No abstract

Calcium phosphate cement (CPC) sets in situ with intimate adaptation to the contours of defect surfaces, and forms an implant having a structure and composition similar to hydroxyapatite, the putative mineral in teeth and bones. The objective of the present study was to develop an injectable CPC using dicalcium phosphate dihydrate (DCPD) with a high solubility for rapid setting. Two agents were incorporated to impart injectability and fast-hardening to the cement: a hardening accelerator (sodium phosphate) and a gelling agent (hydroxypropyl methylcellulose, HPMC). The cement with DCPD was designated as CPC(D), and the conventional cement was referred to as CPC(A). Using water without sodium phosphate, CPC(A) had a setting time of 82 +/- 6 min. In contrast, CPC(D) exhibited rapid setting with a time of 17 +/- 1 min. At 0.2 mol/L sodium phosphate, setting time for CPC(D) was 15 +/- 1 min, significantly faster than 40 +/- 2 min for CPC(A) (Tukey's at 0.95). Sodium phosphate decreased the paste injectability (measured as the paste mass extruded from the syringe divided by the original paste mass inside the syringe). However, the addition of HPMC dramatically increased the paste injectability. For CPC(D), the injectability was increased from 65% +/- 12% without HPMC to 98% +/- 1% with 1% HPMC. Injectability of CPC(A) was also doubled to 99% +/- 1%. The injectable and rapid-setting CPC(D) possessed flexural strength and elastic modulus values overlapping the reported values for sintered porous hydroxyapatite implants and cancellous bone. In summary, the rapid setting and relatively high strength and elastic modulus of CPC(D) should help the graft to quickly attain strength and geometrical integrity within a short period of time postoperatively. Furthermore, the injectability of CPC(D) may have potential for procedures involving defects with limited accessibility or narrow cavities, when there is a need for precise placement of the paste, and when using minimally invasive surgical techniques.

Calcium phosphate cement (CPC) sets in situ and forms apatite with excellent osteoconductivity and bone-replacement capability. The objectives of this study were to formulate an injectable tetracalcium phosphate-dicalcium phosphate cement (CPC D ), and investigate the powder/liquid ratio and needlesize effects. The injection force (mean ± SD; n = 4) to extrude the paste increased from (8 ± 2) N using a 10-gauge needle to (144 ± 17) N using a 21-gauge needle (p < 0.05). With the 10-gauge needle, the mass percentage of extruded paste was (95 ± 4)% at a powder/liquid ratio of 3; it decreased to (70 ± 12)% at powder/liquid = 3.5 (p < 0.05). A relationship was established between injection force, F, and needle lumen cross-sectional area, A: F = 5.0 + 38.7/A 0.8 . Flexural strength, S, (mean ± SD; n = 5) increased from (5.3 ± 0.8) MPa at powder/liquid = 2 to (11.0 ± 0.8) MPa at powder/ liquid = 3.5 (p < 0.05). Pore volume fraction, P, ranged from 62.4% to 47.9%. A relationship was established: S = 47.7 × (1 -P) 2.3 . The strength of the injectable CPC D matched/exceeded the reported strengths of sintered porous hydroxyapatite implants that required machining. The novel injectable CPC D with a relatively high strength may be useful in filling defects with limited accessibility such as periodontal repair and tooth root-canal fillings, and in minimally-invasive techniques such as percutaneous vertebroplasty to fill the lesions and to strengthen the osteoporotic bone.

Platelet-rich plasma (PRP) is defined as a volume of plasma with a platelet concentration higher than the average in peripheral blood. Many basic, preclinical and even clinical case studies and trials report PRP’s ability to improve musculoskeletal conditions including osteoarthritis, but paradoxically, just as many conclude it has no effect. The purpose of this narrative review is to discuss the available relevant evidence that supports the clinical use of PRP in osteoarthritis, highlighting those variables we perceive as critical. Here, recent systematic reviews and meta-analyses were used to identify the latest randomized controlled trials (RCTs) testing a PRP product as an intra-articular treatment for knee osteoarthritis, compared with an intra-articular control (mostly hyaluronic acid). Conclusions in the identified RCTs are examined and compared. In total, five recent meta-analyses and systematic reviews were found meeting the above criteria. A total of 19 individual trials were identified in the five reviews but only 9 were level of evidence I RCTs, and many had moderate or high risks of bias. At present, results from these RCTs seem to favor PRP use over other intra-articular treatments to improve pain scales in the short and medium term (6–12 months), but the overall level of evidence is low. As a result, clinical effectiveness of PRP for knee osteoarthritis treatment is still under debate. This is, prominently, the result of a lack of standardization of PRP products, scarceness of high quality RCTs not showing high risks of bias, and poor patient stratification for inclusion in the RCTs.

