Revolving doors of tendinopathy: definition, pathogenesis and treatment.

The ultimate cure for the tendon pathology continues to elude current science. Despite great steps in technology, the causation and treatment is still not clear. The number of different theories and treatment modalities in the literature may confuse clinicians and patients. In this paper we outline the definitions, evolution of pathogenesis and treatment for tendinopathy. By highlighting these, the aim of this paper is to guide the practitioner in counselling and treating their patients.

Correction to: The effect of cationically-modified phosphorylcholine polymers on human osteoblasts in vitro and their effect on bone formation in vivo.

The article "The effect of cationically modified phosphorylcholine polymers on human osteoblasts in vitro and their effect on bone formation in vivo", written by Jonathan M. Lawton, Mariam Habib, Bingkui Ma, Roger A. Brooks, Serena M. Best, Andrew L. Lewis, Neil Rushton and William Bonfield, was originally published Online First without open access. After publication in volume 28, issue 9, page 144 it was noticed that the copyright was wrong in the PDF version of the article. The copyright of the article should read as "

The effect of cationically-modified phosphorylcholine polymers on human osteoblasts in vitro and their effect on bone formation in vivo.

The effect of introducing cationic charge into phosphorylcholine (PC)-based polymers has been investigated in this study with a view to using these materials as coatings to improve bone formation and osseointegration at the bone-implant interface. PC-based polymers, which have been used in a variety of medical devices to improve biocompatibility, are associated with low protein adsorption resulting in reduced complement activation, inflammatory response and cell adhesion. However, in some applications, such as orthopaedics, good integration between the implant and bone is needed to allow the distribution of loading stresses and a bioactive response is required. It has previously been shown that the incorporation of cationic charge into PC-based polymers may increase protein adsorption that stimulates subsequent cell adhesion. In this paper, the effect of cationic charge in PC-based polymers on human osteoblasts (HObs) in vitro and the effect of these polymers on bone formation in the rat tibia was assessed. Increasing PC positive surface charge increased HOb cell adhesion and stimulated increased cell differentiation and the production of calcium phosphate deposits. However, when implanted in bone these materials were at best biotolerant, stimulating the production of fibrous tissue and areas of loosely associated matrix (LAM) around the implant. Their development, as formulated in this study, as bone interfacing implant coatings is therefore not warranted.

Bioactive IGF-1 release from collagen-GAG scaffold to enhance cartilage repair in vitro.

Tissue engineering is a promising technique for cartilage repair. Toward this goal, a porous collagen-glycosaminoglycan (CG) scaffold was loaded with different concentrations of insulin-like growth factor-1 (IGF-1) and evaluated as a growth factor delivery device. The biological response was assessed by monitoring the amount of type II collagen and proteoglycan synthesised by the chondrocytes seeded within the scaffolds. IGF-1 release was dependent on the IGF-1 loading concentration used to adsorb IGF-1 onto the CG scaffolds and the amount of IGF-1 released into the media was highest at day 4. This initial IGF-1 release could be modelled using linear regression analysis. Osteoarthritic (OA) chondrocytes seeded within scaffolds containing adsorbed IGF-1 deposited decorin and type II collagen in a dose dependent manner and the highest type II collagen deposition was achieved via loading the scaffold with 50 µg/ml IGF-1. Cells seeded within the IGF-1 loaded scaffolds also deposited more extracellular matrix than the no growth factor control group thus the IGF-1 released from the scaffold remained bioactive and exerted an anabolic effect on OA chondrocytes. The effectiveness of adsorbing IGF-1 onto the scaffold may be due to protection of the molecule from proteolytic digestion allowing a more sustained release of IGF-1 over time compared to adding multiple doses of exogenous growth factor. Incorporating IGF-1 into the CG scaffold provided an initial therapeutic burst release of IGF-1 which is beneficial in initiating ECM deposition and repair in this in vitro model and shows potential for developing this delivery device in vivo.

