Christopher D. Lopez

Osseodensification for enhancement of spinal surgical hardware fixation

Integration between implant and bone is an essential concept for osseous healing requiring hardware placement. A novel approach to hardware implantation, termed osseodensification, is described here as an effective alternative. 12 sheep averaging 65kg had fixation devices installed in their C2, C3, and C4 vertebral bodies; each device measured 4mm diameter×10mm length. The left-sided vertebral body devices were implanted using regular surgical drilling (R) while the right-sided devices were implanted using osseodensification drilling (OD). The C2 and C4 vertebra provided the t=0 in vivo time point, while the C3 vertebra provided the t=3 and t=6 week time points, in vivo. Structural competence of hardware was measured using biomechanical testing of pullout strength, while the quality and degree of new bone formation and remodeling was assessed via histomorphometry. Pullout strength demonstrated osseodensification drilling to provide superior anchoring when compared to the control group collapsed over time with statistical significance (p<0.01). On Wilcoxon rank signed test, C2 and C4 specimens demonstrated significance when comparing device pullout (p=0.031) for both, and C3 pullout tests at 3 and 6 weeks collapsed over time had significance as well (p=0.027). Percent bone-to-implant contact (%BIC) analysis as a function of drilling technique demonstrated an OD group with significantly higher values relative to the R group (p<0.01). Similarly, percent bone-area-fraction-occupancy (BAFO) analysis presented with significantly higher values for the OD group compared to the R group (p=0.024). As a function of time, between 0 and 3 weeks, a decrease in BAFO was observed, a trend that reversed between 3 and 6 weeks, resulting in a BAFO value roughly equivalent to the t=0 percentage, which was attributed to an initial loss of bone fraction due to remodeling, followed by regaining of bone fraction via production of woven bone. Histomorphological data demonstrated autologous bone chips in the OD group with greater frequency relative to the control, which acted as nucleating surfaces promoting new bone formation around the implants, providing superior stability and greater bone density. This alternative approach to a critical component of hardware implantation encourages assessment of current surgical approaches to hardware implantation.

Three dimensionally printed bioactive ceramic scaffold osseoconduction across critical-sized mandibular defects

BACKGROUNDnVascularized bone tissue transfer, commonly used to reconstruct large mandibular defects, is challenged by long operative times, extended hospital stay, donor-site morbidity, and resulting health care. 3D-printed osseoconductive tissue-engineered scaffolds may provide an alternative solution for reconstruction of significant mandibular defects. This pilot study presents a novel 3D-printed bioactive ceramic scaffold with osseoconductive properties to treat segmental mandibular defects in a rabbit model.nnnMETHODSnFull-thickness mandibulectomy defects (12xa0mm) were created at the mandibular body of eight adult rabbits and replaced by 3D-printed ceramic scaffold made of 100% β-tricalcium phosphate, fit to defect based on computed tomography imaging. After 8 weeks, animals were euthanized, the mandibles were retrieved, and bone regeneration was assessed. Bone growth was qualitatively assessed with histology and backscatter scanning electron microscopy, quantified both histologically and with micro computed tomography and advanced 3D image reconstruction software, and compared to unoperated mandible sections (UMSs).nnnRESULTSnHistology quantified scaffold with newly formed bone area occupancy at 54.3xa0±xa011.7%, compared to UMS baseline bone area occupancy at 55.8xa0±xa04.4%, and bone area occupancy as a function of scaffold free space at 52.8xa0±xa013.9%. 3D volume occupancy quantified newly formed bone volume occupancy was 36.3xa0±xa05.9%, compared to UMS baseline bone volume occupancy at 33.4xa0±xa03.8%, and bone volume occupancy as a function of scaffold free space at 38.0xa0±xa015.4%.nnnCONCLUSIONSn3D-printed bioactive ceramic scaffolds can restore critical mandibular segmental defects to levels similar to native bone after 8xa0weeks in an adult rabbit, critical sized, mandibular defect model.

Dipyridamole enhances osteogenesis of three-dimensionally printed bioactive ceramic scaffolds in calvarial defects

