The results for autologous chondrocyte implantation (ACI) in the treatment of osteochondral defects in the knee are encouraging. At present, two techniques have been described to retain the chondrocyte suspension within the defect. The first involves using a periosteal flap harvested from the distal femur and the second involves using a type I/III collagen membrane. To the authors' knowledge there are no comparative studies of these two techniques in the current literature. A total of 68 patients with a mean age of 30.52 years (range 15 to 52 years) with symptomatic articular cartilage defects were randomised to have either ACI with a periosteal cover (33 patients) or ACI with a type I/III collagen cover (35 patients). The mean defect size was 4.54 cm. 2. (range 1 to 12 cm. 2. ). All patients were followed up at 24 months. A functional assessment using the Modified Cincinnati score showed that 74% of patients had a good or excellent result following the ACI with collagen cover compared with 67% after the ACI with periosteum cover at 2 years (p>0.05). Arthroscopy at 1 year also demonstrated similar results for both techniques. However, 36.4% of the periosteum covered grafts required shaving for hypertrophy compared with 1 patient for the collagen covered technique. This prospective, randomised study has shown no statistical difference between the clinical outcome of ACI with a periosteal cover versus ACI with a collagen cover at 2 years. A significant number of patients who had the ACI with periosteum technique required shaving of a hypertrophied graft within the first year of surgery. We conclude that there is no advantage in using periosteum as a cover for retaining the chondrocytes within an osteochondral defect; as a result we advocate the use of an alternative cover such as a porcine-derived, type I/III collagen membrane

Background:. Different surgical approaches have been proposed for the treatment of chondral lesions. However surgical management of osteochondral defects of the knee joint involving subchondral bone are still under debate. Purpose:. The aim of this prospective non-randomized uncontrolled clinical investigation is to confirm the effectiveness of a commercially available biomimetic osteochondral scaffold in regenerating cartilage and subchondral bone of severe osteochondral lesions of the knee joint with one step surgery. Methods:. The biomimetic scaffold has a multilayer structure consisting of a combination of type I collagen and type I collagen/hydroxyapatite, mimicking the osteochondral connective tissue of the knee joint. From 2009 to 2011, sixty-one patients affected by grade III or IV osteochondral lesions of the knee, according to Outerbridge Classification, were admitted to three centers and received the biomimetic scaffold. Four-nine patients were evaluated using the International Knee Documentation Committee (IKDC), Tegner and VAS scores, and MRI at 1-, 2- and 3-year follow-ups. Biopsies were carried out in 5 patients at an average time of 19.2 months to histologically evaluate the quality of the newly-formed tissue. Results:. All patients tolerated the surgery well; no major adverse events were observed in the early postoperative period. Clinical evaluation of the 49 patients showed a statistically significant improvement in all scores at 1- 2- and 3-year follow-ups as compared to preoperative baseline scores. Improvement in the scores and functional recovery seemed to reach a plateau after 2 years; no significant improvement was seen between the 2- and the 3-year follow-up. Conclusions:. A synthetic biomimetic scaffold used in one-step surgery for the treatment of severe osteochondral knee lesions significantly improved symptoms and joint function, as demonstrated by subjective and objective scoring system evaluation. Furthermore, the athletic subpopulation exhibited a significantly better outcome than the non-athletic subpopulation

