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Open Access Publications from the University of California

Scholarly Works (39 results)

  • Thesis
  • Peer Reviewed
UCLA Electronic Theses and Dissertations (2024)

Objective:  Hemifacial microsomia (HFM) is the second most common facial congenital anomaly. Distraction osteogenesis (DO) is one of the treatment modalities for patients with HFM and exhibits better post-op stability compared to other surgical modalities due to concurrent soft tissue expansion. Despite the increased popularity of DO, there is little research on its long-term outcome. Our objective was to evaluate changes in maxilla and mandible after distraction over twelve-year period.

Methods: Three HFM patients treated with DO were recalled at 9 time-points (T1-T9) over 12 years. The skeletal changes in chin position, maxillary width and height, occlusal height, and mandibular length were measured from posteroanterior cephalogram, 45° lateral oblique cephalograms, and cone-beam CT. Due to differences in traditional 2D radiographs (T1-T8) and 3D images from CBCT (T9), the ratio and angular measurements were used to evaluate the degree of asymmetry in addition to linear measurements. Effects on soft tissue were measured from photographs. Volume and surface analysis were proposed for future studies.

Results: Clinically significant improvements were seen after DO up to two-year post-DO (T7). Evaluations of the subsequent time-points revealed that with patient’s growth spurt, the skeletal growth of the affected, or experimental side lagged behind the unaffected, or control side, which served as control. The post-surgical recurrence of asymmetry was due to inherent growth potential difference rather than surgical relapse of DO. Twelve-year post-op (T9) showed that all patients had significant mandibular asymmetry compared to immediate post-op (T2). The degree of asymmetry at T9 was more severe than pre-op time-point (T1).

Conclusion: Even with overcorrection, due to the unpredictable and limited growth potential in the affected side, skeletal asymmetry worsened in HFM patient over 12 years post-DO.

    Cover page: Cephalometric Evaluation of Distraction Osteogenesis on Patients with Hemifacial Microsomia
    • Thesis
    • Peer Reviewed
    UCLA Electronic Theses and Dissertations (2012)

    Implant stability is an important factor guiding the selection of placement and loading protocols. An evaluation of the currently available techniques for measuring stability clearly demonstrates a need for a non-invasive, quantitative, repeatable, and reliable way to measure implant stability over time. A potential candidate for this purpose is resonance frequency analysis (RFA).

    A retrospective study was performed on implant patient data collected over a five-year period. Patients were categorized according to their placement protocol (one-stage vs. two-stage) and loading protocol (early vs. traditional). RFA measurements were recorded during placement and prior to loading. Survival or failure was determined after a minimum follow-up period of two years. Receiver operating characteristic (ROC) statistical analysis was used to determine ISQ cut-off points with respective sensitivity and specificity values for different placement and loading protocols.

    In predicting implant failure, sensitivity progressively increased and specificity decreased as ISQ cut-off values increased. All failures occurred at ISQ < 66 for the placement protocol and ISQ < 67 for the loading protocol. When ISQ values were less than 60, higher survival rates were observed when implants were placed utilizing a two-stage rather than a one-stage protocol. The area under the ROC curve for placement was 0.80 (p < 0.05) and the area under the ROC curve for loading was 0.89 (p < 0.05).

    RFA is a non-invasive technique used to measure the stability of implants and help guide placement and loading protocols. This study showed that increasing ISQ values correlated with increased sensitivity in detecting implant failure. Due to the high survival rates of dental implants, additional studies with an increased samples size and more implant failures are necessary to further elucidate the relationship between ISQ values and survival rates.

