Tissue adhesives for meniscus tear repair: an overview of current advances and prospects for future clinical solutions.

Menisci are crucial structures in the knee joint as they play important functions in load transfer, maintaining joint stability and in homeostasis of articular cartilage. Unfortunately, ones of the most frequently occurring knee injuries are meniscal tears. Particularly tears in the avascular zone of the meniscus usually do not heal spontaneously and lead to pain, swelling and locking of the knee joint. Eventually, after a (partial) meniscectomy, they will lead to osteoarthritis. Current treatment modalities to repair tears and by that restore the integrity of the native meniscus still carry their drawbacks and a new robust solution is desired. A strong tissue adhesive could provide such a solution and could potentially improve on sutures, which are the current gold standard. Moreover, a glue could serve as a carrier for biological compounds known to enhance tissue healing. Only few tissue adhesives, e.g., Dermabond(®) and fibrin glue, are already successfully used in clinical practice for other applications, but are not considered suitable for gluing meniscus tissue due to their sub-optimal mechanical properties or toxicity. There is a growing interest and research field focusing on the development of novel polymer-based tissue adhesives, but up to now, there is no material specially designed for the repair of meniscal tears. In this review, we discuss the current clinical gold standard treatment of meniscal tears and present an overview of new developments in this field. Moreover, we discuss the properties of different tissue adhesives for their potential use in meniscal tear repair. Finally, we formulate recommendations regarding the design criteria of material properties and adhesive strength for clinically applicable glues for meniscal tears.

Functional biomechanical performance of a novel anatomically shaped polycarbonate urethane total meniscus replacement.

PURPOSE: To evaluate the functional biomechanical performance of a novel anatomically shaped, polycarbonate urethane total meniscus implant. METHODS: Five human cadaveric knees were flexed between 0° and 90° under compressive loads mimicking a squat movement. Anteroposterior (AP) laxity tests were performed in 30° and 90° flexion. Meniscal kinematics and knee laxity were quantified using roentgen stereophotogrammetric analysis. Tibial cartilage contact mechanics were determined in 90° flexion. Measurements were repeated for the native medial meniscus, the implant, after total medial meniscectomy and allograft transplantation. RESULTS: The implant and allograft displayed increased posterior and medial displacements compared to the native meniscus, yet no differences were found between the implant and allograft. Meniscal condition did not affect rotational laxity. Compared to the native joint, AP laxity for the implant was increased in 30° flexion, but not in 90°. The implant reduced the mean contact pressure compared to meniscectomy but could not restore contact pressures to native meniscus levels. Compared to the native meniscus, the implant significantly increased the peak pressure, while the contact area was reduced. Contact mechanics of the implant and allograft were never statistically different. CONCLUSIONS: Biomechanical performance was similar for the implant and allograft. However, both meniscal replacements could not restore outcomes to native meniscus levels or sufficiently improve outcomes after meniscectomy. This was presumably caused by the mobility allowed by the suture-only horn fixation. The similarity of implant and allograft performance suggests that the novel implant has the biomechanical potential to serve as an alternative to meniscal allograft transplantation.

Biological activity of tri-calciumphosphate/hydroxyl-apatite granules mixed with impacted morsellized bone graft. A study in rabbits.

Reconstruction of bone defects with impacted morsellized cancellous bone grafts (MCB) is a popular method. Because of a shortage of human bone, mixing with biomaterials may be attractive. Ceramics may be used as bone graft extenders. In this study, various volume mixtures of biphasic tri-calciumphosphate/hydroxyl-apatite (TCP-HA) granules (1.5-2 mm) with MCB were examined in a non-loaded defect model in rabbits. Direct post-operatively, many 10-150 microm TCP-HA particles were present due to impaction. Irrespective to the group, after 8 weeks, virtually all MCB was resorbed and most TCP-HA granules were osseous-integrated with newly formed bone. The cross-sectional areas of TCP-HA after 8 weeks was generally smaller compared with direct post-operatively and the number of small 10-150 microm TCP-HA particles seemed reduced. Macrophages and giant cells were sparse after 8 weeks. In conclusion, the osteoconductivity of various mixtures of MCB and TCP-HA granules is not dependent on the ratio of TCP-HA over MCB. The reduced number of the 10-150microm TCP-HA particles after 8 weeks, may suggest that a cellular mediated resorption process of TCP-HA granules took place. Based on these favorable biological findings subsequent in-vivo experiments are warranted in load-bearing conditions to investigate whether these findings hold for joint reconstruction purposes.