Immobilized MWCNT support osteogenic cell culture.

The broad use of versatile, strong, lightweight multi-walled carbon nanotubes (MWCNT) for use in biomaterial applications is tempered by ongoing debate about their safety. Recent reports suggest that factors such as their diameter and surface coating affect their function and cytotoxicity. The cell culture surfaces used in the current study were made of MWCNT immobilized in a high-density polyethylene substrate, differentiating it from most studies of MWCNT cytotoxicity. The purity, chemical functionalization, and immobilization of MWCNT were evaluated to elucidate their effect on MWCNT behavior relative to controls. While purity was found not to be significant in determining the behavior of cells on MWCNT relative to standard controls, the presence of carboxyl functional groups was generally associated with reduced cell metabolic activity, proliferation, and differentiation as measured using the MTS assay, nucleic acid incorporation, and alkaline phosphatase expression, respectively. This study demonstrates that the culture of osteogenic cells on surfaces made of nonfunctionalized and immobilized MWCNT is associated with a level of cell growth and differentiation comparable to those of standard tissue culture controls.

The effect of platelet-rich plasma on clinical outcomes in lateral epicondylitis.

PURPOSE: To evaluate the evidence for application of platelet-rich plasma (PRP) in lateral epicondylitis. METHODS: We carried out a systematic review of the current evidence on the effects of PRP in lateral epicondylitis on clinical outcomes. We performed a comprehensive search of the PubMed, Medline, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Embase databases using various combinations of the commercial names of each PRP preparation and "lateral epicondylitis" (with its associated terms), looking specifically at human studies. Data validity was assessed and collected on clinical outcome. RESULTS: Nine studies met the inclusion criteria, of which 5 were randomized controlled trials. Two cohort studies showed that PRP improved clinical satisfaction scores. One case-control study showed that PRP yielded a significantly greater improvement in symptoms compared with bupivacaine. Two randomized controlled trials compared the effect of injections of PRP and blood. Only 1 of the studies noted a significant difference at the 6-week time point. Three randomized controlled trials compared corticosteroids with PRP. Two of the smaller trials, which had follow-up periods of 6 weeks and 3 months, showed no significant difference between treatment groups. The largest randomized controlled trial found that PRP had significant benefit compared with corticosteroids with regard to pain and Disabilities of the Arm, Shoulder and Hand scores at 1- and 2-year time points. CONCLUSIONS: This review highlights the limited but evolving evidence for the use of PRP in lateral epicondylitis; however, further research is required to understand the concentration and preparation that facilitate the best clinical outcome. Characterizing the timing of the intervention would optimize the health economics behind the decision to treat for the patient and health care provider. LEVEL OF EVIDENCE: Level III, systematic review of Level I to III studies.

Collagen fibre implant for tendon and ligament biological augmentation. In vivo study in an ovine model.

PURPOSE: Although most in vitro studies indicate that collagen is a suitable biomaterial for tendon and ligament tissue engineering, in vivo studies of implanted collagen for regeneration of these tissues are still lacking. The objectives of this study were the following: (1) to investigate the regeneration of the central third of the ovine patellar tendon using implants made of an open array of collagen fibres (reconstituted, extruded bovine collagen); and (2) to compare two collagen crosslinking chemistries: carbodiimide and carbodiimide associated with ethyleneglycoldiglycidylether. METHODS: Forty-eight Welsh Mountain sheep were operated on their right hind leg. The central third of patellar tendon was removed and substituted with carbodiimide (n = 16) and carbodiimide-ethyleneglycoldiglycidylether-crosslinked implants (n = 16). In the control group the defect was left empty (n = 16). The central third of contralateral unoperated tendons was used as positive controls. Half of the sheep in each group were killed at 3- and 6-month time points. After proper dissection, tendon sub-units (medial, central and lateral) were tested to failure (n = 6 for each group), whilst 2 non-dissected samples were used for histology. RESULTS: Both the implants had significantly lower stress to failure and modulus with respect to native tendon at both 3- and at 6-month time points. The implants did not statistically differ in stress to failure, whilst carbodiimide-crosslinked implants had significantly higher modulus than carbodiimide-ethyleneglycoldiglycidylether-crosslinked implants both at 3 and at 6 months. Histology showed carbodiimide-crosslinked implants to have a better integration with the native tendon than carbodiimide-ethyleneglycoldiglycidylether-crosslinked implants. Carbodiimide-crosslinked implants appeared partially resorbed and showed increased tissue ingrowth with respect to carbodiimide-ethyleneglycoldiglycidylether-crosslinked implants. CONCLUSIONS: To deliver collagen implants as an open array of fibres allows optimal tendon-implant integration and good ingrowth of regenerated tissue. In the present study the resorption rate of both the examined implants was too low due to the high level of crosslinking. This led to only minor substitution of the implant with regenerated tissue, which in turn produced a low-strength implanted region. Further studies are needed to find the right balance between strength and resorption rate of collagen fibres.

