Biocompatibility and degradation comparisons of four biodegradable copolymeric osteosynthesis systems used in maxillofacial surgery: A goat model with four years follow-up.

Applying biodegradable osteosyntheses avoids the disadvantages of titanium osteosyntheses. However, foreign-body reactions remain a major concern and evidence of complete resorption is lacking. This study compared the physico-chemical properties, histological response and radiographs of four copolymeric biodegradable osteosynthesis systems in a goat model with 48-months follow-up. The systems were implanted subperiosteally in both tibia and radius of 12 Dutch White goats. The BioSorb FX [poly(70LLA-co-30DLLA)], Inion CPS [poly([70-78.5]LLA-co-[16-24]DLLA-co-4TMC)], SonicWeld Rx [poly(DLLA)], LactoSorb [poly(82LLA-co-18GA)] systems and a negative control were randomly implanted in each extremity. Samples were assessed at 6-, 12-, 18-, 24-, 36-, and 48-month follow-up. Surface topography was performed using scanning electron microscopy (SEM). Differential scanning calorimetry and gel permeation chromatography were performed on initial and explanted samples. Histological sections were systematically assessed by two blinded researchers using (polarized) light microscopy, SEM and energy-dispersive X-ray analysis. The SonicWeld Rx system was amorphous while the others were semi-crystalline. Foreign-body reactions were not observed during the complete follow-up. The SonicWeld Rx and LactoSorb systems reached bone percentages of negative controls after 18 months while the BioSorb Fx and Inion CPS systems reached these levels after 36 months. The SonicWeld Rx system showed the most predictable degradation profile. All the biodegradable systems were safe to use and well-tolerated (i.e., complete implant replacement by bone, no clinical or histological foreign body reactions, no [sterile] abscess formation, no re-interventions needed), but nanoscale residual polymeric fragments were observed at every system's assessment.

Meniscus surgery is still widely performed in the treatment of degenerative meniscus tears in The Netherlands.

PURPOSE: Studies have demonstrated rising incidences of meniscus procedures for degenerative meniscus tears in several countries, despite accumulating evidence that questions the efficacy of the treatment. It is not clear if this rise in incidences also applies to the practice of arthroscopic surgery in the Netherlands. The objective of this study was, therefore, to evaluate the number of meniscal surgeries performed in the Netherlands between 2005 and 2014. METHODS: We used registry-based data on meniscal surgeries that originated from Dutch national hospital basic care registrations from 2005 to 2014. Poisson regression models were used to test differences in incidences of meniscus surgeries performed in the Netherlands between 2005 and 2014, and to find out if changes in incidences over this period differed for younger and older patients. RESULTS: The number of meniscus surgeries was highest in patients aged 40-65 years, who accounted for half of the total number of meniscal surgeries. The incidences of meniscus surgeries decreased from 2005 to 2014 (p < 0.001); this decrease was observed in all age groups, although the decrease in incidences was more pronounced for younger patients (aged less than 40 years) compared to middle-aged and older patients (aged 40 years and older) (p < 0.001). CONCLUSIONS: The implementation of a nationwide guideline for arthroscopic procedures for meniscus tears may have contributed to a decrease in incidences of meniscus procedures. Despite accumulating evidence that questions the rationalisation and effectiveness of the treatment, meniscus surgery is still widely performed in the treatment of degenerative meniscus tears in the Netherlands, demonstrating a delay in the dissemination, acceptance, and implementation of clinical evidence in the practice of arthroscopic surgery in the Netherlands. LEVEL OF EVIDENCE: II.