PURPOSEnThe objective of this study was to test the osteogenic capacity of dipyridamole-loaded, three-dimensionally printed, bioactive ceramic (3DPBC) scaffolds using a translational, skeletally mature, large-animal calvarial defect model.nnnMATERIALS AND METHODSnCustom 3DPBC scaffolds designed to present lattice-based porosity only towards the dural surface were either coated with collagen (control) or coated with collagen and immersed in a 100xa0μM concentration dipyridamole (DIPY) solution. Sheep (nxa0=xa05) were subjected to 2 ipsilateral trephine-induced (11-mm diameter) calvarial defects. Either a control or a DIPY scaffold was placed in each defect, and the surgery was repeated on the contralateral side 3 weeks later. Following sacrifice, defects were evaluated through microcomputed tomography and histologic analysis for bone, scaffold, and soft tissue quantification throughout the defect. Parametric and non-parametric methods were used to determine statistical significance based on data distribution.nnnRESULTSnNo exuberant or ectopic bone formation was observed, and no histologic evidence of inflammation was noted within the defects. Osteogenesis was higher in DIPY-coated scaffolds compared to controls at 3 weeks (pxa0=xa00.013) and 6 weeks (pxa0=xa00.046) inxa0vivo. When bone formation was evaluated as a function of defect radius, average bone formation was higher for DIPY relative to control scaffolds at both time points (significant at defect central regions at 3 weeks and at margins at 6 weeks, pxa0=xa00.046 and pxa0=xa00.031, respectively).nnnCONCLUSIONnDipyridamole significantly improves the calvarial bone regeneration capacity of 3DPBC scaffolds. The most significant difference in bone regeneration was observed centrally within the interface between the 3DPBC scaffold and the dura mater.

The role of 3D printing in treating craniomaxillofacial congenital anomalies

Craniomaxillofacial congenital anomalies comprise approximately one third of all congenital birth defects and include deformities such as alveolar clefts, craniosynostosis, and microtia. Current surgical treatments commonly require the use of autogenous graft material which are difficult to shape, limited in supply, associated with donor site morbidity and cannot grow with a maturing skeleton. Our group has demonstrated that 3D printed bio‐ceramic scaffolds can generate vascularized bone within large, critical‐sized defects (defects too large to heal spontaneously) of the craniomaxillofacial skeleton. Furthermore, these scaffolds are also able to function as a delivery vehicle for a new osteogenic agent with a well‐established safety profile. The same 3D printers and imaging software platforms have been leveraged by our team to create sterilizable patient‐specific intraoperative models for craniofacial reconstruction. For microtia repair, the current standard of care surgical guide is a two‐dimensional drawing taken from the contralateral ear. Our laboratory has used 3D printers and open source software platforms to design personalized microtia surgical models. In this review, we report on the advancements in tissue engineering principles, digital imaging software platforms and 3D printing that have culminated in the application of this technology to repair large bone defects in skeletally immature transitional models and provide in‐house manufactured, sterilizable patient‐specific models for craniofacial reconstruction.

Form and functional repair of long bone using 3D-printed bioactive scaffolds

Injuries to the extremities often require resection of necrotic hard tissue. For large‐bone defects, autogenous bone grafting is ideal but, similar to all grafting procedures, is subject to limitations. Synthetic biomaterial‐driven engineered healing offers an alternative approach. This work focuses on three‐dimensional (3D) printing technology of solid‐free form fabrication, more specifically robocasting/direct write. The research hypothesizes that a bioactive calcium‐phosphate scaffold may successfully regenerate extensive bony defects in vivo and that newly regenerated bone will demonstrate mechanical properties similar to native bone as healing time elapses. Robocasting technology was used in designing and printing customizable scaffolds, composed of 100% beta tri‐calcium phosphate (β‐TCP), which were used to repair critical sized long‐bone defects. Following full thickness segmental defects (~11 mm × full thickness) in the radial diaphysis in New Zealand white rabbits, a custom 3D‐printed, 100% β‐TCP, scaffold was implanted or left empty (negative control) and allowed to heal over 8, 12, and 24 weeks. Scaffolds and bone, en bloc, were subjected to micro‐CT and histological analysis for quantification of bone, scaffold and soft tissue expressed as a function of volume percentage. Additionally, biomechanical testing at two different regions, (a) bone in the scaffold and (b) in native radial bone (control), was conducted to assess the newly regenerated bone for reduced elastic modulus (Er) and hardness (H) using nanoindentation. Histological analysis showed no signs of any adverse immune response while revealing progressive remodelling of bone within the scaffold along with gradual decrease in 3D‐scaffold volume over time. Micro‐CT images indicated directional bone ingrowth, with an increase in bone formation over time. Reduced elastic modulus (Er) data for the newly regenerated bone presented statistically homogenous values analogous to native bone at the three time points, whereas hardness (H) values were equivalent to the native radial bone only at 24 weeks. The negative control samples showed limited healing at 8 weeks. Custom engineered β‐TCP scaffolds are biocompatible, resorbable, and can directionally regenerate and remodel bone in a segmental long‐bone defect in a rabbit model. Custom designs and fabrication of β‐TCP scaffolds for use in other bone defect models warrant further investigation.

