Development and Characterization of a AuNP-Genipin-Viscoelastic Collagen Material.

Lower back pain is one of the leading causes of disability, affecting 11.9% of the population worldwide and studies have shown that intervertebral disc degeneration is a common cause for chronic lower back pain. We have explored the combination of three components, viscoelastic collagen, genipin, and gold nanoparticles to determine its potential to promote regeneration of the intervertebral disc, specifically for nucleus pulposus regeneration. The goal of this study was to develop, fabricate and characterize different formulations of viscoelastic collagen conjugated with gold nanoparticles and genipin to assess the feasibility as a tissue template. Results demonstrated the successful attachment of gold nanoparticles to the viscoelastic collagen utilizing the genipin crosslinker. For each of the viscoelastic collagen compositions examined, cell biocompatibility was achieved. The results also demonstrated an increase in stiffness of the material with different sizes and concentrations of AuNPs. Results from the TEM and STEM also demonstrated that the viscoelastic collagen that was developed did not display the characteristic D banding pattern of polymerized collagen. The findings from this study could lead to the development of a more efficient and cost-effective treatment for patients with chronic back pain caused by IVD degeneration.

Impact of Genetic and Pharmacologic Inhibition of Myostatin in a Murine Model of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by compromised skeletal integrity, altered microarchitecture, and bone fragility. Current OI treatment strategies focus on bone antiresorptives and surgical intervention with limited effectiveness, and thus identifying alternative therapeutic options remains critical. Muscle is an important stimulus for bone formation. Myostatin, a TGF-ß superfamily myokine, acts through ActRIIB to negatively regulate muscle growth. Recent studies demonstrated the potential benefit of myostatin inhibition with the soluble ActRIIB fusion protein on skeletal properties, although various OI mouse models exhibited variable skeletal responses. The genetic and clinical heterogeneity associated with OI, the lack of specificity of the ActRIIB decoy molecule for myostatin alone, and adverse events in human clinical trials further the need to clarify myostatin's therapeutic potential and role in skeletal integrity. In this study, we determined musculoskeletal outcomes of genetic myostatin deficiency and postnatal pharmacological myostatin inhibition by a monoclonal anti-myostatin antibody (Regn647) in the G610C mouse, a model of mild-moderate type I/IV human OI. In the postnatal study, 5-week-old wild-type and +/G610C male and female littermates were treated with Regn647 or a control antibody for 11 weeks or for 7 weeks followed by a 4-week treatment holiday. Inhibition of myostatin, whether genetically or pharmacologically, increased muscle mass regardless of OI genotype, although to varying degrees. Genetic myostatin deficiency increased hindlimb muscle weights by 6.9% to 34.4%, whereas pharmacological inhibition increased them by 13.5% to 29.6%. Female +/mstn +/G610C (Dbl.Het) mice tended to have similar trabecular and cortical bone parameters as Wt showing reversal of +/G610C characteristics but with minimal effect of +/mstn occurring in male mice. Pharmacologic myostatin inhibition failed to improve skeletal bone properties of male or female +/G610C mice, although skeletal microarchitectural and biomechanical improvements were observed in male wild-type mice. Four-week treatment holiday did not alter skeletal outcomes. © 2020 American Society for Bone and Mineral Research (ASBMR).

Leprdb/+ Dams Protect Wild-type Male Offspring Bone Strength from the Detrimental Effects of a High-Fat Diet.