Augmented cartilage regeneration by implantation of cellular versus acellular implants after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

Bone marrow stimulation may be applied to regenerate focal cartilage defects, but generally results in transient clinical improvement and formation of fibrocartilage rather than hyaline cartilage. Tissue engineering and regenerative medicine strive to develop new solutions to regenerate hyaline cartilage tissue. This systematic review and meta-analysis provides a comprehensive overview of current literature and assesses the efficacy of articular cartilage regeneration by implantation of cell-laden versus cell-free biomaterials in the knee and ankle joint in animals after bone marrow stimulation. PubMed and EMBASE (via OvidSP) were systematically searched using tissue engineering, cartilage and animals search strategies. Included were primary studies in which cellular and acellular biomaterials were implanted after applying bone marrow stimulation in the knee or ankle joint in healthy animals. Study characteristics were tabulated and outcome data were collected for meta-analysis for studies applying semi-quantitative histology as outcome measure (117 studies). Cartilage regeneration was expressed on an absolute 0-100% scale and random effects meta-analyses were performed. Implantation of cellular biomaterials significantly improved cartilage regeneration by 18.6% compared to acellular biomaterials. No significant differences were found between biomaterials loaded with stem cells and those loaded with somatic cells. Culture conditions of cells did not affect cartilage regeneration. Cartilage formation was reduced with adipose-derived stem cells compared to other cell types, but still improved compared to acellular scaffolds. Assessment of the risk of bias was impaired due to incomplete reporting for most studies. Implantation of cellular biomaterials improves cartilage regeneration compared to acellular biomaterials.

In Vitro and In Vivo Characterization of Biodegradable Reactive Isocyanate-Terminated Three-Armed- and Hyperbranched Block Copolymeric Tissue Adhesives.

Tissue adhesives are an attractive class of biomaterials, which can serve as a treatment for meniscus tears. In this study, physicochemical and adhesive properties of novel biodegradable three-armed- and hyperbranched block copolymeric adhesives are evaluated. Additionally, their degradation in vitro and in vivo, and the tissue reaction after subcutaneous injection in rats are assessed. The developed adhesives have sufficient adhesive strength to meniscus tissue after curing (66-88 kPa). Networks based on the three-armed adhesive have tensile properties that are in the same range as human meniscus. After 26 weeks, networks based on the hyperbranched adhesive show a faster mass loss (25.4%) compared to networks prepared from the three-armed ones (5.5%). Both adhesives induce an inflammatory reaction, however, no necrosis and only initial toxic effects on peripheral tissues are observed. The proposed materials are suitable candidates for the use as resorbable tissue adhesives for meniscus repair.

In Vivo Performance of a Novel, Anatomically Shaped, Total Meniscal Prosthesis Made of Polycarbonate Urethane: A 12-Month Evaluation in Goats.

BACKGROUND: Injury or loss of the meniscus generally leads to degenerative osteoarthritic changes in the knee joint. However, the treatment options for symptomatic patients with total meniscectomy are limited. Therefore, we developed a novel, anatomically shaped, total meniscal implant made of polycarbonate urethane. PURPOSE: To evaluate the in vivo performance of this novel total meniscal implant. The assessment particularly focused on the implant's response to long-term physiological loading in a goat model and its chondroprotective capacity in comparison to clinically relevant controls. STUDY DESIGN: Controlled laboratory study. METHODS: Surgery was performed to the stifle joint of 26 female Saanen goats, subdivided into 4 groups: implant, allograft, total meniscectomy, and sham surgery. The sham group's contralateral joints served as nonoperated controls. After 12 months of follow-up, investigators evaluated implant wear, deformation, and the histopathological condition of the synovium and cartilage. RESULTS: Wear of the implant's articulating surfaces was minimal, which was confirmed by the absence of wear particles in the synovial fluid. Implant deformation was limited. However, one implant failed by complete tearing of the posterior horn extension. No differences in cartilage histopathological condition were observed for the implant, allograft, and meniscectomy groups. However, locally, the cartilage scores for these groups were significantly worse than those of the nonoperated controls. CONCLUSION: Whereas this study demonstrated that the novel implant is resistant to wear and that deformation after 12 months of physiological loading is acceptable, reinforcement of the implant horns is necessary to prevent horn failure. Although the implant could not protect the cartilage from developing degenerative changes, the progression of damage was similar in the allograft group. CLINICAL RELEVANCE: This novel polycarbonate urethane implant may have the potential to become an alternative treatment for symptomatic patients with total meniscectomy.

Development of a fast curing tissue adhesive for meniscus tear repair.