The zonal organization of articular cartilage is crucial in providing the tissue with mechanical properties to withstand compression and shearing force. Current treatments available for articular cartilage injury are not able to restore the hierarchically organized architecture of the tissue. Implantation of zonal chondrocyte as a multilayer tissue construct could overcome the limitation of current treatments. However, it is impeded by the lack of efficient zonal chondrocyte isolation protocol and dedifferentiation of chondrocytes during expansion on tissue culture plate (TCP). This study aims to develop a protocol to produce an adequate number of high-quality zonal chondrocytes for clinical application via size-based zonal chondrocyte separation using inertial spiral microchannel device and expansion under dynamic microcarrier culture. Full thickness (FT) chondrocytes isolated from porcine femoral condyle cartilage were subjected to two serial of size-based sorting into three subpopulations of different cell sizes, namely small (S1), medium (S2), and large (S3) chondrocytes. Zonal phenotype of the three subpopulations was characterised. To verify the benefit of stratified zonal chondrocyte implantation in the articular cartilage regeneration, a bilayer hydrogel construct composed of S1 chondrocytes overlaying a mixture of S2 and S3 (S2S3) chondrocytes was delivered to the rat osteochondral defect model. For chondrocyte expansion, two dynamic microcarrier cultures, sort-before-expansion and sort-after-expansion, which involved expansion after or before zonal cells sorting, were studied to identify the best sort-expansion strategy. Size-sorted zonal chondrocytes showed zone-specific characteristics in qRT-PCR with a high level of PRG4 expression in S1 and high level of aggrecan, Type II and IX collagen expression in S2 and S3. Cartilage reformation capability of sorted zonal chondrocytes in three-dimensional fibrin hydrogel showed a similar trend in qRT-PCR, histology, extracellular matrix protein quantification and mechanical compression test, indicating the zonal characteristics of S1, S2 and S3 as superficial (SZ), middle (MZ) and deep (DZ) zone chondrocytes, respectively. Implantation of bilayered zonal chondrocytes resulted in better cartilage tissue regeneration in a rat osteochondral defect model than FT control group, with predominantly Type II hyaline cartilage tissue and significantly lower Type I collagen. Dynamic microcarrier expansion of sorted zonal chondrocytes was able to retain the zonal cell size difference that correlate to zonal phenotype, while maintaining the rounded chondrocyte morphology and F-actin distribution similar to that in mature articular cartilage. With the better retention of zonal cell size and zonal phenotype relation on microcarrier, zonal cells separation was achievable in the sort-after-expansion strategy with cells expanded on microcarrier, in comparison to cells expanded on TCP. Inertial spiral microchannel device provides a label-free and high throughput method to separate zonal chondrocytes based on cell size. Stratified implantation of zonal chondrocytes has the potential to improve articular cartilage regeneration. Dynamic microcarrier culture allows for size-based zonal chondrocyte separation to be performed on expanded chondrocytes, thus overcoming the challenge of limited tissue availability from the patients. Our novel zonal chondrocyte isolation and expansion protocol provide a translatable strategy for stratified zonal chondrocyte implantation that could improve articular cartilage regeneration of critical size defects

The meniscus is comprised largely of type I collagen, as well as fibrochondrocytes and proteoglycans. In articular cartilage and intervertebral disc, proteoglycans make a significant contribution to mechanical stiffness of the tissue via negatively charged moieties which generate Donnan osmotic pressures. To date, such a role for proteoglycans in meniscal tissue has not been established. This study aimed to investigate whether meniscal proteoglycans contribute to mechanical stiffness of the tissue via electrostatic effects. Following local University Ethics Committee approval, discs of meniscal tissue two millimetres thick and of five millimetres diameter were obtained from 12 paired fresh frozen human menisci, from donors < 6 5 years of age, with no history of osteoarthritis or meniscal injury. Samples were taken from anterior, middle and posterior meniscal regions. Each disc was placed within a custom confined compression chamber, permeable at the top and bottom only and then bathed in one of three solutions − 0.14M PBS (mimics cellular environment), deionised water (negates effect of mobile ions) or 3M PBS (negates all ionic effects). The apparatus was mounted within a Bose Electroforce 3100 materials testing machine and a 0.3N preload was applied. The sample was allowed to reach equilibrium, before being subjected to a 10% ramp compressive strain followed by a 7200 second hold phase. Equal numbers of samples from each meniscus and meniscal region were tested in each solution. Resultant stress relaxation curves were fitted to a nonlinear poroviscoelastic model with strain dependent permeability using FEBio finite element modelling software. Goodness of fit (R2) was assessed using a coefficient of determination. All samples were assayed for proteoglycan content. Comparison of resultant mechanical parameters was undertaken using multivariate ANOVA with Bonferroni adjustment for multiple comparisons. 36 samples were tested. A significant difference (p < 0 .05) was observed in the value of the Young's modulus (E) between samples tested in deionised water compared to 0.14M/3M PBS, with the meniscus found to be stiffest in deionised water (E = 1.15 MPa) and least stiff in 3M PBS (E = 0.43 MPa), with the value of E in 0.14M PBS falling in between (0.68 MPa). No differences were observed in the zero strain permeability or the exponential strain dependent/stiffening coefficients. The viscoelastic coefficient and relaxation time values were not found to improve model fit and were thus held at zero. The mean R2 value was 0.78, indicating a good fit and did not differ significantly between solutions. Proteoglycan content was not found to differ with solution, but was found to be significantly increased in the middle region of both menisci. Proteoglycans make a significant electrostatic contribution to mechanical stiffness of the meniscus, increasing it by 58% in the physiological condition, and are hence integral to its function. It is important to include the influence of ionic effects when modelling meniscus, particularly where fluid flow or localised strain is modelled. From a clinical perspective, it is critical that meniscal regeneration strategies such as scaffolds or allografts attempt to preserve, or compensate for, the function of proteoglycans to ensure normal meniscal function