The prevalence of maternal obesity is increasing at an alarming rate and increases the life-long risk of developing cardiometabolic disease in adult offspring. Leptin, an adipokine, is systemically elevated in the obese milieu. We recently showed that maternal hyperleptinemia without obesity improves offspring insulin sensitivity and glucose tolerance while protecting against weight gain on a high-fat, high-sugar (HFD). Here, we investigate the effect of maternal hyperleptinemia on offspring bone by using 2 independent maternal models. First, we compared wild-type (WT) offspring from severely hyperleptinemic Leprdb/+ (DB/+) dams with those from WT dams. In the second model, WT females were implanted with miniosmotic pumps that released either saline (group SAL) or leptin (group LEP; 650ng/hour) and the WT offspring were compared. At 23 weeks of age, a subset of offspring were challenged with a HFD for 8 weeks. When the offspring were 31 weeks of age, bone geometry, strength, and material properties were investigated. The HFD increased trabecular bone volume but decreased both total breaking strength and material strength of femora from the offspring of WT dams. However, male offspring of DB/+ dams were protected from the detrimental effects of a HFD, while offspring of LEP dams were not. Further material analysis revealed a modest decrease in advanced glycation end product accumulation coupled with increased collagen crosslinking in male offspring from DB/+ dams on a HFD. These data suggest that while maternal leptin may protect bone quality from the effects of a HFD, additional factors of the maternal environment controlled by leptin receptor signaling are likely also involved.

Biomechanical Properties of Bioabsorbable Fixation for Osteochondral Shell Allografts.

This study compares bioabsorbable nail to metal screw fixation of shell osteochondral allograft (OCAs) for compression and shear strength. Cadaveric distal femurs (n = 5) yielding six 1.5 cm shell grafts (n = 30) were used. Three different fixation methods (2.0 and 2.4 mm headed screws, and copolymer absorbable nail) were compared for statistically significant differences (p < 0.05) in contact area, contact pressure, and shear load-to-failure. No significant differences in contact areas existed among groups (224 ± 33.5 mm2; 233.9 ± 20.8 mm2, 220.6 ± 22.7 mm2; p = 0.509 for 2.4, 2.0 mm screw, and nail, respectively). No significant differences in contact pressures existed (1.7 ± 0.6 MPa/mm2, 1.5 ± 0.8 MPa/mm2, 1.4 ± 0.9 MPa/mm2; p = 0.73 for 2.4, 2.0 mm screw, and nail, respectively). Load-to-failure for each was: 280.7 ± 48.4 N for 2.4 mm screws, 245.1 ± 70.6 N for 2.0 mm screws, and 215.2 ± 39.4 N for nails. There were no statistically significant differences in load-to-failure between 2.4 and 2.0 mm screws (p = 0.29) or between 2.0 mm screws and nails (p = 0.23); however, load-to-failure in shear was significantly higher for 2.4 mm screws compared with nails (p = 0.036). Fixation of shell OCAs using a copolymer headed nail provides initial graft-recipient compression similar to fixation using 2.0 and 2.4 mm headed screws. Nails failed in shear at significantly lower load than 2.4 mm screws but not 2.0 mm screws which have proven adequate for clinical healing. This study has clinical relevance, as a copolymer bioabsorbable headed nail (SmartNail) has graft-recipient compression and shear load-to-failure properties that suggest it is viable for shell OCA fixation.

The minipig as a potential model for pedicle screw fixation: morphometry and mechanics.

BACKGROUND: While there are several different animal models for use in the characterization of spinal fixation, none have emerged as a definitive model for comparative studies in spinal fixation methods. The purpose of this study is to establish morphometric data of porcine vertebrae and to characterize the feasibility of pedicle screw fixation in porcine spines for potential comparative human study. METHODS: Four spines from 45 to 50 kg Hanford minipigs were cleaned of soft tissue and analyzed by computed tomography and dual-energy x-ray absorptiometry. Two 5 × 30-mm pedicle screws were placed in each vertebra and tested to failure using a combined moment-load protocol. RESULTS: Pedicle widths were measured from L6-T5. Widths ranged from 7.15 mm (T6) to 9.24 mm (T14). Posterior cortex to anterior cortex depth ranged from 25.9 to 32.6 mm. Mean bone mineral density was 1.0665 g/cm2 (range 1.139-1.016). Force-to-failure demonstrated mean 1171.40 N (+ 115.34). CONCLUSION: Our baseline morphometric and compositional data demonstrate that porcine vertebrae can serve as a useful model for comparative studies due to their similar pedicle widths and bone mineral density to the human vertebra. This biomechanical data could provide a baseline comparison for future studies. This study also suggests that the minipig could be a suitable model for comparative studies due to similarities in pedicle width and bone mineral density to the human vertebrae.