Isocyanate-terminated adhesive amphiphilic block copolymers are attractive materials to treat meniscus tears due to their tuneable mechanical properties and good adhesive characteristics. However, a drawback of this class of materials is their relatively long curing time. In this study, we evaluate the use of an amine cross-linker and addition of catalysts as two strategies to accelerate the curing rates of a recently developed biodegradable reactive isocyanate-terminated hyper-branched adhesive block copolymer prepared from polyethylene glycol (PEG), trimethylene carbonate, citric acid and hexamethylene diisocyanate. The curing kinetics of the hyper-branched adhesive alone and in combination with different concentrations of spermidine solutions, and after addition of 2,2-dimorpholinodiethylether (DMDEE) or 1,4-diazabicyclo [2.2.2] octane (DABCO) were determined using FTIR. Additionally, lap-shear adhesion tests using all compositions at various time points were performed. The two most promising compositions of the fast curing adhesives were evaluated in a meniscus bucket handle lesion model and their performance was compared with that of fibrin glue. The results showed that addition of both spermidine and catalysts to the adhesive copolymer can accelerate the curing rate and that firm adhesion can already be achieved after 2 h. The adhesive strength to meniscus tissue of 3.2-3.7 N was considerably higher for the newly developed compositions than for fibrin glue (0.3 N). The proposed combination of an adhesive component and a cross-linking component or catalyst is a promising way to accelerate curing rates of isocyanate-terminated tissue adhesives.

The effect of tissue surface modification with collagenase and addition of TGF-ß3 on the healing potential of meniscal tears repaired with tissue glues in vitro.

The aim of the current in vitro study was to investigate if tissue surface modification with collagenase and addition of the TGF-ß3 can increase the number of cells present in meniscus tears repaired with the use of newly developed tissue adhesives based on isocyanate-terminated block copolymers. Cylindrical explants were harvested from the inner part of bovine menisci. To simulate a full-thickness tear, the central core of the explants was removed and glued back into the defect, with or without incubation in collagenase solution prior to gluing. The repair constructs were then cultured with or without addition of TGF-ß3, and assessed for their histological appearance. The histological staining of the constructs confirmed that both developed adhesives were not cytotoxic. After 28 days, meniscus cells were present in direct contact with the glues. The addition of TGF-ß3 to the culture medium resulted in the presence of cells that formed a sheath inside the simulated tear and in increased cell numbers at the edges of annulus of the explants. In the group in which the tissue was incubated in collagenase and cultured in medium containing TGF-ß3, thicker layers of cells were observed. These results suggest that repairing the torn meniscus with tissue adhesives after pre-treatment of the tissue with collagenase and stimulation with TGF-ß3 is a very promising treatment method, especially when treating the inner avascular part of the meniscus. Nevertheless, longer-term in vitro and in vivo studies are needed to confirm the beneficial effects of this combination therapy.

Preparation of Designed Poly(trimethylene carbonate) Meniscus Implants by Stereolithography: Challenges in Stereolithography.

Three-armed poly(trimethylene carbonate) macromers with a relatively high molecular weight of 28.9 kg mol-1 are prepared by ring opening polymerization and subsequent functionalization with methacrylate end groups. A resin suitable for processing by stereolithography is developed using propylene carbonate as a diluent, a photoinitiator, and a dye to control the curing characteristics. The difficulties in building designed structures with digital light processing stereolithography and the ways of optimizing the resin compositions are described in detail. Using an optimized resin composition, which contained 50 wt% macromer, 50 wt% diluent, 0.05 wt% (relative to the macromer) dye, and 5 wt% (relative to the macromer) photoinitiator, designed 3D porous structures with a gyroid pore network geometry are manufactured. By varying pore sizes and porosities between, respectively, 300 and 1000 µm and 60% and 90%, cylindrical porous poly(trimethylene carbonate) network structures with compression moduli of 85-2320 kPa are prepared. A porous poly(trimethylene carbonate) network meniscus implant is designed on the basis of computed tomography imaging data. By adjusting the characteristics of the gyroid pore architecture, an implant with a compression modulus close to 400 kPa, which fits the compression modulus of human meniscal tissue, is manufactured by stereolithography.

