A Narrative Review on Recombinant Human Bone Morphogenetic Protein 2: Where Are We Now?

Spinal fusion is a prevalent surgical intervention for degenerative spinal diseases, with increasing demand driven by ageing populations. The coexistence of multiple chronic conditions, termed multimorbidity, often complicates surgical outcomes, making advanced bone grafts crucial for successful fusions. This paper reviews the development, clinical application, and controversies surrounding the use of recombinant human bone morphogenetic protein-2 (rhBMP-2) in spinal fusion surgeries. A comprehensive narrative review was conducted, focusing on literature from January 1980 to January 2024, sourced from PubMed and Google Scholar. Studies included those examining rhBMP-2 specifically in spinal fusion contexts, excluding other bone morphogenetic proteins (BMPs) and non-spinal applications. This review presents an overarching synopsis of rhBMP-2, its development history and clinical efficacy, the emergence of side effects, and evolving patterns of clinical use. As discussed in this review, clinical practice has adjusted usage and dosages to mitigate adverse effects, yet the need for safer delivery mechanisms persists. rhBMP-2 remains a potent osteoinductive agent with comparable fusion success, as measured by radiographic fusion and good clinical outcomes, to autologous grafts but poses unique risks. This review sets out how further research is essential to optimise the delivery of rhBMP-2 to reduce side effects. Enhanced understanding and innovation of spatio-temporal presentation relative to endogenous BMP could significantly improve patient outcomes in spinal fusion surgeries. The review contributes to the growing body of literature on the use of rhBMP-2 in spine surgery and discusses changing patterns of clinical use over time.

In vivo Assessment of AMP2, a Novel Ceramic-Binding BMP-2, in Ovine Lumbar Interbody Fusion.

STUDY DESIGN: Assessment of bone formation in an ovine interbody fusion study. OBJECTIVE: To compare OsteoAdapt SP, which consists of AMP-2, a modified variant of recombinant human bone morphogenetic protein (rhBMP-2) bound to a tricalcium phosphate-containing carrier, to autologous iliac crest bone graft (ICBG) in a lumbar interbody fusion model. SUMMARY OF BACKGROUND DATA: Treatment of lumbar disk degeneration often involves spinal fusion to reduce pain and motion at the affected spinal segment by insertion of a cage containing bone graft material. Three graft materials were compared in this study-ICBG and OsteoAdapt SP (low or high dose). METHODS: The sheep underwent lateral lumbar fusion surgery with PEEK or Titanium interbody cages packed with OsteoAdapt SP (low or high dose) or ICBG. Outcomes were evaluated at 8-, 16- and 26- weeks. Newly formed bone quality, bone mineralization, and fusion were assessed by manual palpation, qualitative and semi-quantitative histopathology, histomorphometry, computed tomography (CT), and micro-CT (mCT) analysis. RESULTS: OsteoAdapt SP was implanted into 43 animals and ICBG into 21 animals (L3-L4). No group showed evidence of systemic toxicity by multiple assessments. All levels were fused by manual palpation at 26 weeks. Serial CT scans showed increasing fusion scores over time. Both doses of OsteoAdapt SP resulted in robust new bone formation and progression of fusion in the interbody cage. Range of motion tests for treatment groups was lower compared with ICBG at 8- and 16 weeks. Similarly, histology at eight weeks demonstrated more robust new bone formation for both OsteoAdapt SP groups compared to autograft. CONCLUSION: We have demonstrated the preclinical safety and efficacy of OsteoAdapt SP in a clinically relevant large animal model, supporting faster and more robust new bone formation within the interbody cage, comparable to or better than the gold standard, ICBG, in all measures.

Anterior cruciate ligament zoobiquity: Can man's best friend tell us we are being too cautious with the implementation of osteotomy to correct posterior tibial slope.

Anterior cruciate ligament (ACL) reconstruction (ACLR) is used to treat clinical instability post ACL rupture, however, there is a high rate of incomplete return to sport and rerupture. There is increasing interest in posterior tibial slope as an intrinsic risk factor for ACLR failure and persistent instability. Zoobiquity describes the collaboration between the human and veterinary professions in order to advance the scientific understanding of both fields. Given the cranial cruciate ligament (CCL) in dogs is synonymous with the anterior cruciate ligament in humans, functioning to control internal rotation and anterior translation, but osteotomies, rather than ligament reconstruction, are the mainstay of treatment for CCL rupture, this editorial sort to gain insights into this form of treatment from the veterinary world. Level of Evidence: Level V, evidence.