A Biomechanical Study of the Role of the Anterolateral Ligament and the Deep Iliotibial Band for Control of a Simulated Pivot Shift With Comparison of Minimally Invasive Extra-articular Anterolateral Tendon Graft Reconstruction Versus Modified Lemaire Reconstruction After Anterior Cruciate Ligament Reconstruction.

PURPOSE: To determine whether the deep fibers of the iliotibial band (dITB) or the anterolateral ligament (ALL) provides more control of a simulated pivot shift and whether a minimally invasive anterolateral reconstruction (ALR) designed to functionally restore the ALL and dITB is mechanically equivalent to a modified Lemaire reconstruction (MLR). METHODS: Six matched pairs of cadaveric knees (N = 12) were subjected to a simulated pivot shift to evaluate anteroposterior translation; internal rotation; and valgus laxity at 0°, 30°, and 90° of flexion. The anterior cruciate ligament (ACL) was sectioned in all specimens, and retesting was performed. Within each pair, sequential sectioning of the ALL and dITB was performed, followed by testing; the contralateral knee was sectioned in reverse order. Knees underwent ACL reconstruction (ACLR) and repeat testing. Then, MLR (n = 6) or ALR (n = 6) was performed on matched pairs for final testing. RESULTS: Sectioning of the dITB versus ALL (after ACL sectioning) produced significantly more anterior translation at all flexion angles (P = .004, P = .012, and P = .011 for 0°, 30°, and 90°, respectively). The ACL-plus-dITB sectioned state had significantly more internal rotation at 0° versus ACL plus ALL (P = .03). ACLR plus ALR restored native anterior translation at all flexion angles. ACLR plus MLR restored anterior translation to native values only at 0° (P = .34). We found no statistically significant differences between ACLR plus ALR and ACLR plus MLR at any flexion angle for internal rotation or valgus laxity compared with the native state. CONCLUSIONS: ALR of the knee in conjunction with ACLR can return the knee to its native biomechanical state without causing overconstraint. The dITB plays a more critical role in controlling anterior translation and internal rotation at 0° than the ALL. The minimally invasive ALR was functionally equivalent to MLR for restoration of knee kinematics after ACLR. CLINICAL RELEVANCE: The dITB is more important than the ALL for control of the pivot shift. A minimally invasive extra-articular tendon allograft reconstruction was biomechanically equivalent to a modified Lemaire procedure for control of a simulated pivot shift.

Biomechanical evaluation of location and mode of failure in three screw fixations for a comminuted transforaminal sacral fracture model.

BACKGROUND: Pelvic ring-comminuted transforaminal sacral fracture injuries are rotationally and vertically unstable and have a high rate of failure. OBJECTIVE: Our study purpose was to use three-dimensional (3D) optical tracking to detect onset location of bone-implant interface failure and measure the distances and angles between screws and line of applied force for correlation to strength of pelvic fracture fixation techniques. METHODS: 3D relative motion across sacral-rami fractures and screws relative to bone was measured with an optical tracking system. Synthetic pelves were used. Comminuted transforaminal sacral-rami fractures were modelled. Each pelvis was stabilised by either (1) two iliosacral screws in S1, (2) one transsacral screw in S1 and one iliosacral screw in S1 and (3) one trans-alar screw in S1 and one iliosacral screw in S1; groups 4-6 consisted of fixation groups with addition of anterior inferior iliac pelvic external fixator. Eighteen-instrumented pelvic models with right ilium fixed simulate single-leg stance. Load was applied to centre of S1 superior endplate. Five cycles of torque was initially applied, sequentially increased until permanent deformation occurred. Five cycles of axial load compression was next applied, sequentially increased until permanent deformation occurred, followed by axial loading to catastrophic failure. A Student t test was used to determine significance (p < 0.05). RESULTS: The model, protocol and 3D optical system have the ability to locate how sub-catastrophic failures initiate. Our results indicate failure of all screw-based constructs is due to localised bone failure (screw pull-in push-out at the ipsilateral ilium-screw interface, not in sacrum); thus, no difference was observed when not supplemented with external fixation. CONCLUSION: Inclusion of external fixation improved resistance only to torsional loading. TRANSLATIONAL POTENTIAL OF THIS ARTICLE: Patients with comminuted transforaminal sacral-ipsilateral rami fractures benefit from this fixation.