Improved cartilage regeneration by implantation of acellular biomaterials after bone marrow stimulation: a systematic review and meta-analysis of animal studies.

Microfracture surgery may be applied to treat cartilage defects. During the procedure the subchondral bone is penetrated, allowing bone marrow-derived mesenchymal stem cells to migrate towards the defect site and form new cartilage tissue. Microfracture surgery generally results in the formation of mechanically inferior fibrocartilage. As a result, this technique offers only temporary clinical improvement. Tissue engineering and regenerative medicine may improve the outcome of microfracture surgery. Filling the subchondral defect with a biomaterial may provide a template for the formation of new hyaline cartilage tissue. In this study, a systematic review and meta-analysis were performed to assess the current evidence for the efficacy of cartilage regeneration in preclinical models using acellular biomaterials implanted after marrow stimulating techniques (microfracturing and subchondral drilling) compared to the natural healing response of defects. The review aims to provide new insights into the most effective biomaterials, to provide an overview of currently existing knowledge, and to identify potential lacunae in current studies to direct future research. A comprehensive search was systematically performed in PubMed and EMBASE (via OvidSP) using search terms related to tissue engineering, cartilage and animals. Primary studies in which acellular biomaterials were implanted in osteochondral defects in the knee or ankle joint in healthy animals were included and study characteristics tabulated (283 studies out of 6,688 studies found). For studies comparing non-treated empty defects to defects containing implanted biomaterials and using semi-quantitative histology as outcome measure, the risk of bias (135 studies) was assessed and outcome data were collected for meta-analysis (151 studies). Random-effects meta-analyses were performed, using cartilage regeneration as outcome measure on an absolute 0-100% scale. Implantation of acellular biomaterials significantly improved cartilage regeneration by 15.6% compared to non-treated empty defect controls. The addition of biologics to biomaterials significantly improved cartilage regeneration by 7.6% compared to control biomaterials. No significant differences were found between biomaterials from natural or synthetic origin or between scaffolds, hydrogels and blends. No noticeable differences were found in outcome between animal models. The risk of bias assessment indicated poor reporting for the majority of studies, impeding an assessment of the actual risk of bias. In conclusion, implantation of biomaterials in osteochondral defects improves cartilage regeneration compared to natural healing, which is further improved by the incorporation of biologics.

Degradation behavior of, and tissue response to photo-crosslinked poly(trimethylene carbonate) networks.

Photo-crosslinked networks prepared from three-armed methacrylate functionalized PTMC oligomers (PTMC-tMA macromers) are attractive materials for developing an anatomically correct meniscus scaffold. In this study, we evaluated cell specific biocompatibility, in vitro and in vivo degradation behavior of, and tissue response to, such PTMC networks. By evaluating PTMC networks prepared from PTMC-tMA macromers of different molecular weights, we were able to assess the effect of macromer molecular weight on the degradation rate of the PTMC network obtained after photo-crosslinking. Three photo-crosslinked networks with different crosslinking densities were prepared using PTMC-tMA macromers with molecular weights 13.3, 17.8, and 26.7 kg/mol. Good cell biocompatibility was demonstrated in a proliferation assay with synovium derived cells. PTMC networks degraded slowly, but statistically significant, both in vitro as well as subcutaneously in rats. Networks prepared from macromers with higher molecular weights demonstrated increased degradation rates compared to networks prepared from initial macromers of lowest molecular weight. The degradation process took place via surface erosion. The PTMC networks showed good tissue tolerance during subcutaneous implantation, to which the tissue response was characterized by the presence of fibrous tissue and encapsulation of the implants. Concluding, we developed cell and tissue biocompatible, photo-crosslinked PTMC networks using PTMC-tMA macromers with relatively high molecular weights. These photo-crosslinked PTMC networks slowly degrade by a surface erosion process. Increasing the crosslinking density of these networks decreases the rate of surface degradation. © 2016 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 104A: 2823-2832, 2016.