      Cover page: The Predictive Value of Resonance Frequency Analysis Measurements in the Surgical Placement and Loading of Endosseous Implants
      • Article
      • Peer Reviewed
      UCLA Previously Published Works (2017)
      In a quest to provide best-quality treatment, results, and long-term prognosis, physicians must be well versed in emerging sciences and discoveries to more favorably provide suitable options to patients. Bioengineering and regeneration have rapidly developed, and with them, the options afforded to surgeons are ever-expanding. Grafting techniques can be modified according to evolving knowledge. The basic principles of bioengineering are discussed in this article to provide a solid foundation for favorable treatment and a comprehensive understanding of the reasons why each particular treatment available can be the most adequate for each particular case.
        Cover page: Basic Principles of Bioengineering and Regeneration
        • Article
        • Peer Reviewed
        UCLA Previously Published Works (2017)

        Purpose

        Medication-related osteonecrosis of the jaws (MRONJ) is a well-described complication of antiresorptive and antiangiogenic medications. Although osteonecrosis can be associated with other inciting events and medications, such as trauma, infection, steroids, chemotherapy, and coagulation disorders, these are rarely reported in the literature.

        Materials and methods

        This is a six case series of MRONJ associated with medications other than antiresorptive or antiangiogenic drugs.

        Results

        Patient demographics, inciting event, location, stage, imaging findings, and outcome are reported.

        Conclusion

        With the continued development and clinical use of new biologic medications for diseases such as cancer and rheumatoid arthritis, it is important to continue to evaluate their effects on the oral cavity. The degree of risk for osteonecrosis in patients taking these new classes of drugs is uncertain but warrants awareness and monitoring.
          Cover page: Osteonecrosis of the Jaw in the Absence of Antiresorptive or Antiangiogenic Exposure: A Series of 6 Cases
          • Thesis
          • Peer Reviewed
          UCLA Electronic Theses and Dissertations (2012)

          Effects of Bone Morphogenetic Protein (rhBMP-2) and Platelet Derived Growth Factor (rhPDGF-BB) on Ectopic Bone Formation In Rats

          By

          Martin H. Mardirosian

          Master of Science in Oral Biology

          University of California, Los Angeles 2012

          Dr. Tara Aghaloo, Principal Investigator

          Dr. Sotirios Tetradis

          Dr. Peter K. Moy

          Dr. Flavia Pirih

          Marshall Urist first described a reproducible method by which to evaluate potentially osteoinductive molecules using a rat ectopic model to induce bone growth in vivo in non-bony, intramuscular sites.

          Recombinant human bone morphogenetic protein-2 (rhBMP-2) has been shown to induce de novo bone formation in ectopic implantations. When applied to an absorbable collagen sponge (ACS) carrier, the protein is retained at the site of implantation and induces bone formation in a non-bony site within two weeks in a subcutaneous rat ectopic model. The combination device of rhBMP-2/ACS has been approved by the FDA for use in anterior lumbar interbody fusions, acute, open tibial shaft fractures, and certain dental bone regenerative procedures.

          Recombinant human platelet-derived growth factor-BB (rhPDGF-BB) is approved for use in the treatment of certain periodontal defects when used in combination with a β-tricaclium phosphate (TCP) carrier. Thus far, no studies have demonstrated osteoinductive properties of PDGF.

          The purpose of this study was to compare the osteoinductivity of rhBMP-2 and rhPDGF-BB separately on both an ACS and carrier TCP when placed subcutaneously in rats.

          Thirty-two male immunocompetent 5 month old Sprague-Dawley rats were used in this study. Investigational materials were implanted subcutaneously in the rat thorax, with four randomized implants being placed per rat (e.g., one per quadrant). Animals received implantations of: rhBMP-2/ACS (0.3mg/mL), rhBMP-2/TCP (0.3mg/mL), rhPDGF-BB/TCP (0.3mg/mL), rhPDGF-BB/ACS (0.3mg/mL), ACS alone, or TCP alone. No animal received both rhBMP-2 and rhPDGF-BB. After sacrificing the animals after 2 and 4 weeks, quantitative and qualitative results were assessed using MicroCT and histology.