Inductive co-crosslinking of cellulose nanocrystal/chitosan hydrogels for the treatment of vertebral compression fractures.

Vertebral compression fractures are a very common consequence of osteoporosis for which injection of a non-biodegradable, non-bioactive, mechanically-stiff polymer bone cement into the vertebral body is the most common treatment. Recently, there has been growing interest in using bioactive, degradable, and bone biomechanics-matching products as an alternative approach for treating these fractures. In this research, we focused on creating injectable, chitosan-based hydrogels that can convey mechanical strength similar to vertebral bone as well as possess inherent osteoinductivity. First, we investigated the effects of three different factors - 1) bioactive phosphate ionic crosslinking; 2) genipin covalent crosslinking; 3) mechanically reinforcing cellulose nanocrystal incorporation - on the material properties of chitosan-based hydrogels. Mesenchymal stem cells were then exposed to hydrogels with optimum mechanical properties and stability in order to assess the biological effects of the bioactive phosphate ionic crosslinker. Our results show that hydrogels with higher ionic and covalent crosslinking ratios supplemented with neutral cellulose nanocrystals possessed desirable compressive strength and stability. Also, the significant osteoinductivity of these composite hydrogels demonstrated their potential to function as an injectable system for the future treatment of vertebral compression fractures.

Evaluation of a Novel Degradable Synthetic Biomaterial Patch for Augmentation of Tendon Healing in a Large Animal Model.

Tendon injury is common in sports. The standard of care (SOC) for tendon repair is surgical treatment. However, restored tendons often lack complete strength and functionality, and surgical repair is often unsuccessful. This controlled laboratory study investigates the healing of an Artelon patch (AP)-augmented tendon versus tendon repair alone in a preclinical canine patellar tendon defect model. Full-thickness proximal and distal flap defects were created in the patella tendons of eight purpose-bred research mongrel dogs. Dogs were randomly allocated into either the AP-augmented repair group or the SOC group (N = 8; four knees per group). Outcomes measures included limb function and pain; range of motion (ROM) and ultrasound assessment at 2, 4, and 8 weeks; and measurements of elongation, biomechanical testing, and histology at 8 weeks. Data were compared for statistically significant differences to preoperative measures and between groups (p < 0.05). The AP group had higher limb function scores compared with the SOC group at 2, 4, and 8 weeks, with statistically significant differences observed at 2 weeks (AP: 7.1 ± 1.4, SOC: 5.5 ± 0.4, p < 0.05) and 8 weeks (AP: 9.5 ± 0.7, SOC: 7.0 ± 0.9, p < 0.05). The ROM was significantly higher for the AP group at 4 weeks (AP: 105 degrees ± 4, SOC: 89 degrees ± 5, p < 0.05). Pain scores were statistically significantly lower in the AP group at 4 (AP: 0.6 ± 0.5, SOC: 2.2 ± 0.5) and 8 weeks (p < 0.05 for both comparisons). All animals in the AP group displayed full bridging tissue at week 4, while most animals of the SOC group displayed full bridging by week 8. Minimal tendon elongation was observed in both groups. Significantly more force was required to elongate tendons in the AP group compared with the SOC group (p < 0.05). Animals with AP-augmented tendon repair show an earlier regain of function, earlier regain of range of movement, less postoperative pain, and improved tendon strength when compared with animals treated with tendon repair alone.