Evaluation of novel biodegradable three-armed- and hyper-branched tissue adhesives in a meniscus explant model.

Current treatment methods to repair meniscal tears do not bring fully satisfactory results. Tissue adhesives are considered promising alternatives, since they are easy to apply and cause minimal tissue trauma. The first aim of this study was to analyze the adhesive properties of and tissue response to two recently developed biodegradable block copolymeric three-armed- and hyper-branched tissue adhesives. The second aim was to investigate if tissue surface modification with collagenase improves the attachment of the adhesives and increases the healing potential of the tissue. Cylindrical explants were harvested from bovine menisci. The central core of the explants was removed and glued back into the defect, with or without incubation in collagenase solution prior to gluing, using one of the novel glues, Dermabond® or fibrin glue. The repair constructs were cultured in vitro for 1 and 28 days. Adhesion tests and histology were performed to analyze the effects of the glue in combination with the additional treatment. The adhesive strength of the novel glues was 40-50 kPa, which was significantly higher than that of fibrin glue (15 kPa). Cells were present in direct contact with the glues, and the tissue remained vital during the whole culture period. Increased cellularity around the tear in the collagenase treated explants was observed after 1 day. The two newly developed tissue adhesives are attractive materials to be used for repair of meniscal tears. The beneficial influence of collagenase treatment in treating meniscal tears with glues still needs to be confirmed in more clinical relevant studies. © 2017 Wiley Periodicals, Inc. J Biomed Mater Res Part A: 105A: 1405-1411, 2017.

Meniscal replacement in dogs. Tissue regeneration in two different materials with similar properties.

In earlier studies, meniscal replacement with a porous polymer implant led to regeneration of neo-meniscal tissue. To evaluate the influence of the chemical properties on the tissue regeneration in the implant, in the present study, the meniscus in the dog's knee was replaced with either an aromatic 4,4-diphenylmethanediisocyanate based polyesterurethane implant (Estane) (n = 6) or with an aliphatic 1,4-butanediisocyanate based polyesterurethane implant (PCLPU) (n = 6). After 6 months, the knee joints were resected and the tissue behavior in the two different prostheses was evaluated microscopically. In both prostheses, a meniscus-like distribution of the tissue phenotype was found with collagen type I in the peripheral fibrous zones and collagen type II in the central, more cartilaginous zones. The compression-stress behavior of the implant-tissue construct remained in between the stiffness of the polymer material and that of the native meniscus. The PCLPU implant seemed to provoke less synovial tissue reaction. After meniscectomy solely, in 5 out of 6 cases, a meniscus-like regenerate was formed. Furthermore, the articular cartilage degeneration after placing a PCLPU implant did also not exceed the degeneration after the Estane implant or after meniscectomy. The differences between these two implants did not seem to influence the tissue regeneration in the implant. However, PCLPU seemed to evoke less tissue reaction and, therefore, is thought to be less or even nontoxic as compared with the Estane implant. Therefore, for studies in the future, the authors prefer the PCLPU prostheses for replacement of the meniscus.

Development of biodegradable hyper-branched tissue adhesives for the repair of meniscus tears.

