Effects of BMP-12-releasing sutures on Achilles tendon healing.

Tendon healing is a complex coordinated event orchestrated by numerous biologically active proteins. Unfortunately, tendons have limited regenerative potential and as a result, repair may be protracted months to years. Current treatment strategies do not offer localized delivery of biologically active proteins, which may result in reduced therapeutic efficacy. Surgical sutures coated with nanostructured minerals may provide a potentially universal tool to efficiently incorporate and deliver biologically active proteins directly to the wound. Additionally, previous reports indicated that treatment with bone morphogenetic protein-12 (BMP-12) improved tendon healing. Based on this information, we hypothesized that mineral-coated surgical sutures may be an effective platform for localized BMP-12 delivery to an injured tendon. The objective of this study was, therefore, to elucidate the healing effects of mineral-coated sutures releasing BMP-12 using a rat Achilles healing model. The effects of BMP-12-releasing sutures were also compared with standard BMP-12 delivery methods, including delivery of BMP-12 through collagen sponge or direct injection. Rat Achilles tendons were unilaterally transected and repaired using BMP-12-releasing suture (0, 0.15, 1.5, or 3.0 μg), collagen sponge (0 or 1.5 μg BMP-12), or direct injection (0 or 1.5 μg). By 14 days postinjury, repair with BMP-12-releasing sutures reduced the appearance of adhesions to the tendon and decreased total cell numbers. BMP-12 released from sutures and collagen sponge also tended to improve collagen organization when compared with BMP-12 delivered through injection. Based on these results, the release of a protein from sutures was able to elicit a biological response. Furthermore, BMP-12-releasing sutures modulated tendon healing, and the delivery method dictated the response of the healing tissue to BMP-12.

[1]  K. Royalty,et al.  Coating with a Modular Bone Morphogenetic Peptide Promotes Healing of a Bone-Implant Gap in an Ovine Model , 2012, PloS one.

[2]  Ray Vanderby,et al.  Quantification of collagen organization using fractal dimensions and Fourier transforms. , 2012, Acta histochemica.

[3]  Scott J. Hollister,et al.  Controllable mineral coatings on PCL scaffolds as carriers for growth factor release. , 2012, Biomaterials.

[4]  H. Seeherman,et al.  Treatment with rhBMP12 or rhBMP13 increase the rate and the quality of rat Achilles tendon repair , 2011, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[5]  K. Eliceiri,et al.  Quantification of Collagen Organization and Extracellular Matrix Factors within the Healing Ligament , 2011, Microscopy and Microanalysis.

[6]  M. Markel,et al.  Histologic evaluation of suture material loaded with basic fibroblast growth factor (bFGF) on acute rotator cuff repair in an ovine model , 2011 .

[7]  D. Hutmacher,et al.  Spatiotemporal delivery of bone morphogenetic protein enhances functional repair of segmental bone defects. , 2011, Bone.

[8]  Y. Shih,et al.  BMP‐2 suppresses renal interstitial fibrosis by regulating epithelial–mesenchymal transition , 2011, Journal of cellular biochemistry.

[9]  Mark D. Markel,et al.  Controllable protein delivery from coated surgical sutures , 2010 .

[10]  Scott J Hollister,et al.  Controlled nucleation of hydroxyapatite on alginate scaffolds for stem cell-based bone tissue engineering. , 2010, Journal of biomedical materials research. Part A.

[11]  W. Murphy,et al.  Sustained plasmid DNA release from dissolving mineral coatings. , 2010, Acta biomaterialia.

[12]  M. Markel,et al.  Influence of hydroxyapatite-coated and growth factor-releasing interference screws on tendon-bone healing in an ovine model. , 2009, Arthroscopy : the journal of arthroscopic & related surgery : official publication of the Arthroscopy Association of North America and the International Arthroscopy Association.

[13]  W. Murphy,et al.  Growth of hydroxyapatite coatings on biodegradable polymer microspheres. , 2009, ACS applied materials & interfaces.

[14]  S. Bhang,et al.  Long-term delivery enhances in vivo osteogenic efficacy of bone morphogenetic protein-2 compared to short-term delivery. , 2008, Biochemical and biophysical research communications.

[15]  S. Bowman,et al.  The effect of growth differentiation factor-5-coated sutures on tendon repair in a rat model. , 2007, Journal of shoulder and elbow surgery.