Rotator cuff repair is performed to treat shoulder pain and disability. Failure of the tendon repair site is common; one strategy to improve healing is to enforce a period of post-operative immobilisation. Immobilisation may have unintended effects on tendon healing. Tenocytes under uniaxial strain form more organised collagen and up regulate expression of proliferative genes. Vitamin C (ascorbic acid), an anti-oxidant that is a co-factor for collagen synthesis, has also been reported to enhance collagen deposition and organisation. The purpose of this study was to compare human tenocyte cultures exposed to uniaxial cyclical strain with or without slow-release ascorbic acid (ascorbyl-2 phosphate) to determine their individual and combined effects on tissue remodelling and expression of tissue repair genes. Rotator cuff tissues were collected from degenerative supraspinatus tears from eight patients. Tenocytes were incorporated into 3D type I collagen culture matrices. Cultures were divided into four groups: 1) ascorbic acid (0.6mMol/L) + strain (1%–20% uniaxial cyclic strain at 0.1 Hz), 2) ascorbic acid unstrained, 3) strain + vehicle 4) unstrained + vehicle. Samples were fixed in paraffin, stained with picrosirius red and analysed with circular polarising light. A second set of cultures were divided into three groups: 1) 0.5mM ascorbic acid, 2) 1mM ascorbic acid, 3) vehicle cultured for 24, 72, 120 and 168 hours. Cell-free collagen matrix was used as a control. Tenocyte proliferation was assessed using the water soluble tetrazolium-1 (WST1) assay and f tissue repair gene expression (TGFB1, COL1A1, FN1, COLIII, IGF2, MMP1, and MMP13), were analysed by qPCR. The data were analysed using a Split model ANOVA with contrast and bonferroni correction and a one-way ANOVAs and Tukey's test (p<0.05 was significant). Our results indicated that unstrained cultures with or without exposure to slow release ascorbic acid exhibited greater picrosirius red birifringency and an increase in collagen fiber deposition in a longitudinal orientation compared to strained tenocytes. We found that slow release ascorbic acid promoted significant dose and culture-time dependent increases in tenocyte proliferation (p<0.05) but no obvious enhancement in collagen deposition was evident over cultures without ascorbic acid supplementation. Based on these data, applying strain to tenocytes may result in less organised formation of collagen fibers, suggestive of fibrotic tissue, rather than tendon remodelling. This may indicate that a short period of immobilisation post-rotator cuff repair is beneficial for the healing of tendons. Exposure to slow release ascorbic acid enhanced tenocyte proliferation, suggesting that supplementation with Vitamin C may improve tendon repair post-injury or repair. Future studies will assess levels of tissue repair-associated proteins as well as comparing traumatic and degenerative rotator cuff tears to healthy uninjured rotator cuff tissue