Biomechanical Analysis of Capsular Repair Versus Arthrex TFCC Ulnar Tunnel Repair for Triangular Fibrocartilage Complex Tears.

Background: This study compares the effectiveness of a peripheral capsular repair with a knotless arthroscopic transosseous ulnar tunnel repair (TR) in restoring distal radioulnar joint (DRUJ) stability and stiffness in the setting of a massive triangular fibrocartilage complex (TFCC) tear. Methods: Eight matched pairs of fresh-frozen cadaveric forearms were tested. Each forearm was tested in supination and pronation using 3-dimensional (3D) optical tracking devices prior to any intervention. Each specimen then underwent a diagnostic wrist arthroscopy and sectioning of the TFCC's deep and superficial fibers. All specimens were then retested to assess instability secondary to the tear. The TFCC was repaired with either a peripheral capsular repair (CR) using three 2-0 polydioxanone sutures or a transosseous ulnar TR using a 2-0 FiberWire, and then retested (statistical significance; P < .05). Results: After TFCC arthroscopic sectioning, all specimens were unstable with a significant increase in translation and a significant decrease in stiffness. TFCC repair with TR resulted in displacement and stiffness similar to the native tissue. CR specimens were found to have significantly greater displacement and significantly decreased stiffness compared with the intact state. Conclusions: Arthroscopic sectioning of the TFCC resulted in DRUJ instability, as measured by stiffness and ulnar translation. TR effectively restored DRUJ stability and demonstrated no significant difference in postoperative stiffness or maximal displacement when compared with the intact specimen in pronation and supination. This study provides biomechanical evidence that an arthroscopic ulnar tunnel technique can restore stability to the DRUJ after a massive TFCC tear.

Investigating the relationship between proteomic, compositional, and histologic biomarkers and cartilage biomechanics using artificial neural networks.

A thorough understanding of the relationship between the biological and mechanical functions of articular cartilage is necessary to develop diagnostics and treatments for arthritic diseases. A key step in developing this understanding is the establishment of models which utilize large numbers of biomarkers to create comprehensive models of the interplay between cartilage biology and biomechanics, which will more accurately demonstrate the complex etiology and progression of tissue adaptation and degradation. It is the goal of this study to demonstrate the ability of artificial neural networks (ANNs) to utilize biomarkers to create predictive models of articular cartilage biomechanics, which will provide a basis for more sophisticated research in the future. Osteochondral plugs were collected from patients undergoing total knee arthroplasty, cultured, then analyzed to collect proteomic, compositional, and histologic biomarker data. Samples were subjected to stress relaxation testing as well as computational simulations using finite element analysis (FEA) modeling and optimization to determine key mechanical properties. The acquired data was fed into an ANN to generate a model which predicts the biomechanical properties of cartilage from given biomarkers. Using all significant inputs, the developed neural network predicted the ground substance modulus with a moderate degree of accuracy, but had difficulty predicting the collagen fiber modulus and cartilage permeability. Using only clinically attainable biomarkers, the best-performing model produced comparably accurate and more consistent predictions of all three mechanical properties. These models demonstrate the potential for ANNs to be included in clinical studies of articular cartilage.

Balancing Academic Rigor and Creative Thinking: A Transformational Approach to Teaching Senior Design.

Innovation arises from creativity. "Thinking outside the box" has long been seen as a necessary precursor to innovation and invention in engineering. However, creativity is rarely part of traditional engineering curricula. In 2015, our group began to explore integrating theater-based creativity methods into bioengineering capstone design. Evaluation of student outcomes was encouraging, so we continued to develop the course in 2016 and 2017. As we worked to refine the pedagogical process, we discovered tensions (real or perceived) between providing academic rigor and allowing students to embrace their creativity; for instance, we experienced some resistance from engineering faculty and students toward adopting methods they viewed as "artsy" or lacking academic rigor. Here, we discuss the tensions we observed offer potential ways to mitigate such tensions and begin to consider how to expand on our successes.