The influence of polyimide MP-1™ wear particles on a rodent closed fracture healing model.

Joint replacements provide pain free movement for the injured or our aging population. Current prothesis mainly consist of hard metal on metal, or ceramic femoral head on ultra-high-molecular weight polyethylene (UHMWPE). In this study, a rodent fracture model was used to test the influence of wear debris from a high-performance polymer (polyimide MP-1™). Saline, MP-1™ Low Dose in Saline (1%), or MP-1 High Dose (2%) in Saline was injected directly into a standard closed unilateral femoral fracture in 12-week old Sprague Dawley rats (n = 25) for 1, 3 and 6 weeks. Endpoints included radiography, micro-computed tomography, mechanical testing and paraffin histology. No adverse effects from the wear particles were observed from the current study based on radiology, mechanical or histological data. Although the particles were present, histological analysis revealed a progression in healing between the Polyimide treated groups and the non-treated saline control groups over the duration of 1, 3, and 6 weeks, with no inhibition from the particles. The MP-1™ wear debris generated are larger than 1 µm thus are not able to be engulfed by macrophages and cause osteolysis. This family of polymers (polyimides) may be an ideal material to consider for articulating joints and other implants in the human body.

Porous Cage Macro-Topography Improves Early Fusion Rates in Anterior Cervical Discectomy and Fusion.

Objectives: Anterior cervical discectomy and fusion (ACDF) aims to improve pain, relieve neural compression, achieve rapid solid bony arthrodesis, and restore cervical alignment. Bony fusion occurs as early as 3 months and up to 24 months after ACDF. The correlations between bony fusion and clinical outcomes after ACDF remain unclear. Macro-topographic and porous features have been introduced to interbody cage technology, aiming to improve the strength of the bone-implant interface to promote early fusion. In this study, we aimed to compare clinical outcomes and CT-evaluated fusion rates in patients undergoing ACDF using one of two different interbody cages: traditional NanoMetalene™ (NM) cages and NM cages with machined porous features (NMRT). Methods: This was a prospective, observational, nonrandomised, cohort study of consecutive patients undergoing ACDF. The NM cage cohort was enrolled first, then the NMRT cohort second. The visual analogue scale, neck disability index, and 12-item Short Form Survey scores were evaluated preoperatively and at 6 weeks, 3 months, and 6 months. The minimum clinical follow-up period was 12 months. Plain radiographs were obtained on postoperative day 2 to assess instrumentation positioning, and computed tomography (CT) was performed at 3 and 6 months postoperatively to assess interbody fusion (Bridwell grade). Results: Eighty-nine (52% male) patients with a mean age of 62 ± 10.5 years were included in this study. Forty-one patients received NM cages, and 48 received NMRT cages. All clinical outcomes improved significantly from baseline to 6 months. By 3 months, the NMRT group had significantly higher CT fusion rates than the NM group (79% vs 56%, p=0.02). By 6 months, there were no significant differences in fusion rates between the NMRT and NM groups (83% vs 78%, p=0.69). The mean Bridwell grade at 6 months was 1.4 ± 0.7 in the NMRT group and 1.8 ± 1.0 in the NM group (p=0.08). Conclusions: With both NM and NMRT cages, serial improvements in postoperative clinical outcomes were associated with fusion progression on CT. NMRT cages demonstrated significantly better fusion at 3 months and a trend toward higher quality of fusion at 6 months compared with NM cages, suggesting earlier cage integration with NMRT. An early 3-month postoperative CT is adequate for fusion assessment in almost 80% of patients undergoing ACDF with an NMRT cage, permitting an earlier return to activity.

Lateral fenestration of lumbar intervertebral discs in rabbits: development and characterisation of an in vivo preclinical model with multi-modal endpoint analysis.