          rhBMP-2 showed considerable induction of bone growth at both 2 week and 4 week samples whether grown on TCP or ACS. MicroCT analysis revealed a significant increase in calcified tissue in rhBMP-2/ACS, rhBMP-2/TCP, and rhPDGF-BB/TCP in comparison to ACS alone control. However, only rhBMP-2/ACS at 2 and 4 weeks, not ACS alone nor rhPDGF-BB, was osteoinductive, as demonstrated by histology. H&E staining demonstrated immature woven bone at 2 weeks, which became more mature at the 4 week time point.rhPDGF-BB lacked the ability to induce bone formation, either with an ACS or TCP carrier .

          This study confirmed the osteoinductive properties of rhBMP-2/ACS and rhBMP-2/TCP, but failed to demonstrate that rhPDGF-BB is osteoinductive on either an ACS or TCP carrier. Due to its ability to induce de novo bone formation, rhBMP-2 is an important treatment option for patients with significant alveolar bone defects in the jaws, and will serve as a viable alternative to autogenous bone grafting.

            Cover page: Effects of Bone Morphogenetic Protein (rhBMP-2) and Platelet Derived Growth Factor (rhPDGF-BB) on Ectopic Bone Formation In Rats
            • Article
            • Peer Reviewed
            UCLA Previously Published Works (2015)
            Osteonecrosis of the jaw (ONJ) is a multifactorial disease in patients with primary or metastatic bone malignancy or osteoporosis undergoing systemic antiresorptive therapy, where pathophysiology has not yet been fully determined. The staging of ONJ is based on severity of symptoms and extent of clinical and radiographic findings. Treatment strategies range from conservative local wound care to aggressive resective surgery of all necrotic bone. The first ONJ cases were reported in 2003 and 2004, and although significant progress has been made in our understanding of the disease, much more work needs to be done to completely explain its pathophysiology.
              Cover page: Pathophysiology of Osteonecrosis of the Jaws
              • Article
              • Peer Reviewed
              UCLA Previously Published Works (2014)
              Osteonecrosis of the jaws (ONJ) is a complex disease involving multiple tissue and cell-type responses to wound healing or infection. AAOMS defines bisphosphonate related ONJ (BRONJ) as exposed, necrotic bone in the maxillofacial region that has persisted for more than 8 weeks in a patient with current or previous antiresorptive treatment, without a history of radiation therapy to the jaws. Since the first reported ONJ cases in 2003 and 2004, there has been little advancement in understanding the etiology and pathophysiology of ONJ. Many hypotheses have been proposed, including bisphosphonate (BP) toxicity to oral epithelium, altered wound healing after tooth extraction, high turnover of the mandible and maxilla, oral biofilm formation, infection and inflammation, and suppression of angiogenesis and bone turnover. The current classification system of ONJ involves stages 0 to 3 and is based on patient clinical presentation. This report describes a case of stage 0 ONJ in a patient on denosumab and indicates the full-spectrum similarities between BP- and denosumab-associated ONJ clinically, radiographically, and histologically.
                Cover page: Stage 0 Osteonecrosis of the Jaw in a Patient on Denosumab
                • Article
                • Peer Reviewed
                UCLA Previously Published Works (2019)
                Injectable hydrogels can fill irregular defects and promote in situ tissue regrowth and regeneration. The ability of directing stem cell differentiation in a three-dimensional microenvironment for bone regeneration remains a challenge. In this study, we successfully nanoengineer an interconnected microporous networked photocrosslinkable chitosan in situ-forming hydrogel by introducing two-dimensional nanoclay particles with intercalation chemistry. The presence of the nanosilicates increases the Young's modulus and stalls the degradation rate of the resulting hydrogels. We demonstrate that the reinforced hydrogels promote the proliferation as well as the attachment and induced the differentiation of encapsulated mesenchymal stem cells in vitro. Furthermore, we explore the effects of nanoengineered hydrogels in vivo with the critical-sized mouse calvarial defect model. Our results confirm that chitosan-montmorillonite hydrogels are able to recruit native cells and promote calvarial healing without delivery of additional therapeutic agents or stem cells, indicating their tissue engineering potential.
                  Cover page: Microporous methacrylated glycol chitosan-montmorillonite nanocomposite hydrogel for bone tissue engineeringCreative Commons 'BY' version 4.0 license
                  • Article
                  • Peer Reviewed
                  UCLA Previously Published Works (2018)

