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J Wrist Surg 2023; 12(05): 418-427
DOI: 10.1055/s-0043-1761608
Scientific Article

BMP2 and GDF5 for Compartmentalized Regeneration of the Scapholunate Ligament

Hayman Lui 
1   School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia
2   Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
,
Cedryck Vaquette    *
3   Centre for Oral Regeneration, Reconstruction and Rehabilitation (COR3), School of Dentistry, The University of Queensland, Brisbane, Queensland, Australia
,
Janet M. Denbeigh    *
2   Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
,
Randy Bindra
1   School of Medicine and Dentistry, Griffith University, Gold Coast, Queensland, Australia
4   Department of Orthopaedic Surgery, Gold Coast University Hospital, Gold Coast, Queensland, Australia
,
Andre J. van Wijnen    *
2   Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
5   Department of Biochemistry, University of Vermont, Burlington, Vermont
,
Sanjeev Kakar    *
2   Department of Orthopedic Surgery, Mayo Clinic, Rochester, Minnesota
› Author Affiliations Funding Additional funding was provided by NIH grant R01 AR049069.
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Abstract

Background Chronic injuries to the scapholunate ligament (SLIL) alter carpal kinematics and may progress to early degenerative osteoarthritis. To date, there is no consensus for the best method for SLIL reconstruction. This study aims to assess the use of growth factors (bone morphogenetic protein [BMP]2 and growth and differentiation factor 5 [GDF5]) for compartmentalized regeneration of bone and ligament in this multiphasic scaffold in a rabbit knee model.

Case Description A total of 100 µg of BMP2 and 30 µg of GDF5 were encapsulated into a heparinized gelatin–hyaluronic acid hydrogel and loaded into the appropriate compartment of the multiphasic scaffold. The multiphasic scaffold was implanted to replace the native rabbit medial collateral ligament (n = 16). The rabbits were randomly assigned to two different treatment groups. The first group was immobilized postoperatively with the knee pinned in flexion with K-wires for 4 weeks (n = 8) prior to sacrifice. The second group was immobilized for 4 weeks, had the K-wires removed followed by a further 4 weeks of mobilization prior to sample harvesting.

Literature Review Heterotopic ossification as early as 4 weeks was noted on gross dissection and confirmed by microcomputed tomography and histological staining. This analysis revealed formation of a bony bridge located within and over the ligament compartment in the intra-articular region. Biomechanical testing showed increased ultimate force of the ligament compartment at 4 weeks postimplantation consistent with the presence of bone formation and higher numbers of scaffold failures at the bone–tendon junction. This study has demonstrated that the addition of BMP2 and GDF5 in the bone–ligament–bone (BLB) scaffold resulted in heterotopic bone formation and failure of the ligament compartment.

Clinical Relevance The implantation of a three-dimensional-printed BLB scaffold alone demonstrated superior biomechanical and histological results, and further investigation is needed as a possible clinical reconstruction for the SLIL.

Keywords

Bone-ligament-bone - BMP2 - GDF5 - scapholunate interosseous ligament - compartmentalized regeneration - rabbit knee joint

* These authors contributed equally.




Publication History

Received: 29 August 2022

Accepted: 27 December 2022

Article published online:
28 February 2023

© 2023. Thieme. All rights reserved.