Inflammatory conditions partly impair the mechanically mediated activation of Smad2/3 signaling in articular cartilage.

BACKGROUND: Joint trauma, which is frequently related with mechanical overloading of articular cartilage, is a well-established risk for osteoarthritis (OA) development. Additionally, reports show that trauma leads to synovial joint inflammation. In consequence, after joint trauma, cartilage is influenced by deleterious excessive loading combined with the catabolic activity of proinflammatory mediators. Since the activation of TGF-ß signaling by loading is considered to be a key regulatory pathway for maintaining cartilage homeostasis, we tested the effect of proinflammatory conditions on mechanically mediated activation of TGF-ß/Smad2/3P signaling in cartilage. METHODS: Cartilage explants were subjected to dynamic mechanical compression in the presence of interleukin-1 beta (IL-1ß) or osteoarthritic synovium-conditioned medium (OAS-CM). Subsequently, the activation of the Smad2/3P pathway was monitored with QPCR analysis of reporter genes and additionally the expression of receptors activating the Smad2/3P pathway was analyzed. Finally, the ability for mechanically mediated activation of Smad2/3P was tested in human OA cartilage. RESULTS: IL-1ß presence during compression did not impair the upregulation of Smad2/3P reporter genes, however the results were affected by IL-1ß-mediated upregulations in unloaded controls. OAS-CM significantly impaired the compression-mediated upregulation of bSmad7 and Tgbfb1. IL-1ß suppressed the compression-mediated bAlk5 upregulation where 12 MPa compression applied in the presence of OAS-CM downregulated the bTgfbr2. Mechanically driven upregulation of Smad2/3P reporter genes was present in OA cartilage. CONCLUSIONS: Proinflammatory conditions partly impair the mechanically mediated activation of the protective TGF-ß/Smad2/3P pathway. Additionally, the excessive mechanical compression, applied in the presence of proinflammatory conditions diminishes the expression of the type II TGF-ß receptor, a receptor critical for maintenance of articular cartilage.

The Effect of Door Openings on Numbers of Colony Forming Units in the Operating Room during Hip Revision Surgery.

BACKGROUND: The aim of this study was to investigate the effect of door opening rates on air quality in the operation room during hip revision surgery by measuring the number of colony forming units per cubic meter (CFU/m(3)). METHODS: During 70 hip revision operations the number of CFU/m(3) was measured at four time points. Factors that may influence air quality were recorded, including the number of persons present, duration of surgery, and door opening rates. The measured CFU/m(3) was dichotomized as either acceptable (≤20 CFU/m(3)) or not acceptable (>20 CFU/m(3)). To determine whether door openings were associated with CFU/m(3) values, we used generalized linear mixed models to model the dichotomized repeatedly measured CFU/m(3) values. RESULTS: The median number of door openings per operation was eight (range, 0-72), the median duration of surgery was 145 min (range, 60-285), and the median number of persons present during surgery was eight (range, 5-10). Adjusted for number of persons in the operation room and duration of surgery, the number of door openings per operation was associated (odds ratio [OR] 1.05 [95% confidence interval {CI} 1.02-1.09]; p = 0.003) with an unacceptable number of CFU/m(3). CONCLUSIONS: In conclusion, a substantial association between number of door openings and an unacceptable number (>20) of CFU/m(3) was found. Adjusted for number of persons in the operation room and duration of surgery, every door opening increased the odds of unacceptable CFU/m(3) values by 5%. Number of persons present during surgery and duration of surgery were not related to CFU/m(3).

Societal and Economic Effect of Meniscus Scaffold Procedures for Irreparable Meniscus Injuries.