[16]  Xueli Yuan,et al.  Endothelial-to-mesenchymal transition contributes to cardiac fibrosis , 2007, Nature Medicine.

[17]  N. Ichinose,et al.  Formation of a FGF-2 and calcium phosphate composite layer on a hydroxyapatite ceramic for promoting bone formation , 2007, Biomedical materials.

[18]  Jordi Puiggalí,et al.  Loading and release of ibuprofen in multi- and monofilament surgical sutures. , 2006, Macromolecular bioscience.

[19]  S. Katoh,et al.  Effects of monofilament nylon coated with basic fibroblast growth factor on endogenous intrasynovial flexor tendon healing. , 2006, The Journal of hand surgery.

[20]  J. Wozney,et al.  Periodontal repair in dogs: effect of recombinant human bone morphogenetic protein-12 (rhBMP-12) on regeneration of alveolar bone and periodontal attachment. , 2004, Journal of clinical periodontology.

[21]  A. Boccaccini,et al.  Development and characterisation of silver-doped bioactive glass-coated sutures for tissue engineering and wound healing applications. , 2004, Biomaterials.

[22]  Kai-Ming Chan,et al.  The roles of bone morphogenetic protein (BMP) 12 in stimulating the proliferation and matrix production of human patellar tendon fibroblasts. , 2003, Life Science.

[23]  Matthew J. Silva,et al.  BMP‐12 gene transfer augmentation of lacerated tendon repair , 2001, Journal of orthopaedic research : official publication of the Orthopaedic Research Society.

[24]  W. Richter,et al.  A Growth and Differentiation Factor-5 (GDF-5)-coated Suture Stimulates Tendon Healing in an Achilles Tendon Model in Rats , 2001, Growth factors.

[25]  G. Karsenty,et al.  The family of bone morphogenetic proteins. , 2000, Kidney international.

[26]  X. Marchandise,et al.  Adsorption and release of insulin-like growth factor-I on porous tricalcium phosphate implant. , 2000, Journal of biomedical materials research.

[27]  S. Schwendeman,et al.  Stabilization of proteins encapsulated in injectable poly (lactide-co-glycolide) , 2000, Nature Biotechnology.

[28]  F. Cui,et al.  Antimicrobial effects of metal ions (Ag+, Cu2+, Zn2+) in hydroxyapatite , 1998, Journal of materials science. Materials in medicine.

[29]  V. Rosen,et al.  Bone morphogenetic protein and bone morphogenetic protein gene family in bone formation and repair. , 1998, Clinical orthopaedics and related research.

[30]  I. Ishikawa,et al.  Ectopic bone formation by biphasic calcium phosphate (BCP) combined with recombinant human bone morphogenetic protein-2 (rhBMP-2). , 1997, Journal of medical and dental sciences.

[31]  V. Rosen,et al.  Ectopic induction of tendon and ligament in rats by growth and differentiation factors 5, 6, and 7, members of the TGF-beta gene family. , 1997, The Journal of clinical investigation.

[32]  C. Bünger,et al.  Transforming growth factor-beta 1 stimulates bone ongrowth to weight-loaded tricalcium phosphate coated implants: an experimental study in dogs. , 1996, The Journal of bone and joint surgery. British volume.

[33]  S. N. Timasheff,et al.  The interaction of proteins with hydroxyapatite. III. Mechanism. , 1984, Analytical biochemistry.

[34]  M. J. Gorbunoff The interaction of proteins with hydroxyapatite. I. Role of protein charge and structure. , 1984, Analytical biochemistry.

[35]  G. Bernardi Chromatography of nucleic acids on hydroxyapatite. II. Chromatography of denatured DNA. , 1969, Biochimica et biophysica acta.

[36]  G. Bernardi Chromatography of nucleic acids on hydroxyapatite. I. Chromatography of native DNA. , 1969, Biochimica et biophysica acta.

[37]  G. Bernardi,et al.  Chromatography of polypeptides and proteins on hydroxyapatite columns. , 1968, Biochimica et biophysica acta.

[38]  G. Bernardi Chromatography of Nucleic Acids on Hydroxyapatite , 1965, Nature.

[39]  R. Stephenson A and V , 1962, The British journal of ophthalmology.