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  • References

  • 1 Rajan PV, Day CS. Scapholunate interosseous ligament anatomy and biomechanics. J Hand Surg Am 2015; 40 (08) 1692-1702
    CrossrefPubMedGoogle Scholar
  • 2 Pappou IP, Basel J, Deal DN. Scapholunate ligament injuries: a review of current concepts. Hand (N Y) 2013; 8 (02) 146-156
    Google Scholar
  • 3 Johnson JE, Lee P, McIff TE, Toby EB, Fischer KJ. Scapholunate ligament injury adversely alters in vivo wrist joint mechanics: an MRI-based modeling study. J Orthop Res 2013; 31 (09) 1455-1460
    CrossrefPubMedGoogle Scholar
  • 4 Rohman EM, Agel J, Putnam MD, Adams JE. Scapholunate interosseous ligament injuries: a retrospective review of treatment and outcomes in 82 wrists. J Hand Surg Am 2014; 39 (10) 2020-2026
    CrossrefPubMedGoogle Scholar
  • 5 Padmore CE, Stoesser H, Langohr GDG, Johnson JA, Suh N. Carpal kinematics following sequential scapholunate ligament sectioning. J Wrist Surg 2019; 8 (02) 124-131
    Article in Thieme ConnectPubMedGoogle Scholar
  • 6 Kauer JM. The interdependence of carpal articulation chains. Acta Anat (Basel) 1974; 88 (04) 481-501
    CrossrefPubMedGoogle Scholar
  • 7 Garcia-Elias M, Lluch AL, Stanley JK. Three-ligament tenodesis for the treatment of scapholunate dissociation: indications and surgical technique. J Hand Surg Am 2006; 31 (01) 125-134
    Google Scholar
  • 8 Lui H, Vaquette C, Denbeigh JM, Bindra R, Kakar S, van Wijnen AJ. Multiphasic scaffold for scapholunate interosseous ligament reconstruction: a study in the rabbit knee. J Orthop Res 2021; 39 (08) 1811-1824
    CrossrefPubMedGoogle Scholar
  • 9 Lui H, Bindra R, Baldwin J, Ivanovski S, Vaquette C. Additively manufactured multiphasic bone-ligament-bone scaffold for scapholunate interosseous ligament reconstruction. Adv Healthc Mater 2019; 8 (14) e1900133
    CrossrefPubMedGoogle Scholar
  • 10 Bouyer M, Lafosse T, Bentejac A. Arthroscopic scapholunate synthetic ligamentoplasty. Arthrosc Tech 2021; 10 (09) e2189-e2198
    CrossrefPubMedGoogle Scholar
  • 11 Sapa MC, Igeta Y, Gouzou S. et al. Arthroscopic scapholunate dorsal capsulodesis: a 30-patient case series comparing postoperative splint immobilization versus immobilization and connected K-wiring. Hand Surg Rehabil 2018; 37 (06) 352-357
    CrossrefPubMedGoogle Scholar
  • 12 Binder AC, Kerfant N, Wahegaonkar AL, Tandara AA, Mathoulin CL. Dorsal wrist capsular tears in association with scapholunate instability: results of an arthroscopic dorsal capsuloplasty. J Wrist Surg 2013; 2 (02) 160-167
    Article in Thieme ConnectPubMedGoogle Scholar
  • 13 Kamal RN, Moore W, Kakar S. Team approach: management of scapholunate instability. JBJS Rev 2019; 7 (02) e2
    CrossrefPubMedGoogle Scholar
  • 14 Kakar S, Logli AL, Ramazanian T, Gaston RG, Fowler JR. Scapholunate ligament 360° procedure. Bone Joint J 2021; 103-B (05) 939-945
    CrossrefPubMedGoogle Scholar
  • 15 Pérez AJ, Jethanandani RG, Vutescu ES, Meyers KN, Lee SK, Wolfe SW. Role of ligament stabilizers of the proximal carpal row in preventing dorsal intercalated segment instability: a cadaveric study. J Bone Joint Surg Am 2019; 101 (15) 1388-1396
    CrossrefPubMedGoogle Scholar
  • 16 Tabata Y. Tissue regeneration based on growth factor release. Tissue Eng 2003; 9 (Suppl. 01) S5-S15
    CrossrefPubMedGoogle Scholar