PURPOSE: To evaluate the biological and biomechanical effects of fenestration/microdiscectomy in an in vivo rabbit model, and in doing so, create a preclinical animal model of IVDD. METHODS: Lateral lumbar IVD fenestration was performed in vivo as single- (L3/4; n = 12) and multi-level (L2/3, L3/4, L4/5; n = 12) fenestration in skeletally mature 6-month-old New Zealand White rabbits. Radiographic, micro-CT, micro-MRI, non-destructive robotic range of motion, and histological evaluations were performed 6- and 12-weeks postoperatively. Independent t tests, one-way and two-way ANOVA and Kruskal-Wallis tests were used for parametric and nonparametric data, respectively. Statistical significance was set at P < 0.05. RESULTS: All rabbits recovered uneventfully from surgery and ambulated normally. Radiographs and micro-CT demonstrated marked reactive proliferative osseous changes and endplate sclerosis at fenestrated IVDs. Range of motion at the fenestrated disc space was significantly reduced compared to intact controls at 6- and 12-weeks postoperatively (P < 0.05). Mean disc height index percentage for fenestrated IVDs was significantly lower than adjacent, non-operated IVDs for both single and multi-level groups, at 6 and 12 weeks (P < 0.001). Pfirrmann MRI IVDD and histological grading scores were significantly higher for fenestrated IVDs compared to non-operated adjacent and age-matched control IVDs for single and multi-level groups at 6 and 12 weeks (P < 0.001). CONCLUSIONS: Fenestration, akin to microdiscectomy, demonstrated significant biological, and biomechanical effects in this in vivo rabbit model and warrants consideration by veterinary and human spine surgeons. This described model may be suitable for preclinical in vivo evaluation of therapeutic strategies for IVDD in veterinary and human patients.

Telehealth through the pandemic at a safety net hospital: observations and next steps for cancer care delivery.

The COVID-19 pandemic revolutionized cancer care delivery leading to rapid adoption of digital technology for telehealth in the United States. In this study, we describe telehealth utilization trends across the three largest waves of the pandemic at a safety net academic center. We also provide a perspective on lessons learnt and our vision for cancer care delivery using digital technology in the near future. The integration of interpreter services within the video platform and its integration within the electronic medical record system is crucial for safety net institutes that service a diverse patient population. Pay-parity for telehealth, especially ongoing support for audio-only visits, will be critical in overcoming health disparities for patients without access to smartphone technology. Use of telehealth in clinical trials, widespread adoption of hospital at home programs, electronic consults for rapid access, and structured telehealth slots in clinic templates will be crucial in making cancer care more equitable and efficient.

Knotless Tendon Repair with a Resorbable Barbed Suture: An In-vivo Comparison in the Turkey Foot.

Background: Un-knotted barbed suture constructs are postulated to decrease repair bulk and improve tension loading along the entire repair site resulting in beneficial biomechanical repair properties. Applying this repair technique to tendons has shown good results in ex-vivo experiments previously but thus far no in-vivo study could confirm these. Therefore, this current study was conducted to assess the value of un-knotted barbed suture repairs in the primary repair of flexor tendons in an in-vivo setting. Methods: Two groups of 10 turkeys (Meleagris gallapovos) were used. All turkeys underwent surgical zone II flexor tendon laceration repairs. In group one, tendons were repaired using a traditional four-strand cross-locked cruciate (Adelaide) repair, while in group two, a four-strand knotless barbed suture 3D repair was used. Postoperatively repaired digits were casted in functional position, and animals were left free to mobilise and full weight bear, resembling a high-tension post-op rehabilitation protocol. Surgeries and rehabilitations went uneventful and no major complications were noted. The turkeys were monitored for 6 weeks before the repairs were re-examined and assessed against several outcomes, such as failure rate, repair bulk, range of motion, adhesion formation and biomechanical stability. Results: In this high-tension in-vivo tendon repair experiment, traditionally repaired tendons performed significantly better when comparing absolute failure rates and repair stability after 6 weeks. Nevertheless, the knotless barbed suture repairs that remained intact demonstrated benefits in all other outcome measures, including repair bulk, range of motion, adhesion formation and operating time. Conclusions: Previously demonstrated ex-vivo benefits of flexor tendon repairs with resorbable barbed sutures may not be applicable in an in-vivo setting due to significant difference in repair stability and failure rates. Level of Evidence: Level IV (Therapeutic).

Preclinical in vivo animal models of intervertebral disc degeneration. Part 1: A systematic review.