Metabolic responses of meniscal explants to injury and inflammation ex vivo.

This study was designed to characterize metabolic responses of meniscal tissue explants to injury and inflammation. We hypothesized that impact injury and interleukin (IL-1ß) stimulation of meniscal explants would result in significant increases in matrix metalloproteinase (MMP) activity and relevant cytokine production compared to controls. Mature canine meniscal explants (n = 9/group) were randomly assigned to: (i) IL-1ß (0.1 ng/ml) treated (IL); (ii) 25% strain (25); (iii) 75% strain (75); (iv) 25% + IL-1ß (25IL); (v) 75% + IL-1ß (75IL); or (vi) 0% + no IL-1ß control (NC). Explants were impacted at 100 mm/s to 0%, 25%, or 75% strain and then cultured for 12 days with or without 0.1 ng/ml rcIL-1ß. Media were refreshed every 3 days and analyzed for MMP activity, ADAMTS-4 activity, MMP-1, MMP-2, MMP-3, GAG, NO, PGE2 , IL-6, IL-8, MCP-1, and KC concentrations. Treatment with IL-1ß alone significantly increased NO, PGE2, general MMP activity, IL-6, IL-8, KC, and MCP-1 media concentrations compared to negative controls. Impact at 75% significantly increased PGE2, IL-6, IL-8, and KC media concentrations compared to negative controls. The combination of IL-1ß and 75% strain significantly increased production of PGE2 compared to IL-1ß or 75% strain alone. Impact injury to meniscal explants ex vivo is associated with increased production of pro-inflammatory mediators and degradative enzyme activity, which are exacerbated by stimulation with IL-1ß. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2657-2663, 2018.

Subchondroplasty for the treatment of post-traumatic bone marrow lesions of the medial femoral condyle in a pre-clinical canine model.

This study characterizes long-term outcomes associated with subchondroplasty (SCP) treatment for impact-induced subchondral bone marrow lesions (BML) using a validated pre-clinical canine model. With IACUC approval, purpose-bred research hounds (n = 16) underwent arthroscopic impact injury (40N) to both medial femoral condyles. At 3 months, functional assessments, arthroscopy, and MRI were performed and knees (n = 32) were randomly assigned to SCP (3 ml fluoroscopically guided percutaneous injection of AccuFill BSM into BML bone defects) or sham injection (Control). Dogs were assessed at 3, 6, 12, and 24 months after treatment using functional assessments, radiographic evaluation, arthroscopy, and MRI. Dogs were humanely euthanatized at 3, 6, 12, or 24 months after treatment for gross, microCT, and histologic assessments. All knees had focal articular cartilage defects with associated subchondral BMLs, as well as clinical dysfunction, 3 months after injury. At the 3 and 6 months, SCP knees showed more functional impairment than Control knees, however, these differences were not statistically significant. At 1- and 2-year post-treatment, function in SCP knees was better than in Control knees with range of motion being significantly (p < 0.05) better for SCP. Radiographic, arthroscopic, MRI, gross, microCT, and histologic findings matched the functional assessments well with Control being associated with better results at the two early time points and SCP being associated with better results at 1 and 2 years. Clinical significance: SCP treatment using calcium phosphate bone void filler was associated with an initial increase in pain and dysfunction followed by symptomatic benefits for up to 2 years after treatment for post-traumatic femoral condyle BMLs in a preclinical canine model. © 2018 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:2709-2717, 2018.

Skeletal Response to Soluble Activin Receptor Type IIB in Mouse Models of Osteogenesis Imperfecta.