                  Purpose

                  Medication-related osteonecrosis of the jaws (MRONJ) is a known complication of antiresorptive medications with surgical and nonsurgical treatment options. The aim of this study was to evaluate the effectiveness of nonsurgical therapy using local wound care on management of MRONJ lesions.

                  Materials and methods

                  The authors conducted a retrospective cohort study of patients who presented to the University of California-Los Angeles School of Dentistry Oral and Maxillofacial Surgery Clinic for evaluation and treatment of MRONJ. The primary predictor variable was wound care score; secondary predictors were demographics (age, gender), anatomic location, primary condition, and type and time of antiresorptive treatment. Outcomes assessed were disease resolution and time to disease resolution. Statistical analysis was carried out using the Spearman correlation for continuous and ordinal variables or the χ2 test for categorical variables. Time-to-event statistics and Cox proportional hazards models were calculated; a Kaplan-Meier plot was generated to assess time to healing.

                  Results

                  One hundred six patients with 117 MRONJ lesions were treated using local wound care; complete disease resolution was observed 71% of lesions, with an additional 22% of lesions undergoing disease improvement. Wound care score was statistically associated with disease resolution and time to resolution, whereas demographics, anatomic site, condition, and type and time of antiresorptive treatment had no effect on resolution.

                  Conclusion

                  Local wound care increased the likelihood of MRONJ resolution and decreased the time to disease resolution. This strategy can be used in patients who cannot undergo surgery and should be implemented in all patients with MRONJ lesions who are managed nonsurgically.
                    Cover page: Nonsurgical Management of Medication-Related Osteonecrosis of the Jaws Using Local Wound Care
                    • Article
                    • Peer Reviewed
                    UCLA Previously Published Works (2019)

                    Purpose

                    Medication-related osteonecrosis of the jaw (MRONJ) is a rare but severe side effect of antiresorptive medications. Most animal models use tooth extraction as an instigating local factor to induce MRONJ, with varied results. However, these teeth are healthy and absent of dental disease, a rare finding that does not reflect clinical practices. The authors hypothesized that extraction of teeth with periapical inflammation would lead to MRONJ in rats treated with high-dose bisphosphonates.

                    Materials and methods

                    Rats were pretreated with zoledronic acid (ZA) for 1 week. Pulp exposure (PE) was established by exposing the pulpal chamber of the first and second molars. Experimental periapical disease (EPD) was induced by PE and bacterial inoculation into pulp chambers of the first and second mandibular molars. The mandibular molars were extracted 4 weeks after PE or EPD, and animals were euthanized 4 weeks after tooth extraction. Extraction sockets were assessed clinically, radiographically, and histologically.

                    Results

                    Clinically, radiographically, and histologically, socket healing was observed in all vehicle-treated animals and in ZA-treated animals after extraction of healthy teeth or teeth with PE. In contrast, bone exposure, lack of socket healing, and osteonecrosis were present in most ZA-treated animals after extraction of teeth with EPD. Bacterial presence was noted in areas of osteonecrotic alveolar bone.

                    Conclusion

                    These data support a synergistic contribution of severe dental disease and tooth extraction to MRONJ pathogenesis. Importantly, this model is amenable to manipulation of methodologic conditions for the dissection of parameters involved in MRONJ pathogenesis.
                      Cover page: Development of Medication-Related Osteonecrosis of the Jaw After Extraction of Teeth With Experimental Periapical Disease.
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