Intervertebral disc degeneration (IVDD), a widely recognized cause of lower back pain, is the leading cause of disability worldwide. A myriad of preclinical in vivo animal models of IVDD have been described in the literature. There is a need for critical evaluation of these models to better inform researchers and clinicians to optimize study design and ultimately, enhance experimental outcomes. The purpose of this study was to conduct an extensive systematic literature review to report the variability of animal species, IVDD induction method, and experimental timepoints and endpoints used in in vivo IVDD preclinical research. A systematic literature review of peer-reviewed manuscripts featured on PubMed and EMBASE databases was conducted in accordance with PRISMA guidelines. Studies were included if they reported an in vivo animal model of IVDD and included details of the species used, how disc degeneration was induced, and the experimental endpoints used for analysis. Two-hundred and fifty-nine (259) studies were reviewed. The most common species, IVDD induction method and experimental endpoint used was rodents(140/259, 54.05%), surgery (168/259, 64.86%) and histology (217/259, 83.78%), respectively. Experimental timepoint varied greatly between studies, ranging from 1 week (dog and rodent models), to >104 weeks in dog, horse, monkey, rabbit, and sheep models. The two most common timepoints used across all species were 4 weeks (49 manuscripts) and 12 weeks (44 manuscripts). A comprehensive discussion of the species, methods of IVDD induction and experimental endpoints is presented. There was great variability across all categories: animal species, method of IVDD induction, timepoints and experimental endpoints. While no animal model can replicate the human scenario, the most appropriate model should be selected in line with the study objectives to optimize experimental design, outcomes and improve comparisons between studies.

Anatomy of the distal radioulnar ligament in cats.

OBJECTIVES: The aim of this study was to describe the anatomy of the distal radioulnar ligament in the cat, using gross and histological sections from cadaveric feline carpi. METHODS: Eight feline cadaveric distal radioulnar joints were included in the study, including six that were paraffin- and two that were polymethyl methacrylate-embedded. Each of the sections of the distal radioulnar joint and ligament were viewed macroscopically and microscopically using a dissection microscope and a standard light microscope with polarising capacity. RESULTS: On gross examination, the distal radioulnar ligament could be seen as a triangular-shaped structure extending between the dorsal surface of the distal radius and ulna. The centre of the ligament had a greater density of tightly packed collagen fibres, while fibrocartilage was identified at the site of both the radial and ulnar entheses. Articular cartilage was noted to extend to the most proximal part of the bulbous portion of the distal ulna and corresponding axial aspect of the distal radius. CONCLUSIONS AND RELEVANCE: In the cat, there appears to be a less extensive interosseous component of the distal radioulnar ligament compared with the dog and cheetah. Instead, the ligament follows the articular surfaces of the distal radius and ulna. These anatomical differences may account for increased rotation of the feline antebrachium and have clinical implications, particularly with regard to the management of antebrachiocarpal joint injuries.

Cyclic Testing of a Modified Pull-Out Suture Repair Technique for Flexor Digitorum Profundus Avulsion in a Turkey Foot Model.

Background: Numerous repair techniques have been described for closed flexor digitorum profundus (FDP) avulsion. One option is a pull-out suture tied over the nail plate (Bunnell repair). We modified the Bunnell repair by incorporating a portion of the distal interphalangeal (DIP) joint volar plate into the repair to improve strength and reduce gapping. The aim of this study is to compare gap formation and load to failure between the Bunnell repair and our modification in a turkey foot model. Methods: Twenty-four fresh-frozen cadaveric turkey feet were divided into two repair groups namely the conventional Bunnell pull-out suture technique and the modified Bunnell pull-out suture technique, incorporating the middle-third of the DIP joint volar plate into the repair. Both repairs were carried out with 3-0 prolene suture and underwent ex-vivo cyclic loading at 2-12 n in a sinusoidal wave for 100 cycles to simulate a passive range of motion (ROM) protocol. Subsequently, specimens were loaded to failure at 12 mm/minute. Gap formation and load to failure were measured. Results: No repair ruptures occurred during cyclical testing. Mean gap formation was 9.2 mm (±1.49) in the Bunnell repair, and 3.5 mm (±1.19) in the modified Bunnell repair (p < 0.0001). The mean load to failure for the Bunnell repair was 35.4 n compared to 45 n for the modified repair (p = 0.0017). Conclusions: Gap formation was reduced and load to failure increased by augmenting the Bunnell pull-out suture repair with the central portion of the DIP joint volar plate.

Characterization of costal cartilage allografts.

