Bioengineering an Osteoinductive Treatment for Bone Healing Disorders: A Small Animal Case Series

William G. Marshall; Cristina Gonzalez-Garcia; Sara Trujillo; Andres Alba-Perez; Peter Childs; David W. Shields; Andrew Tomlinson; Rob Pettitt; Barbro Filliquist; Po-Yen Chou; Matthew J. Dalby; Sandra A. Corr; Manuel Salmeron-Sanchez

doi:10.1055/s-0043-1762900

VCOT Open, Inhaltsverzeichnis

CC BY 4.0 · VCOT Open 2023; 06(01): e41-e51
DOI: 10.1055/s-0043-1762900

Clinical Communication

Bioengineering an Osteoinductive Treatment for Bone Healing Disorders: A Small Animal Case Series

William G. Marshall

¹Small Animal Hospital, School of Veterinary Medicine, University of Glasgow, United Kingdom

²Centre for the Cellular Microenvironment, University of Glasgow, United Kingdom

,

Cristina Gonzalez-Garcia

²Centre for the Cellular Microenvironment, University of Glasgow, United Kingdom

,

Sara Trujillo

²Centre for the Cellular Microenvironment, University of Glasgow, United Kingdom

,

Andres Alba-Perez

²Centre for the Cellular Microenvironment, University of Glasgow, United Kingdom

,

Peter Childs

²Centre for the Cellular Microenvironment, University of Glasgow, United Kingdom

,

David W. Shields

²Centre for the Cellular Microenvironment, University of Glasgow, United Kingdom

³Queen Elizabeth University Hospital, Glasgow, United Kingdom

,

Andrew Tomlinson

⁴Small Animal Teaching Hospital, School of Veterinary Science, University of Liverpool, United Kingdom

,

Rob Pettitt

⁴Small Animal Teaching Hospital, School of Veterinary Science, University of Liverpool, United Kingdom

,

Barbro Filliquist

⁵Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, California, United States

,

Po-Yen Chou

⁵Department of Surgical and Radiological Sciences, School of Veterinary Medicine, University of California Davis, California, United States

,

Matthew J. Dalby

²Centre for the Cellular Microenvironment, University of Glasgow, United Kingdom

,

Sandra A. Corr

¹Small Animal Hospital, School of Veterinary Medicine, University of Glasgow, United Kingdom

,

Manuel Salmeron-Sanchez

²Centre for the Cellular Microenvironment, University of Glasgow, United Kingdom

› Institutsangaben

Abstract

The aim of this article was to study clinical and radiographic outcomes following treatment of bone healing disorders with a novel osteoinductive system that utilizes poly (ethyl acrylate), fibronectin and an ultra-low concentration of recombinant human bone morphogenetic protein-2. A case series of nine dogs and two cats were treated, and clinical records and radiographs were reviewed. Radiographs were scored by two blinded observers using the modified Radiographic Union Score for Tibial Fractures. Long-term follow-up was obtained using the Canine Orthopaedic Index and Feline Musculoskeletal Pain Index. Follow-up data were available for 11 treatments (10 cases). Complications: three minor, three major, one catastrophic (non-union requiring amputation). Lameness median 320 (range: 42–1,082) days postoperatively: ‘sound’ (three cases), ‘subtle’ (two), ‘mild’ (three), ‘moderate’ (one), and ‘non-weightbearing’ (one). The attending clinician judged 9 of 11 treatments achieved radiographic union; modified Radiographic Union Score for Tibial Fractures observers 1 and 2 agreed with the clinician in 8/9 and 5/9 treatments respectively. Long-term Canine Orthopaedic Index scores for five dogs median 650 (range: 544–1,724) days postoperatively: 15/64 (median) for four dogs with acceptable outcomes, 30/64 in one dog with a poor outcome. Feline Musculoskeletal Pain Index scores for two cats 433 and 751 days postoperatively: 48/60 and 60/60. Eight of 10 cases were sound or showed subtle or mild lameness in the short- or long-term, and radiographic union occurred in the majority of treatments.