Osteogenesis imperfecta (OI) is a heritable connective tissue disorder primarily due to mutations in the type I collagen genes (COL1A1 and COL1A2), leading to compromised biomechanical integrity in type I collagen-containing tissues such as bone. Bone is inherently mechanosensitive and thus responds and adapts to external stimuli, such as muscle mass and contractile strength, to alter its mass and shape. Myostatin, a member of the TGF-ß superfamily, signals through activin receptor type IIB to negatively regulate muscle fiber growth. Because of the positive impact of myostatin deficiency on bone mass, we utilized a soluble activin receptor type IIB-mFc (sActRIIB-mFc) fusion protein in two molecularly distinct OI mouse models (G610C and oim) and evaluated their bone properties. Wild-type (WT), +/G610C, and oim/oim mice were treated from 2 to 4 months of age with either vehicle (Tris-buffered saline) or sActRIIB-mFc (10 mg/kg). Femurs of sActRIIB-mFc-treated mice exhibited increased trabecular bone volume regardless of genotype, whereas the cortical bone microarchitecture and biomechanical strength were only improved in WT and +/G610C mice. Dynamic histomorphometric analyses suggest the improved cortical bone geometry and biomechanical integrity reflect an anabolic effect due to increased mineral apposition and bone formation rates, whereas static histomorphometric analyses supported sActRIIB-mFc treatment also having an anti-catabolic impact with decreased osteoclast number per bone surface on trabecular bone regardless of sex and genotype. Together, our data suggest that sActRIIB-mFc may provide a new therapeutic direction to improve both bone and muscle properties in OI. © 2018 American Society for Bone and Mineral Research.

Use of a Novel Magnesium-Based Resorbable Bone Cement for Augmenting Anchor and Tendon Fixation.

The aim of this study was to assess the efficacy and safety of a novel magnesium-based resorbable bone cement (OsteoCrete, Bone Solutions Incorporated) for anchor and tendon fixation. Cadaveric humeral testing involved straight pull-to-failure of rotator cuff suture anchors; OsteoCrete was injected through one anchor, and a second anchor served as the uninjected control. Testing was conducted 15 minutes post-injection. A canine preclinical model was used to evaluate the safety of the following parameters: Rotator cuff repair: A double-row technique was used to repair transected infraspinatus tendons; OsteoCrete was injected through both anchors in one limb, and the contralateral limb served as the uninjected control. Biceps tenodesis: The transected biceps tendon was implanted into a proximal humeral socket with a transcortical button; OsteoCrete was injected into the socket of one limb, and a screw was used for final fixation in the contralateral control limb. Nondestructive biomechanical testing and histologic assessment were performed after 12 weeks. OsteoCrete-augmented anchors showed significantly higher load-to-failure compared to that with uninjected controls. In cadaveric humeri with reduced bone quality, OsteoCrete increased the mean load-to-failure by 99%. Within the preclinical model, there were no complications or statistically significant biomechanical/histologic differences between the techniques. OsteoCrete has the potential for safely providing improved suture anchor and tissue fixation in patients with poor bone or tissue quality.

Validation of the Missouri Osteochondral Allograft Preservation System for the Maintenance of Osteochondral Allograft Quality During Prolonged Storage.