Calcium phosphate cement (CPC) sets in situ to form resorbable hydroxyapatite with chemical and crystallographic similarity to the apatite in human bones, hence it is highly promising for clinical applications. The objective of the present study was to develop a CPC that is fast setting and has high strength in the early stages of implantation. Two approaches were combined to impart high early strength to the cement: the use of dicalcium phosphate dihydrate with a high solubility (which formed the cement CPC(D)) instead of anhydrous dicalcium phosphate (which formed the conventional cement CPC(A)), and the incorporation of absorbable fibers. A 2 x 8 design was tested with two materials (CPC(A) and CPC(D)) and eight levels of cement reaction time: 15 min, 30 min, 1 h, 1.5 h, 2 h, 4 h, 8 h, and 24 h. An absorbable suture fiber was incorporated into cements at 25% volume fraction. The Gilmore needle method measured a hardening time of 15.8 min for CPC(D), five-fold faster than 81.5 min for CPC(A), at a powder:liquid ratio of 3:1. Scanning electron microscopy revealed the formation of nanosized rod-like hydroxyapatite crystals and platelet crystals in the cements. At 30 min, the flexural strength (mean +/- standard deviation; n = 5) was 0 MPa for CPC(A) (the paste did not set), (4.2 +/- 0.3) MPa for CPC(D), and (10.7 +/- 2.4) MPa for CPC(D)-fiber specimens, significantly different from each other (Tukey's at 0.95). The work of fracture (toughness) was increased by two orders of magnitude for the CPC(D)-fiber cement. The high early strength matched the reported strength for cancellous bone and sintered porous hydroxyapatite implants. The composite strength S(c) was correlated to the matrix strength S(m): S(c) = 2.16S(m). In summary, substantial early strength was imparted to a moldable, self-hardening and resorbable hydroxyapatite via two synergistic approaches: dicalcium phosphate dihydrate, and absorbable fibers. The new fast-setting and strong cement may help prevent catastrophic fracture or disintegration in moderate stress-bearing bone repairs.

Calcium phosphate cement (CPC) has in situ-setting ability and bioactivity, but the brittleness and low strength limit CPC to only non-load-bearing bone repairs. Human umbilical cord mesenchymal stem cells (hUCMSCs) can be harvested without an invasive procedure required for the commonly studied bone marrow MSCs. However, little has been reported on hUCMSC delivery via bioactive scaffolds for bone tissue engineering. The objectives of this study were to develop CPC scaffolds with improved resistance to fatigue and fracture, and to investigate hUCMSC delivery for bone tissue engineering. In fast fracture, CPC with 15% chitosan and 20% polyglactin fibers (CPC-chitosanfiber scaffold) had flexural strength of 26 MPa, higher than 10 MPa for CPC control (p < 0.05). In cyclic loading, CPC-chitosan-fiber specimens that survived 2 × 10 6 cycles had the maximum stress of 10 MPa, compared to 5 MPa of CPC control. CPC-chitosan-fiber specimens that failed after multiple cycles had a mean stress-to-failure of 9 MPa, compared to 5.8 MPa for CPC control (p < 0.05). hUCMSCs showed excellent viability when seeded on CPC and CPC-chitosan-fiber scaffolds. The percentage of live cells reached 96-99%. Cell density was about 300 cells/mm 2 at day 1; it proliferated to 700 cells/mm 2 at day 4. Wst-1 assay showed that the stronger CPC-chitosan-fiber scaffold had hUCMSC viability that matched the CPC control (p > 0.1). In summary, this study showed that chitosan and polyglactin fibers substantially increased the fatigue resistance of CPC, and that hUCMSCs had excellent proliferation and viability on the scaffolds.

NaSH and GYY4137 show anti-inflammatory and anti-catabolic properties when added to IL1β activated osteoarthritic CHs. Supplementation with exogenous H2S sources can regulate the expression of relevant genes in OA pathogenesis and progression, counteracting IL1β pro-inflammatory signals that lead to cartilage destruction in part by reducing NFκB activation.

Calcium phosphate cement (CPC) is highly promising for clinical uses due to its in situ-setting ability, excellent osteoconductivity and bone-replacement capability. However, the low strength limits its use to non-load-bearing applications. The objectives of this study were to develop a layered CPC structure by combining a macroporous CPC layer with a strong CPC layer, and to investigate the effects of porosity and layer thickness ratios. The rationale was for the macroporous layer to accept tissue ingrowth, while the fiber-reinforced strong layer would provide the needed early-strength. A biopolymer chitosan was incorporated to strengthen both layers. Flexural strength, S (mean±sd; n = 6) of CPC-scaffold decreased from (9.7±1.2) to (1.8±0.3) MPa (p<0.05), when the porosity increased from 44.6% to 66.2%. However, with a strong-layer reinforcement, S increased to (25.2±6.7) and (10.0±1.4) MPa, respectively, at these two porosities. These strengths matched/exceeded the reported strengths of sintered porous hydroxyapatite implants and cancellous bone. Relationships were established between S and the ratio of strong layer thickness/specimen thickness, a/h:S = (17.6 a/h +3.2) MPa. The scaffold contained macropores with a macropore length (mean±sd; n = 147) of (183 ±73) μm, suitable for cell infiltration and tissue ingrowth. Nano-sized hydroxyapatite crystals were observed to form the scaffold matrix of CPC with chitosan. In summary, a layered CPC implant, combining a macroporous CPC with a strong CPC, was developed. Mechanical strength and macroporosity are conflicting requirements. However, the novel functionally graded CPC enabled a relatively high strength and macroporosity to be simultaneously achieved. Such an in situ-hardening nano-apatite may be useful in moderate stress-bearing applications, with macroporosity to enhance tissue ingrowth and implant resorption.