  • 17 Koria P. Delivery of growth factors for tissue regeneration and wound healing. BioDrugs 2012; 26 (03) 163-175
    CrossrefPubMedGoogle Scholar
  • 18 Cipitria A, Reichert JC, Epari DR. et al. Polycaprolactone scaffold and reduced rhBMP-7 dose for the regeneration of critical-sized defects in sheep tibiae. Biomaterials 2013; 34 (38) 9960-9968
    CrossrefPubMedGoogle Scholar
  • 19 Reichert JC, Cipitria A, Epari DR. et al. A tissue engineering solution for segmental defect regeneration in load-bearing long bones. Sci Transl Med 2012; 4 (141) 141ra93
    CrossrefPubMedGoogle Scholar
  • 20 Cipitria A, Wagermaier W, Zaslansky P. et al. BMP delivery complements the guiding effect of scaffold architecture without altering bone microstructure in critical-sized long bone defects: a multiscale analysis. Acta Biomater 2015; 23: 282-294
    CrossrefPubMedGoogle Scholar
  • 21 Vaquette C, Mitchell J, Fernandez-Medina T, Kumar S, Ivanovski S. Resorbable additively manufactured scaffold imparts dimensional stability to extraskeletally regenerated bone. Biomaterials 2021; 269: 120671
    CrossrefPubMedGoogle Scholar
  • 22 Lui H, Samsonraj RM, Vaquette C. et al. Combination of BMP2 and EZH2 inhibition to stimulate osteogenesis in a 3D bone reconstruction model. Tissue Eng Part A 2021; 27 (15-16): 1084-1098
    CrossrefPubMedGoogle Scholar
  • 23 Lui H, Denbeigh J, Vaquette C. et al. Fibroblastic differentiation of mesenchymal stem/stromal cells (MSCs) is enhanced by hypoxia in 3D cultures treated with bone morphogenetic protein 6 (BMP6) and growth and differentiation factor 5 (GDF5). Gene 2021; 788: 145662
    CrossrefPubMedGoogle Scholar
  • 24 Saiga K, Furumatsu T, Yoshida A. et al. Combined use of bFGF and GDF-5 enhances the healing of medial collateral ligament injury. Biochem Biophys Res Commun 2010; 402 (02) 329-334
    CrossrefPubMedGoogle Scholar
  • 25 Rickert M, Jung M, Adiyaman M, Richter W, Simank HG. A growth and differentiation factor-5 (GDF-5)-coated suture stimulates tendon healing in an Achilles tendon model in rats. Growth Factors 2001; 19 (02) 115-126
    CrossrefPubMedGoogle Scholar
  • 26 Moore YR, Dickinson DP, Wikesjö UM. Growth/differentiation factor-5: a candidate therapeutic agent for periodontal regeneration? A review of pre-clinical data. J Clin Periodontol 2010; 37 (03) 288-298
    CrossrefPubMedGoogle Scholar
  • 27 Hamlet SM, Vaquette C, Shah A, Hutmacher DW, Ivanovski S. 3-Dimensional functionalized polycaprolactone-hyaluronic acid hydrogel constructs for bone tissue engineering. J Clin Periodontol 2017; 44 (04) 428-437
    CrossrefPubMedGoogle Scholar
  • 28 Lui H, Bindra R, Baldwin J, Ivanovski S, Vaquette C. Additively manufactured multiphasic bone-ligament-bone scaffold for scapholunate interosseous ligament reconstruction. Adv Healthc Mater 2019; 8 (14) e1900133
    CrossrefPubMedGoogle Scholar
  • 29 Würgler-Hauri CC, Dourte LM, Baradet TC, Williams GR, Soslowsky LJ. Temporal expression of 8 growth factors in tendon-to-bone healing in a rat supraspinatus model. J Shoulder Elbow Surg 2007; 16 (5, Suppl): S198-S203
    CrossrefPubMedGoogle Scholar
  • 30 Wolfman NM, Hattersley G, Cox K. 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. J Clin Invest 1997; 100 (02) 321-330
    CrossrefPubMedGoogle Scholar
  • 31 Jin L, Li X. Growth differentiation factor 5 regulation in bone regeneration. Curr Pharm Des 2013; 19 (19) 3364-3373
    CrossrefPubMedGoogle Scholar