BACKGROUND: Human costal cartilage remains widely used in the reconstruction of soft tissues, particularly within the field of plastic and orthopaedic surgery. The biologic expense of using autologous human costal cartilage has become superseded by the increasingly common use of irradiated costal cartilage allografts. To date, there has been no histologic investigation of such costal cartilage allografts. This study aims to characterize the histologic variations that exist between different costal cartilage specimens, and to quantify this between specimens in spite of their common anatomical derivation. METHODS: Twenty-five specimens of cadaveric human costal cartilage were obtained from Australian Biotechnologies. Each specimen was irradiated, sectioned and stained with Haematoxylin and Eosin, Masson's trichrome and tetrachrome stains. After being analysed under light microscopy, specimen dimensions, chondrocyte counts and mineral content was quantified and measured. RESULTS: The median specimen diameter was 8.20 mm, with an interquartile range (IQR) of 1.59 mm. The median measurement from the superficial to basal chondrocyte layer was 1409.91 µm (IQR = 885.59 µm), and the median measurement from superficial to calcified zone was 4146.26 µm (IQR 1441.83 µm). The median chondrocyte area was 442.74 µm2 (IQR = 2622.72 µm2 ) with their total chondrocyte count ranging from 289 to 591 chondrocytes per square millimetre. The median percentages of collagen and mineral content were 45.17% and 71.82%, respectively (IQR = 20.48%, 14.75%). CONCLUSION: These findings emphasize the histologic and biochemical degree of variation that exists between specimens of human cadaveric costal cartilage on a microscopic level. This has the potential to influence the selection of costal cartilage allografts for reconstructive purposes.

Mesoderm-derived PDGFRA+ cells regulate the emergence of hematopoietic stem cells in the dorsal aorta.

Mouse haematopoietic stem cells (HSCs) first emerge at embryonic day 10.5 (E10.5), on the ventral surface of the dorsal aorta, by endothelial-to-haematopoietic transition. We investigated whether mesenchymal stem cells, which provide an essential niche for long-term HSCs (LT-HSCs) in the bone marrow, reside in the aorta-gonad-mesonephros and contribute to the development of the dorsal aorta and endothelial-to-haematopoietic transition. Here we show that mesoderm-derived PDGFRA+ stromal cells (Mesp1der PSCs) contribute to the haemogenic endothelium of the dorsal aorta and populate the E10.5-E11.5 aorta-gonad-mesonephros but by E13.5 were replaced by neural-crest-derived PSCs (Wnt1der PSCs). Co-aggregating non-haemogenic endothelial cells with Mesp1der PSCs but not Wnt1der PSCs resulted in activation of a haematopoietic transcriptional programme in endothelial cells and generation of LT-HSCs. Dose-dependent inhibition of PDGFRA or BMP, WNT and NOTCH signalling interrupted this reprogramming event. Together, aorta-gonad-mesonephros Mesp1der PSCs could potentially be harnessed to manufacture LT-HSCs from endothelium.

'SMART' implantable devices for spinal implants: a systematic review on current and future trends.

Background: 'SMART' implants refer to modified orthopedic implants that combine the biomechanical safety and efficacy of traditional devices with the intelligence of data-logging sensors. This review aims to systematically assess the available literature on SMART spinal implants and present these findings in a clinically relevant manner. Methods: A search of PubMed, Scopus, and Google Scholar databases was conducted by two separate reviewers. Information including sensor type, intended application, and sample size, was extracted from included studies. Risk of bias assessment was conducted using the Office of Health Assessment and Translation (OHAT) risk of bias tool. Results: Eighteen studies were included for analysis. Eight studies involved SMART rods and ten studies used SMART vertebral body replacements (VBR). No more than 20 patients are reported to have received a SMART spinal implant. Including non-primary evidence, seven unique designs for SMART spinal implants were found. The majority of these used strain gauges with recent designs including thermometers and accelerometers. Discussion: At present, SMART spinal implants have primarily focused on utilising strain gauges to report loading on the implant itself. This is a logical first step as it allows quantification of real-world requirements of an implant, detection of catastrophic failure, while also allowing researchers and clinicians to estimate changes in load sharing between newly forming bone and the implant itself, providing real-time information on the progression of healing and fusion. Future work includes documenting the correlation between data provided by these SMART implants and clinical findings, including complications such as pedicle screw loosening and interbody cage subsidence.

Validation of a novel range of motion assessment tool for the cervical spine: the HALO© digital goniometer.