Keywords

bioengineering - bone morphogenetic protein - cats - dogs - fracture healing

Volltext

Referenzen

References
1 Phillips IR. A survey of bone fractures in the dog and cat. J Small Anim Pract 1979; 20 (11) 661-674
2 Atilola MAO, Sumner-Smith G. Non-union fractures in dogs. J Vet Orthop. 1984; 3: 21-24
3 Marshall WG, Filliquist B, Tzimtzimis E. et al. Delayed union, non-union and mal-union in 442 dogs. Vet Surg 2022; 51 (07) 1087-1095
4 Pinel CB, Pluhar GE. Clinical application of recombinant human bone morphogenetic protein in cats and dogs: a review of 13 cases. Can Vet J 2012; 53 (07) 767-774
5 Massie AM, Kapatkin AS, Fuller MC, Verstraete FJ, Arzi B. Outcome of nonunion fractures in dogs treated with fixation, compression resistant matrix, and recombinant human bone morphogenetic protein-2. Vet Comp Orthop Traumatol 2017; 30 (02) 153-159
6 Vezzoni L, Abrescia P, Vezzoni A. Internal radioulnar fixation for treatment of non-union of proximal radius and ulna fractures in a toy breed dog. Vet Comp Orthop Traumatol Open. 2021; 4: e24-e31
7 Franch J, Barba A, Rappe K, Maazouz Y, Ginebra MP. Use of three-dimensionally printed β-tricalcium phosphate synthetic bone graft combined with recombinant human bone morphogenic protein-2 to treat a severe radial atrophic nonunion in a Yorkshire terrier. Vet Surg 2020; 49 (08) 1626-1631
8 Schmoekel HG, Weber FE, Hurter K. et al. Enhancement of bone healing using non-glycosylated rhBMP-2 released from a fibrin matrix in dogs and cats. J Small Anim Pract 2005; 46 (01) 17-21
9 Govender S, Csimma C, Genant HK. et al; BMP-2 Evaluation in Surgery for Tibial Trauma (BESTT) Study Group. Recombinant human bone morphogenetic protein-2 for treatment of open tibial fractures: a prospective, controlled, randomized study of four hundred and fifty patients. J Bone Joint Surg Am 2002; 84 (12) 2123-2134
10 Brigaud I, Agniel R, Leroy-Dudal J. et al. Synergistic effects of BMP-2, BMP-6 or BMP-7 with human plasma fibronectin onto hydroxyapatite coatings: a comparative study. Acta Biomater 2017; 55: 481-492
11 Yang HS, La W-G, Cho Y-M, Shin W, Yeo G-D, Kim B-S. Comparison between heparin-conjugated fibrin and collagen sponge as bone morphogenetic protein-2 carriers for bone regeneration. Exp Mol Med 2012; 44 (05) 350-355
12 Seeherman H, Wozney JM. Delivery of bone morphogenetic proteins for orthopedic tissue regeneration. Cytokine Growth Factor Rev 2005; 16 (03) 329-345
13 James AW, LaChaud G, Shen J. et al. A review of the clinical side effects of bone morphogenetic protein-2. Tissue Eng Part B Rev 2016; 22 (04) 284-297
14 Woo EJ. Adverse events after recombinant human BMP2 in nonspinal orthopaedic procedures. Clin Orthop Relat Res 2013; 471 (05) 1707-1711
15 Ohara T, Sato T, Shimizu N. et al. Acrylic acid and derivatives. In: Ullmann's Encyclopaedia of Industrial Chemistry. New Jersey, USA: Wiley; 2020
16 Cheng ZA, Alba-Perez A, Gonzalez-Garcia C. et al. Nanoscale coatings for ultralow dose BMP-2-driven regeneration of critical-sized bone defects. Adv Sci 2019; 6: 1800361
17 Mao Y, Schwarzbauer JE. Fibronectin fibrillogenesis, a cell-mediated matrix assembly process. Matrix Biol 2005; 24 (06) 389-399
18 Salmerón-Sánchez M, Rico P, Moratal D, Lee TT, Schwarzbauer JE, García AJ. Role of material-driven fibronectin fibrillogenesis in cell differentiation. Biomaterials 2011; 32 (08) 2099-2105
19 Llopis-Hernández V, Cantini M, González-García C. et al. Material-driven fibronectin assembly for high-efficiency presentation of growth factors. Sci Adv 2016; 2 (08) e1600188