Meniscus tears are one of the most commonly occurring injuries of the knee joint. Current meniscus repair techniques are challenging and do not bring fully satisfactory results. Tissue adhesives are a promising alternative, since they are easy to apply and cause minimal tissue trauma. In this study, a series of amphiphilic copolymers based on polyethylene glycol, trimethylene carbonate and citric acid were synthesized and subsequently end-functionalized with hexamethylene diisocyanate to form reactive adhesive materials. The shear adhesive strength of the networks to bovine meniscus tissue measured in a lap-shear adhesion test ranged between 20 and 80 kPa, which was better than for fibrin glue (10 kPa). The elastic modulus of the networks depended on composition and was in the same range as that of human meniscus. Cell compatibility was assessed using Alamar Blue staining after incubation of the bovine meniscus cells with different concentrations of the glues for 7 days. Cell viability was not affected after adding up to 3mg of the adhesive/mL of medium. The proposed materials are suitable candidates to be used as resorbable tissue adhesives for meniscus repair. They have excellent mechanical and adhesive properties that can be adjusted by varying the composition of the copolymers. STATEMENT OF SIGNIFICANCE: Meniscal tears often occur and current treatment strategies do not bring fully satisfactory results. Use of biodegradable tissue adhesives would be an interesting option, but currently available adhesives are not suited due to toxicity or poor mechanical properties. Here, we describe the development of novel biodegradable, hyper-branched, adhesive copolymers. These adhesives cure upon contact with water forming flexible networks. Their adhesion to bovine meniscus tissue was significantly better than that of clinically used fibrin glue. The tensile properties of the cured networks were in the same range of values of the human meniscus. When physiologically relevant amounts were added to cells in culture, not toxic effects were observed. Therefore, the proposed materials are interesting resorbable tissue adhesives for meniscus repair.

Cemented cup stability during lever-out testing after acetabular bone impaction grafting with bone graft substitutes mixes containing morselized cancellous bone and tricalcium phosphate--hydroxyapatite granules.

Bone defects after failed total hip arthroplasty can be reconstructed with impacted morselized bone grafts and a cemented cup. In the near future the amount of bone grafts available for surgical purposes will be insufficient. Ceramic calcium phosphates [tricalcium phosphate (TCP) and hydroxyapatite (HA)] have been widely considered as potential bone graft substitutes or bone graft extenders. In the past, mechanical experiments have been performed to determine implant stability of bone grafts and ceramic TCP-HA granules mixes under a compressive load. However, in-vivo migration studies suggest that shear loading may be equally important. This in-vitro study investigated the initial stability of cups reconstructed with various mixes of bone grafts and ceramic TCP-HA granules in a lever-out situation, where shearing is the predominant loading mode. It was found that the cups reconstructed with mixes of bone graft and TCP-HA granules exhibited greater mechanical stability than the cups reconstructed with bone grafts only. It is concluded that from a mechanical standpoint, when considering shear force resistance, 50-50 per cent volume mix and 25-75 per cent volume mix of morselized cancellous bone graft and TCP-HA granules both provide adequate initial cup stability and can be used for acetabular reconstructions with the bone impaction grafting technique.

Short Term Evaluation of an Anatomically Shaped Polycarbonate Urethane Total Meniscus Replacement in a Goat Model.

PURPOSE: Since the treatment options for symptomatic total meniscectomy patients are still limited, an anatomically shaped, polycarbonate urethane (PCU), total meniscus replacement was developed. This study evaluates the in vivo performance of the implant in a goat model, with a specific focus on the implant location in the joint, geometrical integrity of the implant and the effect of the implant on synovial membrane and articular cartilage histopathological condition. METHODS: The right medial meniscus of seven Saanen goats was replaced by the implant. Sham surgery (transection of the MCL, arthrotomy and MCL suturing) was performed in six animals. The contralateral knee joints of both groups served as control groups. After three months follow-up the following aspects of implant performance were evaluated: implant position, implant deformation and the histopathological condition of the synovium and cartilage. RESULTS: Implant geometry was well maintained during the three month implantation period. No signs of PCU wear were found and the implant did not induce an inflammatory response in the knee joint. In all animals, implant fixation was compromised due to suture breakage, wear or elongation, likely causing the increase in extrusion observed in the implant group. Both the femoral cartilage and tibial cartilage in direct contact with the implant showed increased damage compared to the sham and sham-control groups. CONCLUSION: This study demonstrates that the novel, anatomically shaped PCU total meniscal replacement is biocompatible and resistant to three months of physiological loading. Failure of the fixation sutures may have increased implant mobility, which probably induced implant extrusion and potentially stimulated cartilage degeneration. Evidently, redesigning the fixation method is necessary. Future animal studies should evaluate the improved fixation method and compare implant performance to current treatment standards, such as allografts.