Exploring the application of stem cells in tendon repair and regeneration.

PURPOSE: To conduct a systematic review of the current evidence for the effects of stem cells on tendon healing in preclinical studies and human studies. METHODS: A systematic search of the PubMed, CINAHL (Cumulative Index to Nursing and Allied Health Literature), Cochrane, and Embase databases was performed for stem cells and tendons with their associated terminology. Data validity was assessed, and data were collected on the outcomes of trials. RESULTS: A total of 27 preclinical studies and 5 clinical studies met the inclusion criteria. Preclinical studies have shown that stem cells are able to survive and differentiate into tendon cells when placed into a new tendon environment, leading to regeneration and biomechanical benefit to the tendon. Studies have been reported showing that stem cell therapy can be enhanced by molecular signaling adjunct, mechanical stimulation of cells, and the use of augmentation delivery devices. Studies have also shown alternatives to the standard method of bone marrow-derived mesenchymal stem cell therapy. Of the 5 human studies, only 1 was a randomized controlled trial, which showed that skin-derived tendon cells had a greater clinical benefit than autologous plasma. One cohort study showed the benefit of stem cells in rotator cuff tears and another in lateral epicondylitis. Two of the human studies showed how stem cells were successfully extracted from the humerus and, when tagged with insulin, became tendon cells. CONCLUSIONS: The current evidence shows that stem cells can have a positive effect on tendon healing. This is most likely because stem cells have regeneration potential, producing tissue that is similar to the preinjury state, but the results can be variable. The use of adjuncts such as molecular signaling, mechanical stimulation, and augmentation devices can potentially enhance stem cell therapy. Initial clinical trials are promising, with adjuncts for stem cell therapy in development.

Platelet-Rich Plasma Augmentation of Arthroscopic Rotator Cuff Repair Lowers Retear Rates and Improves Short-Term Postoperative Functional Outcome Scores: A Systematic Review of Meta-Analyses.

