A Review of Strategies to Improve Biomechanical Fixation in the Cervical Spine

Study Design Systematic review. Objectives Review the surgical techniques and construct options aimed at improving the biomechanical strength of cervical constructs. Methods A systematic review was conducted in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. A search of the MEDLINE, Embase, and Cochrane Library databases was performed to identify all studies examining biomechanical strategies utilized in the osteoporotic cervical spine. Screening was performed in duplicate for all stages of the review process. Results An initial search returned 3887 articles. After deletion of duplications and review of abstracts and full text, 39 articles met inclusion criteria. Overall, the surgical techniques reviewed aimed at obtaining rigid fixation in the setting of poor bone quality, or dispersing the forces at the bone-implant interface. We identified 6 key techniques to improve biomechanical fixation. These include bicortical fixation, appropriate screw selection (size and trajectory), PMMA augmentation, load sharing techniques, consideration of ancillary fixation around the occipitocervical junction, and supplementing the construct with post-operative collar or halo. Conclusion The summation of the literature highlights a framework of modalities available to surgeons to improve biomechanical fixation in the cervical spine. While these may improve construct strength in the setting of osteoporosis, there is a paucity of evidence available to make recommendations in this patient population.

New Zealand's extinct giant raptor ( Hieraaetus moorei ) killed like an eagle, ate like a condor

The extinct Haast's eagle or harpagornis ( Hieraaetus moorei ) is the largest known eagle. Historically, it was first considered a predator, then a scavenger, but most recent authors have favoured an active hunting ecology. However, the veracity of proposed similarities to carrion feeders has not been thoroughly tested. To infer feeding capability and behaviour in harpagornis, we used geometric morphometric and finite-element analyses to assess the shape and biomechanical strength of its neurocranium, beak and talons in comparison to five extant scavenging and predatory birds. The neurocranium of harpagornis is vulture-like in shape whereas its beak is eagle-like. The mechanical performance of harpagornis is closer to extant eagles under biting loads but is closest to the Andean condor ( Vultur gryphus ) under extrinsic loads simulating prey capture and killing. The talons, however, are eagle-like and even for a bird of its size, able to withstand extremely high loads. Results are consistent with the proposition that, unlike living eagles, harpagornis habitually killed prey larger than itself, then applied feeding methods typical of vultures to feed on the large carcasses. Decoupling of the relationship between neurocranium and beak shape may have been linked to rapid evolution.

Effect of knot location on the biomechanical strength and gapping characteristics of ex vivo canine gastrocnemius tenorrhaphy constructs

OBJECTIVE To evaluate the effect of knot location on the biomechanical strength and gapping characteristics of ex vivo canine gastrocnemius tenorrhaphy constructs. SAMPLE 36 cadaveric gastrocnemius tendons from 18 adult dogs. PROCEDURES Tendons were randomly assigned to 3 groups (12 tendons/group) and sharply transected and repaired by means of a core locking-loop suture with the knot at 1 of 3 locations (exposed on the external surface of the tendon, buried just underneath the external surface of the tendon, or buried internally between the apposed tendon ends). All repairs were performed with size-0 polypropylene suture. All constructs underwent a single load-to-failure test. Yield, failure, and peak forces, mode of failure, and forces required for 1- and 3-mm gap formation were compared among the 3 knot-location groups. RESULTS Mean yield, failure, and peak forces and mean forces required for 1- and 3-mm gap formation did not differ significantly among the 3 groups. The mode of failure also did not differ significantly among the 3 groups, and the majority (33/36 [92%]) of constructs failed owing to the suture pulling through the tendinous substance. CONCLUSIONS AND CLINICAL RELEVANCE Final knot location did not significantly affect the biomechanical strength and gapping characteristics of canine gastrocnemius tenorrhaphy constructs. Therefore, all 3 evaluated knot locations may be acceptable for tendon repair in dogs. In vivo studies are necessary to further elucidate the effect of knot location in suture patterns commonly used for tenorrhaphy on tendinous healing and collagenous remodeling at the repair site.

Nanog/NFATc1/Osterix signaling pathway-mediated promotion of bone formation at the tendon–bone interface after ACL reconstruction with De-BMSCs transplantation