Ultrastructural localization of adrenocorticotrophic hormone and the phosphoprotein B-50/growth-associated protein 43 in freeze-substituted, Lowicryl HM20-embedded mesencephalic central gray substance of the rat.

Previous studies have shown that the endogenous phosphorylation of the neuron-specific protein B-50 in isolated synaptic plasma membranes is inhibited by adrenocorticotrophic hormone(1-24). The aim of this study is to examine if there is a specific neuroanatomical interaction of adrenocorticotrophic hormone and B-50 in the mesencephalic central gray substance of the rat. With light microscopy, high B-50 immunoreactivity was detected throughout the mesencephalic central gray substance, overlapping with those areas where adrenocorticotrophic hormone-immunoreactive fibres were present. To study the ultrastructural localization of B-50 and adrenocorticotrophic hormone, we employed a method of immunogold labelling on ultrathin sections of freeze-substituted and Lowicryl HM20-embedded fixed brain tissue. This offered optimal morphological preservation together with high retention of antigenicity. At the electron microscopic level, adrenocorticotrophic hormone immunoreactivity was detected in dense-core secretory granules present in non-junctional regions of axoinal varicosities. This suggests a non-synaptic release of adrenocorticotrophic hormone from the axons. Using double immunolabelling techniques we showed that in adrenocorticotrophic hormone-innervated areas of the mesencephalic central gray substance B-50 immunoreactivity was present at plasma membranes of all unmyelinated axons and axonal varicosities and virtually absent in dendrites. The result on B-50 localization agrees well with previous studies in the hippocampus [Van Lookeren Campagne et al. 1990 J. Neurocytol. 19, 948-961] and in the pyramidal tract [Gorgels et al. 1989 J. Neurosci. 9, 3861-3869] of the rat and suggests that in the mature rat central nervous system, B-50 expression in axons is a general phenomenon. For the adrenocorticotrophic hormone-innervated areas, we discuss the proposal that non-synaptically released adrenocorticotrophic hormone modulates B-50 phosphorylation in axons and axon terminals.

Scintigraphic evaluation of experimental chronic osteomyelitis.