20 Marshall WG, Alba-Perez A, Gonzalez-Garcia C. et al. Bioengineering a novel growth factor system for fracture non-union: first successful treatment of a dog. Poster abstract ECVS Symposium, Budapest, Hungary; 2019
21 Cook JL, Evans R, Conzemius MG. et al. Proposed definitions and criteria for reporting time frame, outcome, and complications for clinical orthopedic studies in veterinary medicine. Vet Surg 2010; 39 (08) 905-908
22 Litrenta J, Tornetta III P, Mehta S. et al. Determination of radiographic healing: an assessment of consistency using RUST and modified RUST in metadiaphyseal fractures. J Orthop Trauma 2015; 29 (11) 516-520
23 Balzer W, Owen R. Survey of 156 police dogs in New Zealand: functional assessment and Canine Orthopaedic Index. Vet Comp Orthop Traumatol 2019; 32 (03) A1-A12
24 Bilic R, Simic P, Jelic M. et al. Osteogenic protein-1 (BMP-7) accelerates healing of scaphoid non-union with proximal pole sclerosis. Int Orthop 2006; 30 (02) 128-134
25 Ronga M, Baldo F, Zappalà G, Cherubino P. Recombinant human bone morphogenetic protein-7 for treatment of long bone non-union: an observational, retrospective, non-randomized study of 105 patients. Injury. Int. J. Care Injured. 2006; 37S: S51-S56
26 Castilla A, Filliquist B, Spriet M. et al. Long-term assessment of bone regeneration in nonunion fractures treated with compression-resistant matrix and recombinant human bone morphogenetic protein-2 in dogs. Vet Comp Orthop Traumatol 2023; 36 (01) 29-38
27 Mills L, Tsang J, Hopper G, Keenan G, Simpson AHRW. The multifactorial aetiology of fracture nonunion and the importance of searching for latent infection. Bone Joint Res 2016; 5 (10) 512-519
28 Govaert GAM, Kuehl R, Atkins BL. et al; Fracture-Related Infection (FRI) Consensus Group. Diagnosing fracture-related infection: current concepts and recommendations. J Orthop Trauma 2020; 34 (01) 8-17
29 Alcantara BM, Minto BW, Franco GG, Lucena DVF, Dias LGGG. Bridge plating for simple tibial fractures treated by minimally invasive plate osteosynthesis. Arq Bras Med Vet Zootec 2021; 73: 589-597
30 Misir A, Uzun E, Kizkapan TB, Yildiz KI, Onder M, Ozcamdalli M. Reliability of RUST and Modifed RUST Scores for the evaluation of union in humeral shaft fractures treated with different techniques. Indian J Orthop 2020; 54 (Suppl. 01) 121-126
31 Kizkapan TB, Misir A, Oguzkaya S, Ozcamdalli M, Uzun E, Sayer G. Reliability of radiographic union scale in tibial fractures and modified radiographic union scale in tibial fractures scores in the evaluation of pediatric forearm fracture union. Jt Dis Relat Surg 2021; 32 (01) 185-191
32 Mısır A, Yıldız KI, Kızkapan TB, Uzun E, Özçamdallı M, Oğuzkaya S. Reliability of RUST and modified RUST scores for evaluation of union in pediatric and adult femoral shaft fractures. Acta Orthop Traumatol Turc 2021; 55 (02) 127-133
33 Saad BN, Zurita D, Li DJ, Dailey H, Yoon RS. . LIporace FA. Bone marrow aspirate concentrate as a reliable adjunct in tibiotalocalcanal fusion: A radiographic modifed RUST score analysis. Ind J Orthop; 2021.
34 Coburn A, Shearer D, Albright P. et al. Evaluating reliability and validity of the modified radiographic union scale for tibia (mRUST) among North American and Tanzanian surgeons. OTA Int; 2020.
35 Bergström A, Johard S, Lee MH, Comin A. Long term prognosis of quality of life in dogs diagnosed with mild to moderate elbow dysplasia in Sweden. Front Vet Sci 2020; 7: 572691