Background Bone formation plays an important role in early tendon–bone healing after anterior cruciate ligament reconstruction (ACLR). Dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) have enhanced osteogenic potential. This study aimed to investigate the effect of De-BMSCs transplantation on the promotion of bone formation at the tendon–bone interface after ACLR and to further explore the molecular mechanism of the enhanced osteogenic potential of De-BMSCs. Methods BMSCs from the femurs and tibias of New Zealand white rabbits were subjected to osteogenic induction and then cultured in medium without osteogenic factors; the obtained cell population was termed De-BMSCs. De-BMSCs were induced to undergo osteo-, chondro- and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. An ACLR model with a semitendinosus tendon was established in rabbits, and the animals were divided into a control group, BMSCs group, and De-BMSCs group. At 12 weeks after surgery, the rabbits in each group were sacrificed to evaluate tendon–bone healing by histologic staining, micro-computed tomography (micro-CT) examination, and biomechanical testing. During osteogenic differentiation of De-BMSCs, an siRNA targeting nuclear factor of activated T-cells 1 (NFATc1) was used to verify the molecular mechanism of the enhanced osteogenic potential of De-BMSCs. Results De-BMSCs exhibited some properties similar to BMSCs, including multiple differentiation potential and cell surface markers. Bone formation at the tendon–bone interface in the De-BMSCs group was significantly increased, and biomechanical strength was significantly improved. During the osteogenic differentiation of De-BMSCs, the expression of Nanog and NFATc1 was synergistically increased, which promoted the interaction of NFATc1 and Osterix, resulting in increased expression of osteoblast marker genes such as COL1A, OCN, and OPN. Conclusions De-BMSCs transplantation could promote bone formation at the tendon–bone interface after ACLR and improve the biomechanical strength of the reconstruction. The Nanog/NFATc1/Osterix signaling pathway mediated the enhanced osteogenic differentiation efficiency of De-BMSCs.

Correction of refractive disorders in the surgical treatment of keratoconus by MyoRing implantation

Keratoconus is a progressive degenerative disease in which, due to the weakening of the biomechanical strength of the cornea, its cone-shaped deformation occurs, leading to the development of induced myopia and astigmatism, as well as to a decrease in corrected visual acuity. Treatment of this disease consists in achieving stabilization of the process by strengthening the structure of the cornea, as well as in correcting refractive disorders caused by corneal deformation. Purpose. The purpose is to evaluate the effectiveness of correction of refractive disorders by implanting a closed MyoRing ring in the corneal stroma of patients with keratoconus. Material and methods. The data of 98 MyoRing implantation operations using CISIS technology using the PoketMaker ultraceratom for stage 3-4 keratoconus were analyzed. The observation period is up to 9 years. The initial myopia averaged -9.23 D ±3.82, astigmatism-6.13 ±2.51. Results. Stabilization of the refractive effect occurred usually within 3-6 months after surgery. On average, the following correction of refractive disorders was achieved: myopia-8.14 D ± 2.67 and astigmatism-4.28 D ± 2.12. Keratometry indicators also in most cases stabilized within 3-6 months after surgery and remained unchanged throughout the entire follow-up period. Conclusions. Implantation of a closed MyoRing ring in keratoconus makes it possible to significantly correct refractive disorders and prevents further progression of the disease. Key words: keratoconus, MyoRing, SISI, ring implantation in keratoconus.

Adipose-Derived Stem Cell Sheets Improve Early Biomechanical Graft Strength in Rabbits After Anterior Cruciate Ligament Reconstruction

Background: Although various reconstruction techniques are available for anterior cruciate ligament (ACL) injuries, a long recovery time is required before patients return to sports activities, as the reconstructed ACL requires time to regain strength. To date, several studies have reported use of mesenchymal stem cells in orthopaedic surgery; however, no studies have used adipose-derived stem cell (ADSC) sheets in ACL reconstruction (ACLR). Hypothesis: ADSC sheet transplantation can improve biomechanical strength of the autograft used in ACLR. Study Design: Controlled laboratory study. Methods: A total of 68 healthy Japanese white rabbits underwent unilateral ACLR with a semitendinosus tendon autograft after random enrollment into a control group (no sheet; n = 34) and a sheet group (ADSC sheet; n = 34). At 2, 4, 8, 16, and 24 weeks after surgery, rabbits in each group were sacrificed to evaluate tendon-bone healing using histological staining, micro–computed tomography, and biomechanical testing. At 24 weeks, scanning transmission electron microscopy of the graft midsubstance was performed. Results: The ultimate failure load for the control and sheet groups, respectively, was as follows: 17.2 ± 5.5 versus 37.3 ± 10.3 ( P = .01) at 2 weeks, 28.6 ± 1.9 versus 47.4 ± 10.4 ( P = .003) at 4 weeks, 53.0 ± 14.3 versus 48.1 ± 9.3 ( P = .59) at 8 weeks, 66.2 ± 9.3 versus 95.2 ± 43.1 ( P = .24) at 16 weeks, and 66.7 ± 27.3 versus 85.3 ± 29.5 ( P = .39) at 24 weeks. The histological score was also significantly higher in the sheet group compared with the control group at early stages up to 8 weeks. On micro–computed tomography, relative to the control group, the bone tunnel area was significantly narrower in the sheet group at 4 weeks, and the bone volume/tissue volume of the tendon-bone interface was significantly greater at 24 weeks. Scanning transmission electron microscopy at 24 weeks indicated that the mean collagen fiber diameter in the midsubstance was significantly greater, as was the occupation ratio of collagen fibers per field of view, in the sheet group. Conclusion: ADSC sheets improved biomechanical strength, prevented bone tunnel enlargement, and promoted tendon-bone interface healing and graft midsubstance healing in an in vivo rabbit model. Clinical Relevance: ADSC sheets may be useful for early tendon-bone healing and graft maturation in ACLR.