Purpose: The purpose of this study is to conduct a systematic review of meta-analyses of rotator cuff repair using platelet-rich plasma (PRP) to identify whether PRP improves clinical function and rate of tendon retears. We will (1) conduct a systematic review of the current meta-analyses of rotator cuff repair using platelet-rich plasma available in the literature, (2) evaluate the quality of these meta-analyses using the Preferred Reporting Items for Systematic Review (PRISMA) methodology, (3) identify whether PRP improves clinical function and rate of tendon retears, and develop guidance to improve future studies in this area. Methods: We carried out a systematic review of previous meta-analyses published on the clinical outcomes of PRP used in the treatment of rotator cuff tears. We performed a comprehensive search of PubMed, Medline, Cochrane, CINAHL (Cumulative Index to Nursing and Allied Health Literature), and Embase databases, using various combinations of the commercial names of each PRP preparation and "rotator cuff" (with its associated terms), looking specifically at human meta-analysis studies involving the repair of the rotator cuff tendon surgically in the English language. Data validity was assessed and collected on clinical outcomes. Following this, a meta-analysis was undertaken. Results: Thirteen meta-analyses met the inclusion and exclusion criteria. All were considered of similar quality with Oxman-Guyatt index of 9 and PRISMA score of more than 24. A total of 1,800 patients with an average follow up of 12 to 36 months. The use of PRP for arthroscopic rotator cuff tear, when compared with controls, leads to a lower number of retears, improved short-term postoperative scores, and functional outcome. The following postoperative scores were reported: Constant: 12, Simple Shoulder Test: 10, ASES (American Shoulder and Elbow Surgeons): 9, UCLA (University of California, Los Angeles) 11, SANE (Single Assessment Numeric Evaluation) 1, VAS (visual analog scale): 6, and Retears: 13. Subgroup analysis showed that leukocyte content and gel application make no difference in the effectiveness of PRP. VAS score subgroup analysis showed short-term pain relief. Conclusions: Our study shows that PRP is effective in reducing retears after rotator cuff repair and improving functional outcome scores and reducing short-term pain. Level of Evidence: Level III, systematic review of Level I-III studies.

Extruded collagen fibres for tissue engineering applications: effect of crosslinking method on mechanical and biological properties.

Reconstituted collagen fibres are promising candidates for tendon and ligament tissue regeneration. The crosslinking procedure determines the fibres' mechanical properties, degradation rate, and cell-fibre interactions. We aimed to compare mechanical and biological properties of collagen fibres resulting from two different types of crosslinking chemistry based on 1-ethyl-3-(3-dimethyllaminopropyl)carbodiimide (EDC). Fibres were crosslinked with either EDC or with EDC and ethylene-glycol-diglycidyl-ether (EDC/EGDE). Single fibres were mechanically tested to failure and bundles of fibres were seeded with tendon fibroblasts (TFs) and cell attachment and proliferation were determined over 14 days in culture. Collagen type I and tenascin-C production were assessed by immunohistochemistry and dot-blotting. EDC chemistry resulted in fibres with average mechanical properties but the highest cell proliferation rate and matrix protein production. EDC/EGDE chemistry resulted in fibres with improved mechanical properties but with a lower biocompatibility profile. Both chemistries may provide useful structures for scaffolding regeneration of tendon and ligament tissue and will be evaluated for in vivo tendon regeneration in future experiments.

Platelet-rich plasma activation in combination with biphasic osteochondral scaffolds-conditions for maximal growth factor production.

PURPOSE: The combination of scaffolds and biological factors may enhance articular cartilage repair. Little is known regarding the activation and subsequent growth factor release of platelet-rich plasma (PRP) in contact with biosynthetic scaffolds. The purpose of this study was i) to identify whether the addition of thrombin was required to activate PRP in the presence of a collagen osteochondral scaffold and ii) to compare the activity of PRP when applied to both collagen- and polylactide-based osteochondral scaffolds. METHODS: Equal combined volumes of test substances were used (n = 3): 500 µl PRP alone or on scaffolds; 375 µl PRP + 125 µl autologous thrombin on scaffolds; 455 µl PRP + 45 µl bovine thrombin on scaffolds. Scaffolds and/or PRP were cultured in vitro in DMEM/F12 medium for 10 days. TGF-ß1, PDGF-AB and bFGF were measured using ELISA. RESULTS: A similar cumulative release profile in all growth factors was found over the 10-day period i.e. a burst release and further physiological prolonged release. A significantly higher release of PDGF-AB was seen in the PRP + collagen scaffold groups at all time points, compared to scaffold + PRP + thrombins (P < 0.001). A significantly increased cumulative volume of PDGF-AB was released from the collagen scaffold compared to the polylactide scaffold (P < 0.001). CONCLUSION: This study shows that polylactide and particularly collagen osteochondral scaffolds activate PRP in vitro. If PRP is combined with these scaffolds clinically, no exogenous activation with thrombin is required to achieve growth factor release, which may be of benefit for articular cartilage repair applications.