BACKGROUND: Meniscus scaffolds are currently evaluated clinically for their efficacy in preventing the development of osteoarthritis as well as for their efficacy in treating patients with chronic symptoms. Procedural costs, therapeutic consequences, clinical efficacy, and future events should all be considered to maximize the monetary value of this intervention. PURPOSE: To examine the socioeconomic effect of treating patients with irreparable medial meniscus injuries with a meniscus scaffold. STUDY DESIGN: Economic and decision analysis; Level of evidence, 2. METHODS: Two Markov simulation models for patients with an irreparable medial meniscus injury were developed. Model 1 was used to investigate the lifetime cost-effectiveness of a meniscus scaffold compared with standard partial meniscectomy by the possibility of preventing the development of osteoarthritis. Model 2 was used to investigate the short-term (5-year) cost-effectiveness of a meniscus scaffold compared with standard partial meniscectomy by alleviating clinical symptoms, specifically in chronic patients with previous meniscus surgery. For both models, probabilistic Monte Carlo simulations were applied. Treatment effectiveness was expressed as quality-adjusted life-years (QALYs), while costs (estimated in euros) were assessed from a societal perspective. We assumed €20,000 as a reference value for the willingness to pay per QALY. Next, comprehensive sensitivity analyses were performed to identify the most influential variables on the cost-effectiveness of meniscus scaffolds. RESULTS: Model 1 demonstrated an incremental cost-effectiveness ratio of a meniscus scaffold treatment of €54,463 per QALY (€5991/0.112). A threshold analysis demonstrated that a meniscus scaffold should offer a relative risk reduction of at least 0.34 to become cost-effective, assuming a willingness to pay of €20,000. Decreasing the costs of the meniscus scaffold procedure by 33% (€10,160 instead of €15,233; an absolute change of €5073) resulted in an incremental cost-effectiveness ratio of €7876 per QALY. Model 2 demonstrated an incremental cost-effectiveness ratio of a meniscus scaffold treatment of €297,727 per QALY (€9825/0.033). On the basis of the current efficacy data, a meniscus scaffold provides a relative risk reduction of "limited benefit" postoperatively of 0.37 compared with standard treatment. A threshold analysis revealed that assuming a willingness to pay of €20,000, a meniscus scaffold would not be cost-effective within a period of 5 years. Most influential variables on the cost-effectiveness of meniscus scaffolds were the cost of the scaffold procedure, cost associated with osteoarthritis, and quality of life before and after the scaffold procedure. CONCLUSION: Results of the current health technology assessment emphasize that the monetary value of meniscus scaffold procedures is very much dependent on a number of influential variables. Therefore, before implementing the technology in the health care system, it is important to critically assess these variables in a relevant context. The models can be improved as additional clinical data regarding the efficacy of the meniscus scaffold become available.

An experimental study to investigate biomechanical aspects of the initial stability of press-fit implants.

Initial fixation of press-fit implants depends on interference fit, surface morphology, and bone material properties. To understand the biomechanical effect of each factor and their interactions, the pull-out strength of seven types of CoCrMo tapered implants, with four different interference fits, three different surface morphologies (low, medium and high roughness), and at two time points (0 and 30 min) were tested in trabecular bone with varying density. The effect of interference fit on pull-out strength depended on the surface morphology and time. In contrast with our expectations, samples with a higher roughness had a lower pull-out strength. We found a similar magnitude of bone damage for the different surface morphologies, but the type of damage was different, with bone compaction versus bone abrasion for low and high frictional surfaces, respectively. This explains a reduced sensitivity of fixation strength to bone mineral density in the latter group. In addition, a reduction in fixation strength after a waiting period only occurred for the low frictional specimens. Our study demonstrates that it is essential to evaluate the interplay between different factors and emphasizes the importance of testing in natural bone in order to optimize the initial stability of press-fit implants.

Porous titanium particles for acetabular reconstruction in total hip replacement show extensive bony armoring after 15 weeks. A loaded in vivo study in 10 goats.