A Mouse Model of Brittle Cornea Syndrome caused by mutation in Zfp469

Brittle Cornea Syndrome (BCS) is a rare recessive condition characterised by extreme thinning of the cornea and sclera. BCS results from loss-of-function mutations in the poorly understood genes ZNF469 or PRDM5. In order to determine the function of ZNF469 and to elucidate pathogenic mechanisms, we used genome editing to recapitulate a human ZNF469 BCS mutation in the orthologous mouse gene, Zfp469. Ophthalmic phenotyping showed that homozygous Zfp469 mutation causes significant central and peripheral corneal thinning arising from reduced stromal thickness. Expression of key components of the corneal stroma in primary keratocytes from Zfp469BCS/BCS mice is affected, including decreased Col1a1 and Col1a2 expression. This alters the type I:type V collagen ratio and results in collagen fibrils with smaller diameter and increased fibril density in homozygous mutant corneas, correlating with decreased biomechanical strength in the cornea. Cell-derived matrices generated by primary keratocytes show reduced deposition of type I collagen offering an in vitro model for stromal dysfunction. Work remains to determine whether modulating ZNF469 activity will have therapeutic benefit in BCS or in conditions such as keratoconus where the cornea thins progressively.

A Mouse Model of Brittle Cornea Syndrome caused by mutation in Zfp469.

Brittle Cornea Syndrome (BCS) is a rare recessive condition characterised by extreme thinning of the cornea and sclera. BCS results from loss-of-function mutations in the poorly understood genes ZNF469 or PRDM5. In order to determine the function of ZNF469 and to elucidate pathogenic mechanisms, we used genome editing to recapitulate a human ZNF469 BCS mutation in the orthologous mouse gene, Zfp469. Ophthalmic phenotyping showed that homozygous Zfp469 mutation causes significant central and peripheral corneal thinning arising from reduced stromal thickness. Expression of key components of the corneal stroma in primary keratocytes from Zfp469BCS/BCS mice is affected, including decreased Col1a1 and Col1a2 expression. This alters the type I:type V collagen ratio and results in collagen fibrils with smaller diameter and increased fibril density in homozygous mutant corneas, correlating with decreased biomechanical strength in the cornea. Cell-derived matrices generated by primary keratocytes show reduced deposition of type I collagen offering an in vitro model for stromal dysfunction. Work remains to determine whether modulating ZNF469 activity will have therapeutic benefit in BCS or in conditions such as keratoconus where the cornea thins progressively.

Nanog/NFATc1/Osterix signaling pathway-mediated promotion of bone formation at the tendon-bone interface after ACL reconstruction with De-BMSCs transplantation

Background: Bone formation plays an important role in early tendon-bone healing after anterior cruciate ligament reconstruction (ACLR). Dedifferentiated osteogenic bone marrow mesenchymal stem cells (De-BMSCs) have enhanced osteogenic potential. This study aimed to investigate the effect of De-BMSCs transplantation on the promotion of bone formation at the tendon-bone interface after ACLR and to further explore the molecular mechanism of the enhanced osteogenic potential of De-BMSCs.Methods: BMSCs from the femurs and tibias of New Zealand White rabbits were subjected to osteogenic induction and then cultured in medium without osteogenic factors; the obtained cell population was termed De-BMSCs. De-BMSCs were induced to undergo osteo-, chondro- and adipo-differentiation in vitro to examine the characteristics of primitive stem cells. An ACLR model with a semitendinosus tendon was established in rabbits, and the animals were divided into a control group, BMSCs group and De-BMSCs group. At 12 weeks after surgery, the rabbits in each group were sacrificed to evaluate tendon-bone healing by histologic staining, micro–computed tomography (micro-CT) examination, and biomechanical testing. During osteogenic differentiation of De-BMSCs, an siRNA targeting nuclear factor of activated T cells 1 (NFATc1) was used to verify the molecular mechanism of the enhanced osteogenic potential of De-BMSCs.Results: De-BMSCs exhibited some properties similar to BMSCs, including multiple differentiation potential and cell surface markers. Bone formation at the tendon-bone interface in the De-BMSCs group was significantly increased, and biomechanical strength was significantly improved. During the osteogenic differentiation of De-BMSCs, the expression of Nanog and NFATc1 was synergistically increased, which promoted the interaction of NFATc1 and Osterix, resulting in increased expression of osteoblast marker genes such as COL1A, OCN, and OPN.Conclusions: De-BMSCs transplantation could promote bone formation at the tendon-bone interface after ACLR and improve the biomechanical strength of the reconstruction. The Nanog/NFATc1/Osterix signaling pathway mediated the enhanced osteogenic differentiation efficiency of De-BMSCs.