Direct inhibition of osteoclast formation and activity by the vitamin E isomer gamma-tocotrienol.

Vitamin E homologues, specifically tocotrienols, have been shown to have favorable effects on bone. They possess properties that are indicative of anti-resorptive activity, suggesting the potential for vitamin E in preventing bone loss. To investigate the anti-resorptive activity of the various vitamin E homologues, we cultured human osteoclasts from blood-derived CD14+ cells on collagen, dentin, and calcium phosphate substrates, with some samples supplemented with vitamin E homologues in their cell culture medium. These were compared to the clinically used bisphosphonate, pamidronate. Compounds were either added at the start of culture to study effects on osteoclast formation, or at the start of osteoclastic resorption to determine their effects on activity. The alpha- and gamma-tocotrienol isomers inhibited osteoclast formation without consequent reduction in total cell number. Only gamma-tocotrienol inhibited osteoclast activity without toxicity. Gamma-tocotrienol was the most potent inhibitor of both osteoclast formation and activity and requires further investigation into its anti-resorptive effects on bone.

Human osteoblasts obtained from distinct periarticular sites demonstrate differences in biological function in vitro.

AIMS: Accumulated evidence indicates that local cell origins may ingrain differences in the phenotypic activity of human osteoblasts. We hypothesized that these differences may also exist in osteoblasts harvested from the same bone type at periarticular sites, including those adjacent to the fixation sites for total joint implant components. METHODS: Human osteoblasts were obtained from the acetabulum and femoral neck of seven patients undergoing total hip arthroplasty (THA) and from the femoral and tibial cuts of six patients undergoing total knee arthroplasty (TKA). Osteoblasts were extracted from the usually discarded bone via enzyme digestion, characterized by flow cytometry, and cultured to passage three before measurement of metabolic activity, collagen production, alkaline phosphatase (ALP) expression, and mineralization. RESULTS: Osteoblasts from the acetabulum showed lower proliferation (p = 0.034), cumulative collagen release (p < 0.001), and ALP expression (p = 0.009), and produced less mineral (p = 0.006) than those from the femoral neck. Osteoblasts from the tibia produced significantly less collagen (p = 0.021) and showed lower ALP expression than those from the distal femur. CONCLUSION: We have demonstrated for the first time an anatomical regional variation in the biological behaviours of osteoblasts on either side of the hip and knee joint. The lower osteoblast proliferation, matrix production, and mineralization from the acetabulum compared to those from the proximal femur may be reflected in differences in bone formation and implant fixation at these sites. Cite this article: Bone Joint Res 2021;10(9):611-618.

Holding on by a thread: the continuing story of rotator cuff tears.

Rotator cuff tears are a common cause of shoulder pain. The incidence of these tears has increased significantly over the years, with the demands of an increasingly active elderly population. Therefore, a detailed understanding of rotator cuff tears will help doctors manage their patients' condition. This field has rapidly advanced over the past decade and this review provided an insight into the latest developments.

Production and characterization of HA and SiHA coatings.

Plasma sprayed hydroxyapatite (HA) coatings on metallic prostheses have been used clinically in dentistry and orthopedics since the mid 1980s. The coating properties are dependent on the spraying parameters. Since silicon-substituted hydroxyapatite (SiHA) has been shown to offer improved bioactivity over phase pure HA, SiHA coatings have the potential for enhanced performance in clinical application. In this study, phase pure HA and 0.8 wt% SiHA powders were synthesized with similar particle size distribution and morphology. The powders were plasma sprayed onto Ti-6Al-4V substrates at 37 kW and 40 kW plasma gun input power respectively. Four kinds of samples were prepared, HAC 37, HAC 40, SiHAC 37 and SiHAC 40. Materials characterization showed that the coatings were of relatively high phase purity. In vitro cell culture demonstrated that human osteoblast cells grew well on all samples, with the highest cell growth observed on SiHA coatings produced under the lower plasma gun input power.