Cortical bone is a complex composite material composed of an inorganic mineral phase and organic matrix of type I collagen and various non-collagenous proteins. The hierarchical organisation of bone results in a transversely isotropic material with the mechanical properties in the long-axis (z) being superior to the radial and circumferential axes which are equivalent. This directional dependence of bone has been well reported, whilst the mechanisms/anisotropy are more difficult to study. This study examined the anistropic nature of cortical bone and the influence of different sterilisation procedures. Ninety cortical bone cubes were prepared using established techniques (Walsh and Guzelsu) and randomly allocated to three treatments; control, 15 KGy, Super Critical Fluid (SCF) (n=30 per group). The ultrasonic moduli was examined using longitudinal sound waves at 5 MHz using a pulse receive technique. Unconfined compression was performed non-destructively in longitudinal (z), circumferential (ï±) and radial orientations (r). Samples were tested to failure in the z axis. A two-way analysis of variance (treatment and time) followed by a Games Howell post hoc test and covariate analysis was performed using SPSS for Windows. Data from this study revealed some interesting and intriguing results with respect to the effects of gamma irradiation and dense gas technology on the properties of cortical bone and load transmission. A statistical decrease in the compressive stiffness and strength was noted with 15 KGy of whilst SCF treatment did not alter the properties in the r or ï orientations. Similar results were found with respect to the ultrasonic moduli (data not shown). The pilot data confirmed the adverse effects of bone in compression following gamma irradiation as we found in our recently presented ORS work. However, the study in compression demonstrated that the directional dependence that makes cortical bone a transversely isotropic material is removed following gamma irradiation with SCF did not appear to have this effect. The effects of gamma irradiation on the mechanical performance of allografts in the long bone axis may play a role in their in vivo performance. The removal of the anisotropy following gamma irradiation provides insight into the relationship(s) between the mineral and organic constituents, which requires further study

Purpose. The biomechanical role of the meniscus in the knee joint is a function of its extracellular matrix which consists of type I collagen throughout, type II collagen in the inner meniscus region and glycosaminoglynated (GAG) proteins of which aggrecan is the most prevaleet. Meniscus reparative capacity is limited, particularly when a defect is located in the inner avascular portion, and menisectomy predisposes the joint to osteoarthritis. Using meniscus cells in tissue engineering strategies has been advocated to generate functional meniscus substitutes. However, meniscus cells, like chondrocytes of cartilage, lose their matrix-forming phenotype during culture expansion. Co-culture of chondrocytes with stem cells has been shown to result in enhanced matrix formation. We hypothesized that meniscus cells in co-culture with stem cells will result in increased matrix formation. Method. Tissue specimens were obtained after approval of the local ethical committee and informed consent. Menisci were obtained from 3 patients undergoing total knee arthroplasty; (53–84; mean age 66.6). Meniscus cells were isolated after digestion of menisci with collagenase II. Isolated meniscus cells were plated for 24–48 hr before use. Bone marrow aspirates were obtained from the iliac crest of 3 donors: 1 female (46) and 2 males (15 and 21) undergoing routine orthopaedic procedures. Plastic adherent bone marrow stromal cell populations were isolated and expanded under normal oxygen tension of 21%O2 in a-MEM growth media plus FGF-2 until passage 2. Cells were mixed at a variety of meniscus cells (Men): BMSC ratio including 5/95, 10/90 and 25/75, respectively. Mixed cells were centrifuged to form spherical pellets followed by culture in a defined serum free chondrogenic differentiation medium. Control groups were pure Men and pure BMSCs. Total cell number per pellet was 25×104. Pellets were cultured for 3 weeks under normal oxygen tension. Thereafter, pellets were processed: biochemically for GAG and DNA content, and histologically for Safranin-O staining of sulphated GAG and immunohistochemical analyses for collagen types I and II. Analysis was performed on a minimum of 2 independent pellets. Results. Relative to pure cell control pellets, co-cultured cell pellets of expanded human BMSCs and meniscus cells had more GAG matrix per DNA content. The amplitude of GAG enhancement in all co-cultures varied with donor and with the Men:BMSC ratio. However, the mean GAG enhancement was 1.8–6 fold. The GAG contents of pellets correlated with Safranin-O staining. Positive staining for collagens types I and II was increased in co-cultured cell pellets. Conclusion. Co-seeding of meniscus cells and stem cells on a suitable scaffold may aid the generation of functional grafts with improved biomechanical properties relative to those generated via expanded meniscus cells alone or stem cells alone