UNLABELLED: Assessment of disease activity and disease extent in chronic osteomyelitis remains a difficult diagnostic problem. Radiography is not particularly sensitive. Scintigraphic techniques can be more helpful, but the routinely available agents lack specificity (99mTc-methylene diphosphonate [MDP], 67Ga-citrate) or are laborious to prepare (111In-leukocytes). We evaluated the performance of 2 new radiopharmaceuticals, 99mTc-polyethyleneglycol (PEG) liposomes and 99mTc-hydrazinonicotinamide (HYNIC)-immunoglobulin G (IgG), in an experimental model of chronic osteomyelitis. METHODS: Chronic osteomyelitis was induced in rabbits by inserting S. aureus into the right reamed and washed femoral canal. The canal was closed with cement. A sham operation was performed on the left femur. Routine radiographs were obtained immediately after surgery and before scintigraphy. Four weeks after surgery, each rabbit was injected with 37 MBq 99mTc-PEG liposomes, 99mTc-HYNIC-IgG, and 99mTc-MDP on 3 consecutive days and imaged up to 4 (MDP) or 22 (liposomes and IgG) h after injection. On day 4, rabbits received either 18 MBq 111In-granulocytes or 67Ga-citrate and were imaged up to 44 h after injection. Uptake in the infected femur was determined by drawing regions of interest. Ratios of infected-to-sham-operated femur were calculated. After the last image, the rabbits were killed, and the left and right femur were scored for microbiologic and histopathologic evidence of osteomyelitis. RESULTS: 99mTc-PEG liposomes and 99mTc-HYNIC-IgG correctly identified all 6 rabbits with osteomyelitis. 11In-granulocytes and 67Ga-citrate gave equivocal results in 1 infected rabbit. 99mTc-MDP missed 1 case of osteomyelitis. The uptake in the affected region did not differ significantly between the agents, although 99mTc-MDP tended to have higher values (MDP, 4.75 +/- 1.23 percentage injected dose per gram [%ID/g]; 67Ga, 2.05 +/- 0.54 %ID/g; granulocytes, 1.56 +/- 0.83 %ID/g; liposomes, 1.75 +/- 0.76 %ID/g, and IgG, 1.96 +/- 0.27 %ID/g). The ratios of infected-to-normal femur were also not significantly different for the respective radiopharmaceuticals. Radiography visualized only severe osteomyelitis. CONCLUSION: In this rabbit model, 99mTc-PEG liposomes and 99mTc-HYNIC-IgG performed at least as well as 111In-granulocytes and 67Ga-citrate in the localization of chronic osteomyelitis. The ease of preparation, the better image quality, and the lower radiation dose suggest that 99mTc-PEG liposomes and 99mTc-HYNIC-IgG might be suitable alternatives for 67Ga-citrate and 111In-granulocytes in the scintigraphic evaluation of osteomyelitis.

Biomechanical and histological evaluation of a hydroxyapatite-coated titanium femoral stem fixed with an intramedullary morsellized bone grafting technique: an animal experiment on goats.

To reconstruct femoral intramedullary bone-stock loss in revision surgery of failed total hip arthro-plasties, morsellized trabecular bone grafts can be used. In 14 goats a noncemented hydroxyapatite-coated titanium stem was fixed within a circumferential construction of bone allografts. After 6 or 12 wk, four goats were used for mechanical tests and three for histology. The stability of the stems relative to the bone was determined in a loading experiment with Roentgenstereo-Photogrammatic Analysis (RSA). Owing to two loosenings and two fractures, only one 6-wk specimen and three 12-wk specimens were available for mechanical testing. The prostheses were very stable at 12 wk. The most important movements were axial rotation (maximal 0.17 degrees at 800 N) and subsidence (maximal 0.036 mm at 800 N). After unloading, there was 40-60% elastic recovery. Histological examination showed revascularization and remodelling of the graft in all the specimens investigated. At the graft site, bone apposition and bone resorption had resulted in a mixture of graft and new bone. Bone incorporation was mainly seen in the proximal areas. Graft lysis was evident in the midshaft region and at distal levels around the prostheses.

Acetabular defect reconstruction with impacted morsellized bone grafts or TCP/HA particles. A study on the mechanical stability of cemented cups in an artificial acetabulum model.

In revision surgery of the acetabulum bone defects can be filled with impacted human morsellized bone grafts. Because of a worldwide limited availability of human bone, alternatives are being considered. In this study we compared the initial stability of acetabular cups after reconstructing a cavitary defect with various compositions of impacted tricalciumphosphate-hydroxyapatite (TCP/HA) particles and mixes of TCP/HA particles and human grafts in a realistic acetabulum model. Primary cemented cups and reconstructions with impacted human cancellous grafts were used as reference. A dynamic load displaced the acetabular cups superomedially. The primary cemented cups showed the highest stability. The cups with impacted human grafts produced the most displacement. All reconstructions with the TCP/HA particles showed a high stability of the cups. However, especially when using large TCP/HA particles this was probably due to a large amount of cement penetration. Mixing TCP/HA particles with human grafts seemed to decrease cement penetration. although still a high stability was obtained. In this perspective, we concluded that TCP/HA particles might be useful as a bone graft extender in the reconstruction of acetabular bone defects.