BACKGROUND AND PURPOSE: The bone impaction grafting technique restores bone defects in total hip replacement. Porous titanium particles (TiPs) are deformable, like bone particles, and offer better primary stability. We addressed the following questions in this animal study: are impacted TiPs osteoconductive under loaded conditions; do released micro-particles accelerate wear; and are systemic titanium blood levels elevated after implantation of TiPs? ANIMALS AND METHODS: An AAOS type-III defect was created in the right acetabulum of 10 goats weighing 63 (SD 6) kg, and reconstructed with calcium phosphate-coated TiPs and a cemented polyethylene cup. A stem with a cobalt chrome head was cemented in the femur. The goats were killed after 15 weeks. Blood samples were taken pre- and postoperatively. RESULTS: The TiP-graft layer measured 5.6 (SD 0.8) mm with a mean bone ingrowth distance of 2.8 (SD 0.8) mm. Cement penetrated 0.9 (0.3-1.9) mm into the TiPs. 1 reconstruction showed minimal cement penetration (0.3 mm) and failed at the cement-TiP interface. There were no signs of accelerated wear, metallic particle debris, or osteolysis. Median systemic titanium concentrations increased on a log-linear scale from 0.5 (0.3-1.1) parts per billion (ppb) to 0.9 (0.5-2.8) ppb (p=0.01). INTERPRETATION: Adequate cement pressurization is advocated for impaction grafting with TiPs. After implantation, calcium phosphate-coated TiPs were osteoconductive under loaded conditions and caused an increase in systemic titanium concentrations. However, absolute levels remained low. There were no signs of accelerated wear. A clinical pilot study should be performed to prove that application in humans is safe in the long term.

Biomaterials in search of a meniscus substitute.

The menisci fulfill key biomechanical functions in the tibiofemoral (knee) joint. Unfortunately meniscal injuries are quite common and most often treated by (partial) meniscectomy. However, some patients experience enduring symptoms, and, more importantly, it leads to an increased risk for symptomatic osteoarthritis. Over the past decades, researchers have put effort in developing a meniscal substitute able to prevent osteoarthritis and treat enduring clinical symptoms. Grossly, two categories of substitutes are observed: First, a resorbable scaffold mimicking biomechanical function which slowly degrades while tissue regeneration and organization is promoted. Second, a non resorbable, permanent implant which mimics the biomechanical function of the native meniscus. Numerous biomaterials with different (material) properties have been used in order to provide such a substitute. Nevertheless, a clinically applicable cartilage protecting material is not yet emerged. In the current review we provide an overview, and discuss, these different materials and extract recommendations regarding material properties for future developmental research.

Similar hyaline-like cartilage repair of osteochondral defects in rabbits using isotropic and anisotropic collagen scaffolds.

Lesions in knee joint articular cartilage (AC) have limited repair capacity. Many clinically available treatments induce a fibrous-like cartilage repair instead of hyaline cartilage. To induce hyaline cartilage repair, we hypothesized that type I collagen scaffolds with fibers aligned perpendicular to the AC surface would result in qualitatively better tissue repair due to a guided cellular influx from the subchondral bone. By specific freezing protocols, type I collagen scaffolds with isotropic and anisotropic fiber architectures were produced. Rabbits were operated on bilaterally and two full thickness defects were created in each knee joint. The defects were filled with (1) an isotropic scaffold, (2) an anisotropic scaffold with pores parallel to the cartilage surface, and (3) an anisotropic scaffold with pores perpendicular to the cartilage surface. Empty defects served as controls. After 4 (n=13) and 12 (n=13) weeks, regeneration was scored qualitatively and quantitatively using histological analysis and a modified O'Driscoll score. After 4 weeks, all defects were completely filled with partially differentiated hyaline cartilage tissue. No differences in O'Driscoll scores were measured between empty defects and scaffold types. After 12 weeks, all treatments led to hyaline cartilage repair visualized by increased glycosaminoglycan staining. Total scores were significantly increased for parallel anisotropic and empty defects over time (p<0.05). The results indicate that collagen scaffolds allow the formation of hyaline-like cartilage repair. Fiber architecture had no effect on cartilage repair.

Better primary stability with porous titanium particles than with bone particles in cemented impaction grafting: an in vitro study in synthetic acetabula.