Tissue Engineering for the Ovine Rotator Cuff: Surgical Anatomy, Approach, Implantation and Histology Technique, along with Review of Literature.

Aim: Tissue engineering is a contemporary topic, which is widely discussed in shoulder surgery. The preclinical success of tissue engineering has not yet fully translated to clinical studies. In this study, we present our experience in this subject and discuss measurements to analyze the sheep tissue as comparative model. We also present a comprehensive systematic review of the literature in relation to tissue engineering and rotator cuff. Method: We studied the anatomy, histology and surgical approach of 24 infraspinatus tendons specimens in sheep and focused on certain measurements such as: (1) size of the normal tendon; (2) diameter of the normal footprint; and (3) bone hardness of the footprint using a durometer. Blood from six sheep was obtained and processed to produce platelet rich plasma using both the Harvest Smartprep and Cascade kit. We then outlined an approach to the infraspinatus tendon footprint in preparation for implantation of a biological augmentation material, which was repaired using a double row technique. This was followed by a histological analysis. Results: The average measurements of the footprint were 21 mm ×21 mm, the tendon length was 35.1 mm and the width proximal and distal was 21.9 and 14 mm, respectively. The average bone hardness at the 12, 3, 6, and 9 o'clock position was 64.1, 52.3, 50.1, and 37.7 respectively. Central footprint and lateral edge hardness was 44.8 and 43.4. Only the Harvest Smartprep and using a modified method, was able to produce a platelet concentration factor of 4. The Cascade method was unable to concentrate sheep blood. Conclusion: The sheep model is a suitable tissue for studying the rotator cuff. The researcher must be aware of certain interspecies caveats. Clinical tissue engineering and surgical techniques must be modified in order to be suitable when using sheep model.

The role of electrosprayed apatite nanocrystals in guiding osteoblast behaviour.

Apatite nanocrystals, which mimic the dimensions of natural bone mineral, were electrosprayed on glass substrates, as a suitable synthetic biomedical material for osteoblast outgrowth was explored. A variety of topographic patterns were deposited and the influence of these designs on osteoblast alignment and cell differentiation was investigated. Patterned cell growth and enhanced cell differentiation were seen. Osteoblasts were also cultured on apatite nanocrystals chemically modified with either carbonate or silicon ions. Enhanced cell proliferation and early formation of mineral nodules were observed on apatite nanocrystals with silicon addition. This work highlights the importance of the combined effects of surface topography and surface chemistry in the guidance of cell behaviour.

The effect of simvastatin on bone formation and ceramic resorption in a peri-implant defect model.

Experimental use of statins as stimulators of bone formation suggests they may have widespread applicability in the field of orthopaedics. With their combined effects on osteoblasts and osteoclasts, statins have the potential to enhance resorption of synthetic materials and improve bone ingrowth. In this study, the effect of oral and local administration of simvastatin to a beta tricalcium phosphate (betaTCP)-filled defect around an implant was compared with recombinant human bone morphogenetic protein 2 (rhBMP2). On hundred and sixty-two Sprague-Dawley rats were assigned to treatment groups: local application of 0.1, 0.9 or 1.7 mg of simvastatin, oral simvastatin at 5, 10 or 50 mg kg(-1) day(-1) for 20 days, local delivery of 1 or 10 microg of rhBMP2, or control. At 6 weeks rhBMP2 increased serum tartrate-resistant acid phosphatase 5b levels and reduced betaTCP area fraction, particle size and number compared with control, suggesting increased osteoclast activity. There was reduced stiffness and increased mechanical strength with this treatment. Local simvastatin resulted in a decreased mineral apposition rate at 6 weeks and increased fibrous area fraction, betaTCP area fraction, particle size and number at 26 weeks. Oral simvastatin had no effect compared with control. Local application of rhBMP2 increased resorption and improved mechanical strength whereas simvastatin was detrimental to healing. Oral simvastatin was ineffective at promoting either ceramic resorption or bone formation. The effect of statins on the repair of bone defects with graft substitute materials is influenced by its bioavailability. Thus, further studies on the optimal delivery system are needed.

