Faculty Bibliography
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248
Journal of biomedical materials research. Part B, Applied biomaterials. 2021:109(12):2237-2245.DOI: 10.1002/jbm.b.34885
Effects of relative centrifugation force on L-PRF: An in vivo submandibular boney defect regeneration study
Properties and composition of leukocyte- and platelet-rich fibrin (L-PRF) clots may be largely affected by centrifugation protocols (function of relative centrifugal force [RCF]), which may impact biological potential repair in bone regeneration. The present in vivo study sought to assess the effect of the RCF on the composition of L-PRF clots, as well as to compare the repair potential of L-PRF clots obtained with different RCF protocols in submandibular boney defects using PLGA scaffolds for bone regeneration. Complete blood count and volumetric evaluations were performed on L-PRF clots obtained through centrifugation for 12 min at 200, 400, and 600 RCF-clot centrifugation speeds. These evaluations were completed from blood collected immediately prior to any surgical procedures. The in vivo portion comprised of three submandibular unilateral, full thickness, osteotomies (~0.40cm3 ) which were created in the submandibular region of six sheep, using rotary instrumentation under continuous irrigation. Subsequently, poly(lactic-co-glycolic acid) (PLGA) scaffolds were enveloped in a L-PRF membrane from one of the three spinning speeds (n = 6/RCF) and inserted into the defect (sites were interpolated to avoid site bias). Six-weeks after surgery, the mandibles were harvested en bloc and prepared for volumetric and histomorphometric evaluations. Membranes harvested from 600 RCF produced significantly larger L-PRF clots (6.97g ± 0.95) in comparison to the lower 200 RCF (5.7g ± 0.95), with no significant differences between 600 and 400, and from 400 and 200 RCF. The three tested RCFs did not alter the platelet count of the L-PRF clot. For the in vivo component, quantitative bone regeneration analyses demonstrated significantly higher values obtained with L-PRF membranes extracted post 600 RCF (27.01 ± 8%) versus 200 RCF (17.54 ± 8%), with no significant differences regarding 400 RCF (~23 ± 8%). At the qualitative histological analyses, L-PRF membranes obtained at 600 and 400 RCFs yielded improved healing throughout the defect, where the L-PRF sourced from the lowest speed, 200 RCF, presented healing primarily at the margins along with the presence of connective tissue at the central aspect of the surgical defect. Higher 600 RCF yielded larger L-PRF clots/membranes, resulting in enhanced bone repair potential in association with PLGA scaffolds for the treatment of critical size bone defects.
PMID: 34080775
ISSN: 1552-4981
CID: 4905812
Histomorphometric analysis of implant osseointegration using hydrophilic implants in diabetic rats
OBJECTIVES/OBJECTIVE:To evaluate peri-implant bone formation of titanium implants using an in vivo rat model with and without uncontrolled diabetes mellitus (DM) to evaluate osseointegration of hydrophobic (Neoporos®) and hydrophilic (Acqua®) surfaces. MATERIALS AND METHODS/METHODS:54 rats were divided into two groups: DM group (DMG) (streptozotocin-induced diabetes) and a control group (CG). Implants with hydrophobic (Neoporos®) and hydrophilic surfaces (Acqua) were placed in the left or right tibia of animals. Animals were further divided into three groups (n = 9) euthanized after 7, 14, or 28 days. Bone-to-implant contact (BIC) and bone area fraction occupancy (BAFO) were assessed in total, cortical, and medullary areas. RESULTS:The DMG group, after a 7-day healing period, yielded with the Acqua implants presented significantly higher total BIC (+37.9%; p=0.03) and trabecular BIC (%) (+46.3%; p=0.02) values in comparison to the Neoporos implants. After 28 days of healing, the CG yielded that the cortical BAFO of Acqua implants to be significantly, 14%, higher (p=0.04) than Neoporos implants. CONCLUSION/CONCLUSIONS:The positive effects of the Acqua surface were able to counteract the adverse impact of uncontrolled DM at early osseointegration periods. After 28 days in vivo, the metabolic systemic impairment caused by DM overcame the surface treatment effect, leading to impaired osseointegration in both hydrophilic and hydrophobic implants. CLINICAL RELEVANCE/CONCLUSIONS:The adverse effects of diabetes mellitus with respect to bone healing may be minimized by deploying implants with strategically modified surfaces. This study evaluated the effects of implants with Acqua® and Neoporos® surfaces in both diabetic and healthy animals. During the initial healing period in diabetic animals, the hydrophilic surface was demonstrated to have beneficial effect on osseointegration in comparison to the hydrophobic surface. The results provide an insight into early healing, but the authors suggest that a future short-term and long-term clinical study is needed to assess the possible benefit of the Acqua® implant as well as in increasing the predictability of implant osseointegration.