Purpose. A major drawback of current cartilage and intervertebral disc (IVD) tissue engineering is that human mesenchymal stem cells (MSCs) from osteoarthritic (OA) patients express high levels of type X collagen. Type X collagen is a marker of late stage chondrocyte hypertrophy, linked with endochondral ossification, which precedes bone formation. However, it has been shown that a novel plasma-polymer, called nitrogen-rich plasma-polymerized ethylene (PPE:N), is able to inhibit type X collagen expression in committed MSCs. The aim of this study was to determine if the decreased expression of type X collagen, induced by the PPE:N surfaces is maintained when MSCs are removed from the surface and transferred to pellet cultures in the presence of serum and growth factor free chondrogenic media. Method. Human MSCs were obtained from aspirates from the intramedullary canal of donors undergoing total hip replacement for OA. Cells were expanded for 2–3 passages and then cultured on polystyrene dishes and on two different PPE:N surfaces: high (H) and low (L) pressure deposition. Cells were transferred for 7 additional days in chondrogenic serum free media (DMEM high glucose supplemented with 2 mM L-glutamine, 20 mM HEPES, 45 mM NaHCO3, 100 U/ml penicillin, 100 ug/ml streptomycin, 1 mg/ml bovine serum albumin, 5 ug/ml insulin, 50 ug/ml ascorbic acid, 5 ng/ml sodium selenite, 5 ug/ml transferrin) in pellet culture or on PS cell culture dishes. RNA was extracted using a standard TRIzol protocol. RT-PCR was realized using Superscript II (RT) and Taq polymerase (PCR) with primers specific for type I and X collagen. GAPDH was used as a housekeeping gene and served to normalize the results. Results. As observed in previous studies, type X collagen mRNA level was suppressed when cultured on both H- and L-PPE:N. HPPE:N was more effective in decreasing type X collagen expression than LPPE:N (55 vs. 78 % of control OA cells). Results also showed that the decreased type X collagen mRNA level was maintained not only when cells were removed from the PPE:N surfaces and transferred to new polystyrene culture dishes in the presence of chondrogenic media, but also when transferred to pellet cultures. Culturing MSCs from OA patients on PPE:N surfaces and in pellet culture had however no effect on the level of type I collagen mRNA. Conclusion. The present study confirmed the potential of PPE:N surfaces in suppressing type X collagen expression in MSCs from OA patients. More importantly, when these cells are transferred to pellet cultures, type X collagen suppression is maintained. These results may lead us one step closer to the production of large amounts of reprogrammed MSCs for tissue engineering applications