The response of osteoblasts to nanocrystalline silicon-substituted hydroxyapatite thin films.

Magnetron co-sputtering has been employed to fabricate thin nanocrystalline coatings of silicon-substituted hydroxyapatite (SiHA) of different Si compositions: 0.8 wt%, 2.2 wt%, and 4.9 wt%. A human osteoblast-like (HOB) cell model was used to study the long-term interaction between the HOB cells and coatings in vitro. Results showed that the number of cells growing on all coated titanium (Ti) samples were statistically significantly higher than on uncoated Ti. In addition, HOB cells growing on all SiHA surfaces displayed enhanced cell spreading, with extensive extracellular matrix synthesis. DNA staining revealed normal phenotype nuclear morphology for HOB cells, with several dense chromosomes surrounded by a periphery of intact nuclear membrane. Furthermore, immunofluorescent staining indicated that cells showed improved adhesion on the coated surfaces with increasing Si content, developing mature cytoskeletons with numerous distinct and well-defined actin stress fibres in the cell membranes. Results also demonstrated that the bone mineralisation process was greatest in the presence of the highest Si level (4.9 wt%). However, at very early culturing time point, cells did not attach so readily on the surface of this coating due to rapid dissolution. Thus, this work suggests that a Si content of 2.2 wt% may be the optimum loading to improve the bioactive property of HA thin films.

Adsorption of Amorphous Silica Nanoparticles onto Hydroxyapatite Surfaces Differentially Alters Surfaces Properties and Adhesion of Human Osteoblast Cells.

Silicon (Si) is suggested to be an important/essential nutrient for bone and connective tissue health. Silicon-substituted hydroxyapatite (Si-HA) has silicate ions incorporated into its lattice structure and was developed to improve attachment to bone and increase new bone formation. Here we investigated the direct adsorption of silicate species onto an HA coated surface as a cost effective method of incorporating silicon on to HA surfaces for improved implant osseointegration, and determined changes in surface characteristics and osteoblast cell adhesion. Plasma-sprayed HA-coated stainless steel discs were incubated in silica dispersions of different concentrations (0-42 mM Si), at neutral pH for 12 h. Adsorbed Si was confirmed by XPS analysis and quantified by ICP-OES analysis following release from the HA surface. Changes in surface characteristics were determined by AFM and measurement of surface wettability. Osteoblast cell adhesion was determined by vinculin plaque staining. Maximum Si adsorption to the HA coated disc occurred after incubation in the 6 mM silica dispersion and decreased progressively with higher silica concentrations, while no adsorption was observed with dispersions below 6 mM Si. Comparison of the Si dispersions that produced the highest and lowest Si adsorption to the HA surface, by TEM-based analysis, revealed an abundance of small amorphous nanosilica species (NSP) of ~1.5 nm in diameter in the 6 mM Si dispersion, with much fewer and larger NSP in the 42 mM Si dispersions. 29Si-NMR confirmed that the NSPs in the 6 mM silica dispersion were polymeric and similar in composition to the larger NSPs in the 42 mM Si dispersion, suggesting that the latter were aggregates of the former. Amorphous NSP adsorbed from the 6 mM dispersion on to a HA-coated disc surface increased the surface's water contact angle by 53°, whereas that adsorbed from the 42 mM dispersion decreased the contact angle by 18°, indicating increased and decreased hydrophobicity, respectively. AFM showed an increase in surface roughness of the 6 mM Si treated surface, which correlated well with an increase in number of vinculin plaques. These findings suggest that NSP of the right size (relative to charge) adsorb readily to the HA surface, changing the surface characteristics and, thus, improving osteoblast cell adhesion. This treatment provides a simple way to modify plasma-coated HA surfaces that may enable improved osseointegration of bone implants.