PMID: 33765194
ISSN: 1436-3771
CID: 4894722
Comparative barrier membrane degradation over time: Pericardium versus dermal membranes
OBJECTIVE:The effectiveness of GBR procedures for the reconstruction of periodontal defects has been well documented. The objective of this investigation was to evaluate the degradation kinetics and biocompatibility of two resorbable collagen membranes in conjunction with a bovine xenograft material. MATERIALS AND METHODS/METHODS:Lower premolars and first molars were extracted from 18 male Yucatan minipigs. After 4 months of healing, standardized semi-saddle defects were created (12 mm × 8 mm × 8 mm [l˙̇ × W˙ × d]), with 10 mm between adjacent defects. The defects were filled with a bovine xenograft and covered with a either the bilayer collagen membrane (control) or the porcine pericardium-derived collagen membrane (test). Histological analysis was performed after 4, 8, and 12 weeks of healing and the amount of residual membrane evaluated. Non-inferiority was calculated using the Brunner-Langer mixed regression model. RESULTS:Histological analysis indicated the presence of residual membrane in both groups at all time points, with significant degradation noted in both groups at 12 weeks compared to 4 weeks (p = .017). No significant difference in ranked residual membrane scores between the control and test membranes was detected at any time point. CONCLUSIONS:The pericardium-derived membrane was shown to be statistically non-inferior to the control membrane with respect to resorption kinetics and barrier function when utilized for guided bone regeneration in semi-saddle defects in minipigs. Further evaluation is necessary in the clinical setting.
PMID: 33949796
ISSN: 2057-4347
CID: 4872312
Clinical application of a FOXO1 inhibitor improves connective tissue healing in a diabetic minipig model
The forkhead box O1 (FOXO1) transcription factor plays a key role in wound healing process. Recently it has been reported that lineage-specific genetic ablation of FOXO1 significantly improves diabetic wound healing in a mouse model. To investigate the clinical usefulness of these findings, translational preclinical studies with a large animal model are needed. We report for the first time that the local application of a FOXO1 inhibitor (AS1842856) significantly improves connective tissue healing in a preclinical T2DM minipig model, reflected by increased collagen matrix formation, increased myofibroblast numbers, improved angiogenesis, and a shift in cell populations from pro-inflammatory (IL-1β+, TNF-α+ and iNOS+) to pro-healing (CD163+). Our results set up the basis for the clinical application of a FOXO1 antagonist in early diabetic wounds where there is impaired connective tissue healing.
PMCID:7868841
PMID: 33594326
ISSN: 1943-8141
CID: 4820992
Comparison of Surface Treatments of Endosteal Implants in Ovariectomized Rabbits
PURPOSE/OBJECTIVE:The aim of this work was to evaluate osseointegration of endosteal implants with two different surface treatments at early stages (~3 weeks) in the tibia of healthy and ovariectomized rabbits. MATERIALS AND METHODS/METHODS:The study comprised 10 adult New Zealand female rabbits (Oryctolagus cuniculus; 6 months and 3.0 ± 0.5 kg). Five animals were subjected to bilateral ovariectomy to mimic osteoporotic-like conditions, and the remaining rabbits (n = 5) served as the healthy control group. After 3 months, specimens from the ovariectomized and control groups were subject to implant placement in both tibiae, using two different types of surface treatment. A total of 36 implants were placed, n = 18 acid-etched and n = 18 anodized. After 3 weeks, euthanasia of the animals was performed, and samples were obtained for processing. Bone-to-implant contact and bone area fraction occupancy were quantified to evaluate the osseointegration parameters around the implant surface and within the thread area, respectively, and nanoindentation tests were performed to determine elastic modulus and hardness of the new bone. Both analyses were performed on the entire implant (total), as well as individually within the cortical and bone marrow cavity area. RESULTS:All animals were evaluated with no signs of infection or postoperative complications. The total bone-to-implant contact and bone area fraction occupancy results, independent of surface treatment, yielded significant differences between the ovariectomized and control groups (P = .002 and P < .001, respectively). In the marrow cavity, analyzing the surface treatments independently as a function of bone condition, the only differences detected were in the anodized treatment (P = .04). Regarding the elastic modulus, differences were detected only with the anodized implants between the ovariectomized and control groups (P = .015). CONCLUSION/CONCLUSIONS:At 3 weeks after implant placement, there were better osseointegration values of the implants in the healthy control group compared with the ovariectomized group independent of surface treatment. Also, specifically in the medullary region of the rabbit tibia, the acid-etched implants had more uniform osseointegration values in conditions of low-quality bone in comparison to the anodized implants, histomorphometrically and biomechanically.