AIMS: Impaction bone grafting creates new bone stock after hip joint replacement. Utilizing a synthetic bone substitute instead of bone might increase primary stability and is not associated with graft shortage and pathogen transmission. This study compares the initial stability of a graft layer of porous titanium particles (TiP), cancellous bone particles, and a 1:2 bone-titanium mix in synthetic cemented acetabular reconstructions. Displacement was measured by radiostereometric analysis after cyclic loading (1 Hz, maximum stress 2.5 MPa). Shear stress resistance was quantified by a lever out test of the cup. Cement penetration was quantified from cross-sections. FINDINGS: Titanium reconstructions showed less residual displacement (0.13 ± 0.13 mm) than pure bone particle reconstructions (0.57 ± 0.18 mm) (p < 0.01). Titanium reconstructions were also more resistant to shear stress (p < 0.001). The bone-titanium mix showed intermediate results. Cement penetrated deeper into the bone particle graft layers (4.8 ± 0.7) than into the titanium graft layers (3.8 ± 0.5 mm) (p < 0.02). CONCLUSIONS: Cemented acetabular revision reconstructions with porous TiP show better initial stability despite less cement penetration than bone particle reconstructions. Realistic preclinical in vivo testing should explore the hypothesis that porous TiP offer a safe alternative to the current gold standard of bone grafts.

Platelet-rich plasma can replace fetal bovine serum in human meniscus cell cultures.

Concerns over fetal bovine serum (FBS) limit the clinical application of cultured tissue-engineered constructs. Therefore, we investigated if platelet-rich plasma (PRP) can fully replace FBS for meniscus tissue engineering purposes. Human PRP and platelet-poor plasma (PPP) were isolated from three healthy adult donors. Human meniscal fibrochondrocytes (MFCs) were isolated from resected tissue after a partial meniscectomy on a young patient. Passage-4 MFCs were cultured in monolayer for 24 h, and 3 and 7 days. Six different culture media were used containing different amounts of either PRP or PPP and compared to a medium containing 10% FBS. dsDNA was quantified, and gene expression levels of collagen types I and II and aggrecan were measured at different time points with quantitative polymerase chain reaction in the cultured MFCs. After 7 days, the dsDNA quantity was significantly higher in MFCs cultured in 10% and 20% PRP compared to the other PRP and PPP conditions, but equal to 10% FBS. Collagen type I expression was lower in MFCs cultured with medium containing 5% PRP, 10% and 20% PPP compared to FBS. When medium with 10% PRP or 20% PRP was used, expressions were not significantly different from medium containing 10% FBS. Collagen type II expression was absent in all medium conditions. Aggrecan expression did not show differences between the different media used. However, after 7 days a higher aggrecan expression was measured in most culture conditions, except for 5% PRP, which was similar compared to FBS. Statistical significance was found between donors at various time points in DNA quantification and gene expression, but the same donors were not statistically different in all conditions. At 7 days cell cultured with 10% PRP and 20% PRP showed a higher density, with large areas of clusters, compared to other conditions. In an MFC culture medium, FBS can be replaced by 10% PRP or 20% PRP without altering proliferation and gene expression of human MFCs.

[Treatment of cartilaginous defects in the knee: recommendations from the Dutch Orthopaedic Association]. / Behandeling van kraakbeendefecten in de knie: advies van de Nederlandse Orthopaedische Vereniging.

Cartilaginous defects in the knee occur frequently and can cause the patient considerable limitations. They are diagnosed and classified by means of MRI and arthroscopy. The surgical options available to treat deep chondral lesions include bone marrow stimulation techniques (microfracture treatment), chondrocyte therapies (autologous chondrocyte implantation) and tissue replacement therapies (osteochondral autologous transplantation). Microfracture treatment and osteochondral autologous transplantation are suitable for treating chondral lesions that extend to the subchondral bone and are smaller than 2 and 4 cm2, respectively. Autologous chondrocyte implantation is a suitable method for treating single symptomatic chondral lesions larger than 2 cm2 in adults up to 50 years of age. There are no significant differences regarding the effectiveness of microfracture treatment, autologous chondrocyte implantation and osteochondral autologous transplantation for small defects: all show good clinical and functional short- and medium-term results. New second- and third-generation autologous chondrocyte implantation techniques seem to yield more sustainable tissue repair and better clinical long-term results for lesions larger than 4 cm2 in comparison to microfracture treatment.