Incorporation of morsellized bone graft under controlled loading conditions. A new animal model in the goat.

The aim of this study was to develop a new animal model in which we could assess the in vivo effects of mechanical stimuli in the incorporation process of impacted morsellized bone grafts. The subcutaneous pressure implant SPI was developed for use in the goat. This device can generate controlled loading conditions onto a fixed amount of bone graft in the distal femur. Twenty goats were divided into three groups: non-loaded, 2 or 4 MPa loads (1 Hz, 1 h/day). The goats were sacrificed after 3, 6 or 12 weeks. The results were documented by clinical observations, quantitative bone density from QCT-scanning and histomorphometry. Nine post-mortem knee specimens were prepared in a similar manner to the experimental knees to determine the reproducibility and mechanical stability of the grafting method. Three goats were lost due to complications, the others functioned clinically well. Histology showed invasion of the bone graft by a front of vascular fibrous tissue after which osteoclasts resorbed the dead bone graft, followed by woven bone apposition on the graft remnants. At 12 weeks the loaded grafts had transformed into a vital trabecular structure. QCT bone density measurements revealed persistently high densities in the 12-weeks 4 MPa specimens, but reduced densities in the 2 MPa and non-loaded specimens. Morphometrically, the mineralising surface was larger in the 4 MPa group (P = 0.02) and the incorporation and remodelling processes had advanced more rapidly in the 2 MPa specimens (P = 0.04). Although the numbers investigated in this study in each group were low, statistical differences were found in the amount of graft left after incorporation and in the apposition rate of the new bone. In the future this model will be used to study the incorporation potential of different types of bone graft and bone graft substitutes.

A porous polymer scaffold for meniscal lesion repair--a study in dogs.

Meniscal lesions often occur in the avascular area of the meniscus with little chance of spontaneous repair. An access channel in the meniscal tissue can function as an entrance for ingrowing repair tissue from the vascular periphery of the meniscus to the lesion in the avascular zone which again induced healing of the lesion. Implantation of a porous polymer in a full-thickness access channel induced healing. However, a better integration between meniscal tissue and the implant might be achieved with the combination of the newly developed porous polymers and a modified surgical technique. This might improve meniscal lesion healing and the repair of the access channel with neo-meniscal tissue. Longitudinal lesions were created in the avascular part of 24 canine lateral menisci and a partial-thickness access channel was formed to connect the lesion with the meniscal periphery. In 12 menisci, the access channel was left empty (control group), while in the remaining 12 menisci the polymer implant was sutured into the access channel. Repair of the longitudinal lesions was achieved with and without polymer implantation in the partial-thickness access channel. Polymer implants induced fibrous ingrowth with cartilaginous areas, which resembled neo-meniscal tissue. Implantation did not prevent articular cartilage degeneration.

Histological and biomechanical analysis of bone and interface reactions around hydroxyapatite-coated intramedullary implants of different stiffness: a pilot study on the goat.