Background: Cervical spine range of motion (ROM) assessment has long been carried out via use of the universal goniometer (UG) as an objective tool in the evaluation of patient rehabilitation pre- and post-operatively. The advent of novel ROM assessment technology, such as HALO digital goniometer (DG), presents an avenue for research and potential application within clinical and surgical settings. The objective of this study was to examine the reliability and validity of the HALO DG in the assessment of the active ROM of the cervical spine. Methods: One hundred healthy subjects were recruited for the study and were split into two groups to be assessed by either physiotherapists or medical students. The methodology for cervical spine ROM assessment was carried out per the American Association of Orthopaedic Surgeons (AAOS) guidelines. The reliability analysis was completed using IBM SPSS Statistics 25, calculating the intraclass correlation coefficients (ICC) to determine both the intra- and inter-rater reliability of the device. Results: Inter-rater reliability within the physiotherapist cohort with the DG (ICCr =0.477, 0.718, 0.551) was higher compared to the UG (ICCr =0.380, 0.510, 0.255) for active cervical flexion, lateral flexion, and rotation, respectively. The UG (ICCr =0.819) showed better reliability versus the DG (ICCr =0.780) when assessing cervical extension. Similarly, in the medical student cohort, the DG outperformed the UG in all movement except cervical lateral flexion. When assessing for intra-rater reliability, the DG (ICCm =0.507, 0.773, 0.728, 0.691) performed better than the UG (ICCm =0.487, 0.529, 0.532, 0.585) in cervical flexion, extension, lateral flexion, and rotation, respectively. Conclusions: The present validation study identified the DG as a reliable substitute for the UG.

Standalone titanium/polyetheretherketone interbody cage for anterior lumbar interbody fusion: Clinical and radiological results at 24 months.

Context: Anterior lumbar interbody fusion (ALIF) is a common procedure for patients suffering degenerative, deformity, or posttraumatic pathologies of the lumbar spine. Aims: The aim of this study is to evaluate the clinical and radiological outcomes of a combination Titanium/Polyetheretherketone (Ti/PEEK) 3-screw fixation ALIF cage. Settings and Design: This was a prospective multisurgeon series of 87 patients (105 implants), with a minimum 24-month follow-up. Twelve patients (12/87) were supplemented with posterior percutaneous pedicle screw fixation for additional stability for pars defect spondylolisthesis correction. Radiological follow-up with fine-cut computed tomography (CT) scan occurred at 4-6 months, and again at 18-24 months if no fusion observed on initial CT, was performed to evaluate early and final fusion rates, and integration of the Ti/PEEK cage at the end-plate junction. Clinical follow-up included the subjective measures of pain and functional status and objective wearable device monitoring. Results: The fusion rate was 85% (97/105 implants) 6 months postoperatively, with no implant-related complications, and 95% at 24 months, based on independent radiological assessment. Patients experienced statistically significant improvement in subjective pain and functional outcomes compared to preoperative status. The objective measures revealed a daily step count with a 27% improvement, and gait velocity with a mean increase from 0.97 m/s to 1.18 m/s, at 3 months postoperatively. Conclusions: A Ti/PEEK cage, with allograft and bone morphogenetic protein-2 (BMP-2), achieved rapid interbody progression to fusion and is an effective implant for use in anterior lumbar surgery with high early fusion rates and no peri-endplate lucency. Supercritical CO2 allograft provided an osteoconductive scaffold and combined well with BMP-2 to facilitate fusion.

Physico-Chemical Characteristics and Posterolateral Fusion Performance of Biphasic Calcium Phosphate with Submicron Needle-Shaped Surface Topography Combined with a Novel Polymer Binder.

A biphasic calcium phosphate with submicron needle-shaped surface topography combined with a novel polyethylene glycol/polylactic acid triblock copolymer binder (BCP-EP) was investigated in this study. This study aims to evaluate the composition, degradation mechanism and bioactivity of BCP-EP in vitro, and its in vivo performance as an autograft bone graft (ABG) extender in a rabbit Posterolateral Fusion (PLF) model. The characterization of BCP-EP and its in vitro degradation products showed that the binder hydrolyses rapidly into lactic acid, lactide oligomers and unaltered PEG (polyethylene glycol) without altering the BCP granules and their characteristic submicron needle-shaped surface topography. The bioactivity of BCP-EP after immersion in SBF revealed a progressive surface mineralization. In vivo, BCP-EP was assessed in a rabbit PLF model by radiography, manual palpation, histology and histomorphometry up to 12 weeks post-implantation. Twenty skeletally mature New Zealand (NZ) White Rabbits underwent single-level intertransverse process PLF surgery at L4/5 using (1) autologous bone graft (ABG) alone or (2) by mixing in a 1:1 ratio with BCP-EP (BCP-EP/ABG). After 3 days of implantation, histology showed the BCP granules were in direct contact with tissues and cells. After 12 weeks, material resorption and mature bone formation were observed, which resulted in solid fusion between the two transverse processes, following all assessment methods. BCP-EP/ABG showed comparable fusion rates with ABG at 12 weeks, and no graft migration or adverse reaction were noted at the implantation site nor in distant organs.