The bioactive polyetheretherketone (PEEK) was fabricated by the combination of PEEK and CaO-SiO. 2. particles, which formed hydroxyapatite on its surfaces in simulated body fluid and showed good mechanical propeties. The study revealed osteoblast-like cell proliferation and gene expression on the bioactive PEEK. Materials and Methods. Peek and bioactive PEEK discs (24 mm in diameter and 2 mm in thickness) were prepared. Bioactive PEEk was produced by the combination of 80 vol% Peek powder and 20 vol% CaO-SiO. 2. particles (30CaO · 70SiO. 2. ). Discs were sterilized with ethylene oxide gas. The study was approved by the ethics committee in Chiba University. Human osteoblast-like cells were used in the study. The cells at passage 3–5 were used in the experiments. 2 × 10. 5. cells /disc were culture at 37°C in a humidified atmosphere with 5% CO. 2. , and the media was replaced every 3 days. At days 3, 7, 21, the culture media, cells and discs were collected respectively. Cell attachment assay was performed. Cells were seeded at a density of 4 × 10. 5. cells /well and incubated for 2 hours at 37 C in a humidified atmosphere with 5% CO. 2. The cells on the discs were evaluated by DNA content. The real-time PCR was performed with regard to type I collagen (COLI), osteocalcin (OC), osteonectin (ON), osteopontin (OPN), and GAPDH. The alkaline phosphatase activity (ALP) was measeured at 3, 7, and 21 days, which samples as used in the DNA-content assay. Alizalin Red Staining was performed at day 21 to quantify calcification deposits in discs. Results were analyzed using Student's t-test with at least three samples. The level of siginificance was set at p=0.05. Results. The content of DNA showed similar increases on PEEK and bioactive PEEK in the course of day 3, 7, 21. The cell attachment of bioactive PEEK was two times larger than that of PEEK. Real-time PCR results of human osteoblast-like cells cultured on PEEK and bioactive PEEK discs were shown in Fig. 1. There were no significant differences between cells on PEEK and bioactive PEEK with respect to COL I and ON mRNA expression. However, human osteoblast-like cells on bioactive PEEK presented higher expression of OPN and OCN mRNA at day 21. No significant differences were found in ALP activity of both discs. Calcification deposits were observed only on bioactive PEEK at day 21. Discussion. The bioactive PEEK, with the combination of 80 vol% Peek powder and 20 vol% CaO-SiO. 2. particles (30CaO · 70SiO. 2. ) showed 123.5 MPa and 6.43 GPa in bending strength and Young's modulus, respectively. The bioactive PEEK has the aggregated CaO-SiO. 2. oarticles between the PEEK particles on its surface, which causes hydroxyapatite formation in vivo. The mechanism is considered to enhance the osteoblast attachment ability, and induce OPN and OC mRNA expression, following the calcification of human osteobloast-like cells. Therefore, the study indicated that bioactive PEEK is the most promising for use as an orthopedic implant

Aims

The timing of when to remove a circular frame is crucial; early removal results in refracture or deformity, while late removal increases the patient morbidity and delay in return to work. This study was designed to assess the effectiveness of a staged reloading protocol. We report the incidence of mechanical failure following both single-stage and two stage reloading protocols and analyze the associated risk factors.

Autologous chondrocyte implantation is now a recognised treatment for patients with knee pain secondary to articular cartilage defects. The initial technique involving periosteum as the cover for the implanted cells (ACI-P) has been modified to the use of a type I/III collagen membrane (ACI-C). Matrix-induced Autologous Chondrocyte Implantation (MACI) is a technique in which autologous donor chondrocytes are implanted onto the collagen membrane and then fixed into the defect with fibrin glue. We performed a prospective randomised comparison of 247 patients (126 ACI and 121 MACI). Patients' pain and function were assessed with mean follow-up of 42 months. Function was measured using the Modified Cincinnati and Stanmore Scoring systems. Arthroscopic assessment was by the ICRS classification. The influence of the size and site of the lesion, sex, age and previous knee surgery on the results was analysed. The Modified Cincinnati score showed a mean 17.5 point rise from pre-operative scores in the ACI group and 19.6 point rise in the MACI group. Pain, measured using the Visual Analogue Score, showed an improvement in both arms of the trial. Both chondrocyte implantation methods showed improvement in 86% of patients clinically and arthroscopically, with excellent and good results in 50% and fair results in 30% of patients. 20% of patients showed no improvement in function but none were worse. There were no serious complications. Limited histological analysis showed hyaline cartilage in a higher but non-significant proportion of ACI-C cases. With over 11 years' experience in the use of both forms of cartilage implantation we have established more precisely the indications for chondrocyte implantation. Although MACI is technically a more attractive option in most cases, because of ease and speed of the procedure, longer term follow-up is required to assess the longevity of ACI-C and MACI and the effect on prevention of ‘early-onset’ Osteoarthritis

Nanotechnology is the study, production and controlled manipulation of materials with a grain size < 100 nm. At this level, the laws of classical mechanics fall away and those of quantum mechanics take over, resulting in unique behaviour of matter in terms of melting point, conductivity and reactivity. Additionally, and likely more significant, as grain size decreases, the ratio of surface area to volume drastically increases, allowing for greater interaction between implants and the surrounding cellular environment. This favourable increase in surface area plays an important role in mesenchymal cell differentiation and ultimately bone–implant interactions.

