title: Repair of segmental ulna defects using a β-TCP implant in combination with a heparan sulfate glycosaminoglycan variant.
abstract: Given the wide spread clinical use of ceramic-based bone void fillers, we sought to determine the efficacy of an FDA-approved β-tricalcium phosphate bone graft substitute (JAX™) in combination with a carboxymethyl cellulose (CMC) handling agent that included a particular heparan glycosaminoglycan (GAG) variant, herein referred to as HS3. Having recently demonstrated efficacy of a combination collagen/HS3 device, we further aimed to determine the support that HS3 could offer a handling agent used to administer a more tissue-relevant bone void filler. This study evaluated the JAX™-HS3 combination device in 1.5 cm critical-sized defects in the ulna bones of 27 male New Zealand White rabbits. Treatment groups consisted of JAX™ applied with CMC alone, or JAX™ with CMC containing either 30 μg or 100 μg of the HS3 GAG. Data based on radiographic, μCT, mechanical, and histological analyses at 4 and 8 weeks post-surgery, clearly demonstrate enhanced new bone formation in the JAX™-HS3 combination treated defects compared to treatment with JAX™ alone. The efficacy of such a combination advocates for inclusion of HS3 in handling agents used in the preparation of various bone void fillers being used in orthopaedic surgery.
  
  
  CONCLUSIONS
  Synthetic bone grafts and demineralized bone matrices are gaining prominence as alternatives to autologous and allogeneic bone grafts and are frequently administered in granular form, necessitating their combination with a handling agent. Typical handling agents include glycerol, gelatin, cellulose, hyaluronic acid and lecithin, formulated as hydrogels, which can be further enhanced by the addition of heparan sulfate (HS) glycosaminoglycans that augment the osteostimulatory properties of the graft. Here we assessed the efficacy of β-TCP granules combined with a hydrogel consisting of carboxymethyl cellulose and the HS variant (HS3) previously shown to enhance osteogenic healing. The data advocates for HS3 to be included during the formulation of hydrogel-based carriers that support the various bone void fillers being used in orthopaedic surgery.
authors.affiliation: Institute of Medical Biology, A(∗)STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: B
authors.initials: B
authors.lastname: Rai
authors.affiliation: Institute of Medical Biology, A(∗)STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: A
authors.initials: A
authors.lastname: Chatterjea
authors.affiliation: Institute of Medical Biology, A(∗)STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: Z X H
authors.initials: ZXH
authors.lastname: Lim
authors.affiliation: Institute of Medical Biology, A(∗)STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: T C
authors.initials: TC
authors.lastname: Tan
authors.affiliation: Institute of Molecular and Cell Biology, A(∗)STAR, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
authors.forename: A A
authors.initials: AA
authors.lastname: Sawyer
authors.affiliation: Institute of Molecular and Cell Biology, A(∗)STAR, 61 Biopolis Drive, Proteos, Singapore 138673, Singapore.
authors.forename: Y Z
authors.initials: YZ
authors.lastname: Hosaka
authors.affiliation: Institute of Medical Biology, A(∗)STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: S
authors.initials: S
authors.lastname: Murali
authors.affiliation: Institute of Medical Biology, A(∗)STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: J J L
authors.initials: JJL
authors.lastname: Lee
authors.affiliation: Smith & Nephew Research Centre, York Science Park, York YO10 5DF, United Kingdom.
authors.forename: S A
authors.initials: SA
authors.lastname: Fenwick
authors.affiliation: Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119074, Singapore.
authors.forename: J H
authors.initials: JH
authors.lastname: Hui
authors.affiliation: Institute of Medical Biology, A(∗)STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore.
authors.forename: V
authors.initials: V
authors.lastname: Nurcombe
authors.affiliation: Institute of Medical Biology, A(∗)STAR, 8A Biomedical Grove, #06-06 Immunos, Singapore 138648, Singapore; Department of Orthopaedic Surgery, Yong Loo Lin School of Medicine, National University of Singapore, 119074, Singapore. Electronic address: simon.cool@imb.a-star.edu.sg.
authors.forename: S M
authors.initials: SM
authors.lastname: Cool
mesh_terms: D000818:Animals; D002130:Calcium Phosphates / Q000008:administration & dosage*; D006025:Glycosaminoglycans / Q000008:administration & dosage*; D006497:Heparan Sulfate / Q000008:administration & dosage*; D008297:Male; D051379:Mice; D019736:Prostheses and Implants; D014457:Ulna / Q000002:abnormalities*; D055114:X-Ray Microtomography
chemical_list: D002130:Calcium Phosphates; D006025:Glycosaminoglycans; D006497:Heparan Sulfate; C485817:beta-tricalcium phosphate
keywords: BMP-2; Bone graft substitute; Bone void fillers; Fracture healing; Glycosaminoglycans; Growth factors; Heparan sulfate