We hypothesized that reduced stem stiffness of orthopaedic implants contributes to a high risk of loosening, since interface stresses and relative motions may exceed a tolerable range. To study this hypothesis, three types of load-bearing implant with different stiffnesses were inserted into the tibia of the goat. Histological analysis was performed of bone repair after insertion of the implant, bone ingrowth, interface disruption and loosening. A finite element model of the configuration provided the quantitative range of interface stresses and relative motions for the present experiment. The implants were made out of stainless steel, hollow titanium and a thin titanium core covered with a polyacetal coating. The stiffness ratios of these implants were approximately 10:4:1, respectively. All implants were coated with a layer of hydroxyapatite (HA) in order to minimize the possible biological effects of the different implant materials. Irrespective of the type of implant, there was a repair phase that lasted 6-12 weeks. The stiff implants functioned well. Large areas of bone bonding to the HA layer were found after the repair phase at 12 weeks postoperatively. After 24 weeks, some signs of loosening were observed. More loosening occurred with the hollow titanium and polyacetal implants, mainly during the repair phase. Three hollow titanium and three polyacetal coated implants survived this period, and were killed after 24 weeks. The integrity of the HA layer at the bone-implant interface of the titanium implants was good. In the polyacetal implants, the repair reaction of the cortical bone was incomplete. Bone ingrowth into HA was largely lacking. In conclusion, we found significant differences in the repair and interface reactions around implants of different stiffness. Stiff implants showed favourable initial interface conditions for bone ingrowth. Intermediate and flexible implants provoked unfavourable interface conditions for initial bone ingrowth. The finite element study showed that the flexible stems produce larger micromotions and higher interface stresses at the bone-prosthesis interface than the stiff stems, indicating an explanation for the histological findings.

Resurfacing potential of heterologous chondrocytes suspended in fibrin glue in large full-thickness defects of femoral articular cartilage: an experimental study in the goat.

A large full-thickness articular-cartilage defect was created in the medial femoral condyle of 32 adult goats. The defects were xenografted with isolated rabbit chondrocytes suspended in fibrin glue. Sham operated goats, where only a standardized defect was created, were used as controls. Results of cartilage repair were assessed after 3, 8, 13, 26 and 52 weeks. The repair tissue was evaluated macroscopically, histologically and biochemically. Results indicated that xenografted rabbit chondrocytes survived the transplantation and maintained their potential to produce matrix in fibrin glue, particularly if they were located in a non-weight-bearing area. In terms of an immunological reaction to xenografted chondrocytes, only mild signs of synovitis were observed in both groups and rejection of transplanted cells did not occur. From 3 weeks gradually progressive resolvement of the fibrin glue was observed with subsequent replacement by fibrous tissue. Initially xenografted defects histologically showed better tendency for cartilage regeneration, however, 52 weeks after surgery no significant differences could be detected in the repair tissue of both groups macroscopically, histologically and on biochemical scoring. The amount of collagen type II in the newly synthesized matrix was 75% 1 year after surgery. This study shows that isolated heterologous chondrocytes can be used for transplantation in articular cartilage defects, however, fibrin glue does not offer enough biomechanical support to the cells to maintain its function as a three-dimensional scaffold.

Linkage of chondroitin-sulfate to type I collagen scaffolds stimulates the bioactivity of seeded chondrocytes in vitro.

An increasing amount of interest is focused on the potential use of tissue-engineered articular cartilage implants, for repair of defects in the joint surface. In this perspective, various biodegradable scaffolds have been evaluated as a vehicle to deliver chondrocytes into a cartilage defect. This cell-matrix implant should eventually promote regeneration of the traumatized articular joint surface with hyaline cartilage. Successful regeneration can only be achieved with such a tissue-engineered cartilage implant if the seeded cells reveal an appropriate proliferation rate in the biodegradable scaffold together with the production of a new cartilage-specific extracellular matrix. These metabolic parameters can be influenced by the biochemical composition of a cell-delivery scaffold. Further elucidation of specific cell-matrix interactions is important to define the optimal biochemical composition of a cell-delivery vehicle for cartilage repair. In this in vitro study, we investigated the effect of the presence of cartilage-specific glycosaminoglycans in a type I collagen scaffold on the metabolic activity of seeded chondrocytes. Isolated bovine chondrocytes were cultured in porous type I collagen matrices in the presence and absence of covalently attached chondroitin sulfate (CS) up to 14 days. CS did indeed influence the bioactivity of the seeded chondrocytes. Cell proliferation and the total amount of proteoglycans retained in the matrix, were significantly higher (p < 0.001) in type I collagen scaffolds with CS. Light microscopy showed the formation of a more dense cartilaginous layer at the matrix periphery. Scanning electron microscopy revealed an almost complete surfacing of the initially porous surface of both matrices. Histology and reverse transcriptase PCR for various proteoglycan subtypes suggested a good preservation of the chondrocytic phenotype of the seeded cells during culture. The stimulatory potential of CS on both the cell-proliferation and matrix retention, turns this GAG into an interesting biochemical component of a cell-delivery scaffold for use in tissue-engineering articular cartilage.