BACKGROUND: Fresh osteochondral allografts (OCAs) are limited in availability. The Missouri Osteochondral Allograft Preservation System (MOPS) has been reported to effectively preserve OCAs twice as long as current tissue bank protocols in preclinical studies. HYPOTHESIS: The viable chondrocyte density (VCD) in OCAs preserved for up to 70 days using the MOPS will not be significantly different from day 0, and the VCD in MOPS-preserved OCAs will be significantly higher than for standard tissue bank preservation. Media changes during preservation will significantly improve the VCD. STUDY DESIGN: Controlled laboratory study. METHODS: Femoral condyles harvested from qualified donors (n = 12) were quartered (n = 48), assigned to 1 of 4 treatment groups (tissue bank protocol at 4°C or MOPS at 25°C, with or without media changes), and preserved for 0, 28, 56, or 70 days and assessed for the VCD and histopathological characteristics. In addition, osteochondral explants were created from the femoral condyles of 12 donors (n = 36 explants), assigned to the same groups and time points, and tested for biomechanical properties. RESULTS: MOPS-preserved OCAs maintained the day 0 VCD through 56 days. OCAs stored using current tissue bank protocols had a significantly lower VCD compared with day 0 and the MOPS by day 28. OCA histological and biomechanical properties did not significantly change from day 0 for any group. CONCLUSION: The MOPS preserved essential OCA viability and quality at significantly higher levels than current tissue bank protocols for at least 56 days after procurement. CLINICAL RELEVANCE: Improving the viability and duration of OCA preservation provides potential benefits to tissue banks, donor families, surgeons, and patients with respect to tissue use, financial costs, and outcomes.

Rotator cuff healing using demineralized cancellous bone matrix sponge interposition compared to standard repair in a preclinical canine model.

This Level II study assessed clinically relevant outcomes for repair of large, retracted infraspinatus tendons (ISTs) using a demineralized bone matrix (DBM) sponge (FlexiGraft) hydrated in platelet-rich plasma (PRP) versus direct repair in a validated canine model. Adult research dogs (n = 10) were used. The IST was transected in each shoulder (n = 20) and randomized to direct repair or repair with DBM-PRP interposition at 4 weeks posttransection. At 12 weeks postrepair, dogs were sacrificed, and the repair evaluated by magnetic resonance imaging (MRI), histology, and biomechanical testing. MRI and histology scores were significantly (p < 0.05) better in the DBM-PRP shoulders. Biomechanical testing revealed significantly improved strength of the DBM-PRP repairs at 5 and 10 mm of displacement, as well as for ultimate failure load. In this canine model of retracted IST repair, DBM-PRP sponge hydrated in PRP was considered safe and effective. In addition, use of DBM-PRP was associated with improved MRI and histologic appearance, and improved strength compared to direct repair. CLINICAL SIGNIFICANCE: Based on reported failure rates for repair of large, retracted rotator cuff tears, improving tendon-to-bone healing is critical. Use of DBM combined with PRP shows potential for addressing this critical clinical need. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:906-912, 2018.

Parametric imaging of collagen structural changes in human osteoarthritic cartilage using optical polarization tractography.

Collagen degeneration is an important pathological feature of osteoarthritis. The purpose of this study is to investigate whether the polarization-sensitive optical coherence tomography (PSOCT)-based optical polarization tractography (OPT) can be useful in imaging collagen structural changes in human osteoarthritic cartilage samples. OPT eliminated the banding artifacts in conventional PSOCT by calculating the depth-resolved local birefringence and fiber orientation. A close comparison between OPT and PSOCT showed that OPT provided improved visualization and characterization of the zonal structure in human cartilage. Experimental results obtained in this study also underlined the importance of knowing the collagen fiber orientation in conventional polarized light microscopy assessment. In addition, parametric OPT imaging was achieved by quantifying the surface roughness, birefringence, and fiber dispersion in the superficial zone of the cartilage. These quantitative parametric images provided complementary information on the structural changes in cartilage, which can be useful for a comprehensive evaluation of collagen damage in osteoarthritic cartilage.

Biologic Joint Repair Strategies: The Mizzou BioJoint Story.

Because articular cartilage has very limited healing potential, most symptomatic cartilage injuries eventually result in end-stage osteoarthritis and are treated with artificial joint replacement. Our interdisciplinary, comparative orthopedic research performed by a team of DVMs, MDs, engineers, and basic scientists has yielded marked progress toward effective biologic joint restoration strategies by bringing bench-side ideas to fruition in bedside applications in both canine and human patients. This mini-review summarizes the progress of biologic joint restoration strategies at our center.