Historical Note: The Evolution of Cortical Bone Trajectory and Associated Techniques.

Cortical bone trajectory (CBT) for posterior fixation with pedicle screws is considered a relatively new alternative trajectory that travels in the medio-lateral direction in the transverse plane and in the caudo-cephalad path in the sagittal plane. Various biomechanical studies have already validated its superior pullout strength and mechanical stability over the traditional trajectory of convergent pedicle screws. Due to the relatively medial starting point of this trajectory, the CBT also poses the clinical advantage of requiring a smaller surgical field of exposure, thus minimizing tissue and muscle injury while reducing operative time and intraoperative blood loss. The evolution of CBT through time has closely been linked to the unwavering philosophy of prioritizing patient outcomes, advancements in neuronavigational technology, and the mounting biomechanical, morphometric, and clinical evidence. In this historical review, we provide a unique perspective on how CBT surgical technique has developed through time, highlighting key milestones and attempting to explain its explosive rise in popularity.

Subsidence and fusion performance of a 3D-printed porous interbody cage with stress-optimized body lattice and microporous endplates - a comprehensive mechanical and biological analysis.

BACKGROUND CONTEXT: Cage subsidence remains a serious complication after spinal fusion surgery. Novel porous designs in the cage body or endplate offer attractive options to improve subsidence and osseointegration performance. PURPOSE: To elucidate the relative contribution of a porous design in each of the two major domains (body and endplates) to cage stiffness and subsidence performance, using standardized mechanical testing methods, and to analyze the fusion progression via an established ovine interbody fusion model to support the mechanical testing findings. STUDY DESIGN/SETTING: A comparative preclinical study using standardized mechanical testing and established animal model. METHODS: To isolate the subsidence performance contributed by each porous cage design feature, namely the stress-optimized body lattice (vs. a solid body) and microporous endplates (vs. smooth endplates), four groups of cages (two-by-two combination of these two features) were tested in: (1) static axial compression of the cage (per ASTM F2077) and (2) static subsidence (per ASTM F2267). To evaluate the progression of fusion, titanium cages were created with a microporous endplate and internal lattice architecture analogous to commercial implants used in subsidence testing and implanted in an endplate-sparing, ovine intervertebral body fusion model. RESULTS: The cage stiffness was reduced by 16.7% by the porous body lattice, and by 16.6% by the microporous endplates. The porous titanium cage with both porous features showed the lowest stiffness with a value of 40.4±0.3 kN/mm (Mean±SEM) and a block stiffness of 1976.8±27.4 N/mm for subsidence. The body lattice showed no significant impact on the block stiffness (1.4% reduction), while the microporous endplates decreased the block stiffness significantly by 24.9% (p<.0001). All segments implanted with porous titanium cages were deemed rigidly fused by manual palpation, except one at 12 weeks, consistent with robotic ROM testing and radiographic and histologic observations. A reduction in ROM was noted from 12 to 26 weeks (4.1±1.6° to 2.2±1.4° in lateral bending, p<.05; 2.1±0.6° to 1.5±0.3° in axial rotation, p<.05); and 3.3±1.6° to 1.9±1.2° in flexion extension, p=.07). Bone in the available void improved with time in the central aperture (54±35% to 83±13%, p<.05) and porous cage structure (19±26% to 37±21%, p=.15). CONCLUSIONS: Body lattice and microporous endplates features can effectively reduce the cage stiffness, therefore reducing the risk of stress shielding and promoting early fusion. While body lattice showed no impact on block stiffness and the microporous endplates reduced the block stiffness, a titanium cage with microporous endplates and internal lattice supported bone ingrowth and segmental mechanical stability as early as 12 weeks in ovine interbody fusion. CLINICAL SIGNIFICANCE: Porous titanium cage architecture can offer an attractive solution to increase the available space for bone ingrowth and bridging to support successful spinal fusion while mitigating risks of increased subsidence.