Crosslinked type II collagen matrices: preparation, characterization, and potential for cartilage engineering.

The limited intrinsic repair capacity of articular cartilage has stimulated continuing efforts to develop tissue engineered analogues. Matrices composed of type II collagen and chondroitin sulfate (CS), the major constituents of hyaline cartilage, may create an appropriate environment for the generation of cartilage-like tissue. In this study, we prepared, characterized, and evaluated type 11 collagen matrices with and without CS. Type II collagen matrices were prepared using purified, pepsin-treated, type II collagen. Techniques applied to prepare type I collagen matrices were found unsuitable for type II collagen. Crosslinking of collagen and covalent attachment of CS was performed using 1-ethyl-3-(3-dimethyl aminopropyl)carbodiimide. Porous matrices were prepared by freezing and lyophilization, and their physico-chemical characteristics (degree of crosslinking, denaturing temperature, collagenase-resistance, amount of CS incorporated) established. Matrices were evaluated for their capacity to sustain chondrocyte proliferation and differentiation in vitro. After 7 d of culture, chondrocytes were mainly located at the periphery of the matrices. In contrast to type I collagen, type II collagen supported the distribution of cells throughout the matrix. After 14 d of culture, matrices were surfaced with a cartilagenous-like layer, and occasionally clusters of chondrocytes were present inside the matrix. Chondrocytes proliferated and differentiated as indicated by biochemical analyses, ultrastructural observations, and reverse transcriptase PCR for collagen types I, II and X. No major differences were observed with respect to the presence or absence of CS in the matrices.

Prosthetic replacement of the medial meniscus in cadaveric knees: does the prosthesis mimic the functional behavior of the native meniscus?

UNLABELLED: Meniscus replacement by a polymer meniscus prosthesis in dogs resulted in generation of new meniscal tissue. HYPOTHESIS: Optimal functioning of the prosthesis would involve realistic deformation and motion patterns of the prosthesis during knee joint motion. STUDY DESIGN: Controlled laboratory study. METHODS: The movements of the meniscus were determined during knee joint flexion and extension with and without internal and external tibial torque by means of roentgen stereophotogrammetric analysis. Subsequently, the meniscus in 6 human cadaveric knee joints was replaced by a meniscus prosthesis. RESULTS: All different parts of the meniscus showed a posterior displacement during knee joint flexion. The anterior horn was more mobile than the posterior horn. The prosthesis mimicked the movements of the meniscus. However, the excursions of the prosthesis on the tibial plateau were less. The knee joint laxity was not significantly higher after replacement with the meniscus prosthesis. CONCLUSIONS: The prosthesis approximated the behavior of the native meniscus. Improvement in both the gliding characteristics of the prosthetic material and the fixation of the prosthesis may improve the function. CLINICAL RELEVANCE: The meniscus prosthesis needs to be optimized to achieve a better initial function in the knee joint.

Acetabular reconstruction with impacted morsellised cancellous bone graft and cement. A 10- to 15-year follow-up of 60 revision arthroplasties.

We report a long-term review of 60 acetabular components revised using impacted, morsellised bone allografts and a cemented polyethylene cup. The acetabular defects were cavitary (37) or combined (23). Follow-up was for a mean 11.8 years (10 to 15). Further revision was needed in five hips, two for septic and three for aseptic loosening. The overall survival rate at 11.8 years was 90%; excluding the septic cases it was 94%. Acetabular reconstruction with impacted morsellised cancellous grafts and cement gives satisfactory long-term results.