip Arthroplasty Register.

Patients and methods We studied 71,184 primary cemented femoral stem implants (21,008 Exeter polished stems, 43,036 Lubinus SPII stems, and 7,140 Spectron EF Primary stems) that were inserted from 1999 through 2006. Design-specific characteristics were analyzed using separate Cox regression models that were adjusted for sex, age, diagnosis, incision, and number of operations (first vs. second).

Results The crude revision rate varied between 0.8% (Lubinus SPII) and 1.4% (Spectron Primary). For the Exeter stem, the smallest femoral head diameter (22 mm) was associated with a higher risk of revision. No other design-specific parameters influenced the risk of revision of the Exeter stem. The smallest Lubinus stem size, a stem with extended neck length combined with a femoral head with increasing neck length, or the use of a cobalt-chromium head had a negative influence on the outcome. For the Spectron stem, the risk of revision was elevated for the smallest stem and for increasing offset calculated as the combined effect of high offset design and increasing neck length.

Interpretation Overall revision rates were low, but for two of the stems studied design factors such as size and neck length or offset influenced the risk of non-aseptic revision.