Atemporal osseointegration: Early biomechanical stability through osseodensification: EARLY BIOMECHANICAL STABILITY

Osseointegration, the direct functional and structural connection between device and bone is influenced by multiple factors such as implant macrogeometry and surgical technique. This study investigated the effects of osseodensification drilling techniques on implant stability and osseointegration using trabecular metal (TM) and tapered‐screw vent (TSV) implants in a low‐density bone. Six skeletally mature sheep were used where six osteotomy sites were prepared in each of the ilia, (nu2009=u20092/technique: Regular [R] (subtractive), clockwise [CW], and counterclockwise [CCW]). One TM and one TSV implant was subsequently placed with R osteotomy sites prepared using a conventional (subtractive) drilling protocol as recommended by the implant manufacturer for low density bone. CW and CCW drilling sites were subjected to osseodensification (OD) (additive) drilling. Evaluation of insertion torque as a function of drilling technique showed implants subjected to R drilling yielded a significant lower insertion torque relative to samples implanted in OD (CW/CCW) sites (pu2009<u20090.05). Histomorphometric analysis shows that the osseodensification demonstrates significantly greater values for bone‐to‐implant contact (BIC) and bone area fraction occupancy (BAFO). Histological analysis shows the presence of bone remnants, which acted as nucleating surfaces for osteoblastic bone deposition, facilitating the bridging of bone between the surrounding native bone and implant surface, as well as within the open spaces of the trabecular network in the TM implants. Devices that were implanted via OD demonstrated atemporal biomechanical stability and osseointegration.

The effect of osseodensification drilling for endosteal implants with different surface treatments: A study in sheep: OSSEODENSIFICATION OF ENDOSTEAL IMPLANTS

This study investigated the effects of osseodensification drilling on the stability and osseointegration of machine-cut and acid-etched endosteal implants in low-density bone. Twelve sheep received six implants inserted into the ilium, bilaterally (nu2009=u200936 acid-etched, and nu2009=u200936 as-machined). Individual animals received three implants of each surface, placed via different surgical techniques: (1) subtractive regular-drilling (R): 2.0 mm pilot, 3.2 and 3.8 mm twist drills); (2) osseodensification clockwise-drilling (CW): Densah Bur (Versah, Jackson, MI) 2.0 mm pilot, 2.8, and 3.8 mm multifluted tapered burs; and (3) osseodensification counterclockwise-drilling (CCW) Densah Bur 2.0 mm pilot, 2.8 mm, and 3.8 mm multifluted tapered burs. Insertion torque was higher in the CCW and CW-drilling compared to the R-drilling (pu2009<u20090.001). Bone-to-implant contact (BIC) was significantly higher for CW (pu2009=u20090.024) and CCW-drilling (pu2009=u20090.006) compared to the R-drilling technique. For CCW-osseodensification-drilling, no statistical difference between the acid-etched and machine-cut implants at both time points was observed for BIC and BAFO (bone-area-fraction-occupancy). Resorbed bone and bone forming precursors, preosteoblasts, were observed at 3-weeks. At 12-weeks, new bone formation was observed in all groups extending to the trabecular region. In low-density bone, endosteal implants inserted via osseodensification-drilling presented higher stability and no osseointegration impairments compared to subtractive regular-drilling technique, regardless of evaluation time or implant surface.

The Role of Adenosine Receptor Activation in Attenuating Cartilaginous Inflammation

Adenosine receptor activation has been explored as a modulator of the inflammatory process that propagates osteoarthritis. It has been reported that cartilage has enhanced regenerative potential when influenced by adenosine receptor activation. As adenosine’s role in maintaining chondrocyte homeostasis at the cellular and molecular levels is explored, successful in vivo applications of adenosine delivery for cartilage repair continue to be reported. This review summarizes the role adenosine receptor ligation plays in chondrocyte homeostasis and regeneration of articular cartilage damaged in osteoarthritis. It also reports on all the modalities reported for delivery of adenosine through in vivo applications.

Local delivery of adenosine receptor agonists to promote bone regeneration and defect healing

Adenosine receptor activation has been investigated as a potential therapeutic approach to heal bone. Bone has enhanced regenerative potential when influenced by either direct or indirect adenosine receptor agonism. As investigators continue to elucidate how adenosine influences bone cell homeostasis at the cellular and molecular levels, a small but growing body of literature has reported successful in vivo applications of adenosine delivery. This review summarizes the role adenosine receptor ligation plays in osteoblast and osteoclast biology and remodeling/regeneration. It also reports on all the modalities described in the literature at this point for delivery of adenosine through in vivo models for bone healing and regeneration.

Abstract 47. Dipyridamole-Containing 3D-Printed Bioactive Ceramic Scaffolds for the Treatment of Calvarial Defects: An Experimental Study in Sheep

T ueday, M arch 8, 2017 METHODS: One hundred fifty-eight patients with 277 expanded skin cases during 2010 to 2014 were reviewed and photograph-evaluated for the expanded skin texture and regenerative condition. Overall texture of the expanded skin flaps (Good, Fair, Poor) were evaluated and documented by senior attending surgeons. The occurrence of five indications of skin regeneration limitation, including skin thickness, skin color, stretch mark, vessel varicose and skin lesion, during skin expansion were recorded. The correlation of indications to overall skin regeneration condition was statistically analyzed.