PMID: 33600521
ISSN: 1942-4434
CID: 4821002
Effect of Surgical Instrumentation Variables on the Osseointegration of Narrow- and Wide-Diameter Short Implants
PURPOSE/OBJECTIVE:The aim of the present study was to systematically analyze how a multifactorial surgical instrumentation approach affects osseointegration on both narrow-diameter and wide-diameter short implants. MATERIALS AND METHODS/METHODS:Twelve skeletally mature female sheep were used in the study along with 144 plateau-root-form healing chamber titanium (Ti-6Al-4V) implants (Bicon LLC, Boston, MA), evenly distributed between narrow (3.5 mm) and wide (6.0 mm) diameters. The presence or the absence of irrigation, different drilling speeds, and 2 time points quantifying bone-implant contact (BIC) and bone area fraction occupancy (BAFO) to evaluate the osteogenic parameters around the implants. RESULTS:There were no signs of inflammation, infection, or failure of the implants observed at either healing period. The narrow 3.5-mm implant, at 6 weeks, yielded significant differences in terms of BIC at a drilling speed of 50 rotations per minute (RPM), with higher values of the samples using irrigation (30.6 ± 6.1%) compared with those without (19.7 ± 6.1%). No statistical differences were detected for 500 and 1,000 RPM with or without irrigation. The wide 6-mm diameter implant showed differences with respect to drilling speed, 500 and 1,000 RPM, with higher values associated with samples subjected to irrigation. BAFO results, for both diameters, only detected statistical differences between the 2 times (3 vs 6 weeks); no statistical differences were detected when evaluating as a function of time, drilling speed, and irrigation. CONCLUSIONS:Surgical instrumentation variables (ie, drilling speed [RPM] and irrigation) yielded to be more of an effect for BIC at longer healing time (6 weeks) for the wider implants. Furthermore, deploying narrow or wide plateau-root-form implants, where conditions allow, has shown to be a safe alternative, considering the high BIC and BAFO values observed, independent of irrigation.
PMID: 33137302
ISSN: 1531-5053
CID: 4759432
Osseodensification drilling vs conventional manual instrumentation technique for posterior lumbar fixation: Ex-vivo mechanical and histomorphological analysis in an ovine model
Lumbar fusion is a procedure associated with several indications, but screw failure remains a major complication, with an incidence ranging 10% to 50%. Several solutions have been proposed, ranging from more efficient screw geometry to enhance bone quality, conversely, drilling instrumentation have not been thoroughly explored. The conventional instrumentation (regular [R]) techniques render the bony spicules excavated impractical, while additive techniques (osseodensification [OD]) compact them against the osteotomy walls and predispose them as nucleating surfaces/sites for new bone. This work presents a case-controlled split model for in vivo/ex vivo comparison of R vs OD osteotomy instrumentation in posterior lumbar fixation in an ovine model to determine feasibility and potential advantages of the OD drilling technique in terms of mechanical and histomorphology outcomes. Eight pedicle screws measuring 4.5 mm × 45 mm were installed in each lumbar spine of eight adult sheep (four per side). The left side underwent R instrumentation, while the right underwent OD drilling. The animals were killed at 6- and 12-week and the vertebrae removed. Pullout strength and non-decalcified histologic analysis were performed. Significant mechanical stability differences were observed between OD and R groups at 6- (387 N vs 292 N) and 12-week (312 N vs 212 N) time points. Morphometric analysis did not detect significant differences in bone area fraction occupancy between R and OD groups, while it is to note that OD showed increased presence of bone spiculae. Mechanical pullout testing demonstrated that OD drilling provided higher degrees of implant anchoring as a function of time, whereas a significant reduction was observed for the R group.
PMID: 32369220
ISSN: 1554-527x
CID: 4439042
3D printing of Microgel-loaded Modular LEGO-like Cages as Instructive Scaffolds for Tissue Engineering
ORIGINAL:0016709
ISSN: 2692-8205
CID: 5457512
Acknowledgement to reviewers of journal of functional biomaterials in 2019
SCOPUS:85083294074
ISSN: 2079-4983
CID: 5457232
Three-Dimensional Printing for Craniofacial Bone Tissue Engineering
The basic concepts from the fields of biology and engineering are integrated into tissue engineering to develop constructs for the repair of damaged and/or absent tissues, respectively. The field has grown substantially over the past two decades, with particular interest in bone tissue engineering (BTE). Clinically, there are circumstances in which the quantity of bone that is necessary to restore form and function either exceeds the patient's healing capacity or bone's intrinsic regenerative capabilities. Vascularized osseous or osteocutaneous free flaps are the standard of care with autologous bone remaining the gold standard, but is commonly associated with donor site morbidity, graft resorption, increased operating time, and cost. Regardless of the size of a craniofacial defect, from trauma, pathology, and osteonecrosis, surgeons and engineers involved with reconstruction need to consider the complex three-dimensional (3D) geometry of the defect and its relationship to local structures. Three-dimensional printing has garnered significant attention and presents opportunities to use craniofacial BTE as a technology that offers a personalized approach to bony reconstruction. Clinicians and engineers are able to work together to produce patient-specific space-maintaining scaffolds tailored to site-specific defects, which are osteogenic, osseoconductive, osseoinductive, encourage angiogenesis/vasculogenesis, and mechanically stable upon implantation to prevent immediate failure. In this work, we review biological and engineering principles important in applying 3D printing technology to BTE for craniofacial reconstruction as well as present recent translational advancements in 3D printed bioactive ceramic scaffold technology.
PMCID:7759279
PMID: 32842918
ISSN: 1937-335x
CID: 4751522