Basic science and translational research have revealed important potential applications for nanotechnology in orthopaedic surgery, particularly with regard to improving the interaction between implants and host bone. Nanophase materials more closely match the architecture of native trabecular bone, thereby greatly improving the osseo-integration of orthopaedic implants. Nanophase-coated prostheses can also reduce bacterial adhesion more than conventionally surfaced prostheses. Nanophase selenium has shown great promise when used for tumour reconstructions, as has nanophase silver in the management of traumatic wounds. Nanophase silver may significantly improve healing of peripheral nerve injuries, and nanophase gold has powerful anti-inflammatory effects on tendon inflammation.

Considerable advances must be made in our understanding of the potential health risks of production, implantation and wear patterns of nanophase devices before they are approved for clinical use. Their potential, however, is considerable, and is likely to benefit us all in the future.

Cite this article: Bone Joint J 2014; 96-B: 569–73.

The ability of mesenchymal stem cells (MSCs) to differentiate in vitro into chondrocytes, osteocytes and myocytes holds great promise for tissue engineering. Skeletal defects are emerging as key targets for treatment using MSCs due to the high responsiveness of bone to interventions in animal models. Interest in MSCs has further expanded in recognition of their ability to release growth factors and to adjust immune responses.

Despite their increasing application in clinical trials, the origin and role of MSCs in the development, repair and regeneration of organs have remained unclear. Until recently, MSCs could only be isolated in a process that requires culture in a laboratory; these cells were being used for tissue engineering without understanding their native location and function. MSCs isolated in this indirect way have been used in clinical trials and remain the reference standard cellular substrate for musculoskeletal engineering. The therapeutic use of autologous MSCs is currently limited by the need for ex vivo expansion and by heterogeneity within MSC preparations. The recent discovery that the walls of blood vessels harbour native precursors of MSCs has led to their prospective identification and isolation. MSCs may therefore now be purified from dispensable tissues such as lipo-aspirate and returned for clinical use in sufficient quantity, negating the requirement for ex vivo expansion and a second surgical procedure.

In this annotation we provide an update on the recent developments in the understanding of the identity of MSCs within tissues and outline how this may affect their use in orthopaedic surgery in the future.

Cite this article: Bone Joint J 2014;96-B:291–8.

Peri-prosthetic osteolysis and subsequent aseptic loosening is the most common reason for revising total hip replacements. Wear particles originating from the prosthetic components interact with multiple cell types in the peri-prosthetic region resulting in an inflammatory process that ultimately leads to peri-prosthetic bone loss. These cells include macrophages, osteoclasts, osteoblasts and fibroblasts. The majority of research in peri-prosthetic osteolysis has concentrated on the role played by osteoclasts and macrophages. The purpose of this review is to assess the role of the osteoblast in peri-prosthetic osteolysis.

In peri-prosthetic osteolysis, wear particles may affect osteoblasts and contribute to the osteolytic process by two mechanisms. First, particles and metallic ions have been shown to inhibit the osteoblast in terms of its ability to secrete mineralised bone matrix, by reducing calcium deposition, alkaline phosphatase activity and its ability to proliferate. Secondly, particles and metallic ions have been shown to stimulate osteoblasts to produce pro inflammatory mediators in vitro. In vivo, these mediators have the potential to attract pro-inflammatory cells to the peri-prosthetic area and stimulate osteoclasts to absorb bone. Further research is needed to fully define the role of the osteoblast in peri-prosthetic osteolysis and to explore its potential role as a therapeutic target in this condition.

Cite this article: Bone Joint J 2013;95-B:1021–5.