Biological studies



  1. Benitez BK, Brudnicki A, Surowiec Z, Singh RK, Nalabothu P, Schumann D, Mueller AA, Continuous Circular Closure in Unilateral Cleft Lip and Plate Repair in One Surgery, Journal of Cranio-Maxillofacial Surgery, 2021; 50(1).

    In this retrospective, descriptive cohort study wound healing and safety of single-stage two-layers continuous closure in patients with unilateral cleft lip and palate (UCLP) is assessed.
    Wound healing without fistula formation at 1, 3, and 6 months after a single-stage two-layer UCLP repair, in which the midline suture is continuously circular all along the oral and nasal sides is evaluated. We examined lengths of hospital stay and the incidence of intra- and postoperative adverse events. Furthermore, we compared the cleft width at birth and on the day of surgery, after presurgical orthopaedics. These preliminary results shows potential of the concept of single-stage continuous circular closure in UCLP for further investigation. In particular, it remains to be proven that there are no relevant adverse effects such as inhibition of maxillary growth. 

  2. Benitez B, Brudnicki A, Nalabothu P, von Jackowski J, Bruder E, Mueller AA. Histologic aspect of the curved vomerine mucosa in cleft lip and palate. The Cleft Palate-Craniofacial Journal 2021; Volume 59, Issue 8.

    Here, we report our histological analysis on the curved vomerin mucosa from 8 patients during surgical repair of cleft lip and palate at 8 months of age. The result from the mucoperiosteum overlying the curved vomer revealed characteristics consistent with those of an oral mucosa or a squamous metaplasia of the nasal mucosa. The vomer mucosa showed no specific signs of nasal mucosa. These findings can be considered in presurgical cleft orthopedics and palatal surgery for further refinement. Shifting the vomer mucosa according to important aspects of cleft repair such as primary healing and establishing optimal form and function of palatal roof and nasal floor should overrule a fixed physiologic belief commonly implemented in surgical techniques.
  3. Naudot M, Barre A, Caula A, Sevestre H, Dakpé S, Mueller AA, Devauchelle B, Testelin S, Marolleau JP, Le Ricousse S. Co-transplantation of Wharton’s jelly mesenchymal stem cell-derived osteoblasts with differentiated endothelial cells does not stimulate blood vessel and osteoid formation in nude mice models. J Tissue Eng Regen Med. 2019;14(2):257-271.

    A major challenge in bone tissue engineering is the lack of post-implantation vascular growth into biomaterials. In the skeletal system, blood vessel growth appears to be coupled to osteogenesis, suggestive of the existence of molecular crosstalk between endothelial cells (ECs) and osteoblastic cells. This study (performed in two murine ectopic models) aimed to determine whether co-transplantation of human Wharton's jelly mesenchymal stem cell-derived osteoblasts (WJMSC-OBs) and human differentiated ECs enhances bone regeneration and stimulates angiogenesis, relative to the seeding of WJMSC-OBs alone. In the two models, our cell-matrix environment combination did not seem to be optimal for inducing vascularized bone reconstruction.
    (Fondation des Gueules Cassées)
  4. Ducret M, Farges J-C, Pasdeloup M, Perrier-Groult E, Mueller AA, Mallein-Gerin F and Fabre H. Phenotypic Identification of Dental Pulp Mesenchymal Stem/Stromal Cells Subpopulations with Multiparametric Flow Cytometry. Odontogenes Methods Protoc Methods Mol Biol. 2019;1922(January):77-90.

    Dental pulp (DP) is a specialized, highly vascularized, and innervated connective tissue mainly composed of undifferentiated mesenchymal cells, fibroblasts, and highly differentiated dentin-forming odontoblasts. Precise identification of dental pulp mesenchymal stem cell (DP-MSC) population among the undifferentiated mesenchymal cells by surface antigens has proven difficult due lack of specificity. Multiparametric flow cytometry has been shown as a powerful tool, capable of detectiing several molecules on the surface of one single cell, to elucidate the phenotype of a cell population both in vivo and in vitro. The present paper describes the multiparametric flow cytometry protocol we routinely use for characterizing DP-MSCs including the design of the antibody panel and explains the selection of the different parameters related to the data quality control.

  5. Mueller AA, Forraz N, Gueven S, Degoul GAO, Pagnon-Minot A, Hartmann D, Martin I, Scherberich A, McGuckin C. Osteoblastic differentiation of wharton jelly biopsy specimens and their mesenchymal stromal cells after serum-free culturePlastic and Reconstructive Surgery. 2014; 134(1) 59e-69e. DOI: 10.1097/PRS.0000000000000305

    Cleft lip and cleft palate are increasingly being detected by prenatal ultrasound, which raises the opportunity of using the patient’s own osteogenicity from umbilical cord mesenchymal cells for bony repair. The growth of the cells under a fully defined and regulated protocol is presented. The osteogenic differentiation potential of Wharton jelly–derived mesenchymal stromal cells was maintained under serum-free isolation and expansion techniques. The cells without predifferentiation form a dense collagen matrix but not bone in vivo. Moreover, entire Wharton jelly biopsy specimens showed periosteal-like mineralization under osteogenic differentiation, which offers new options for autologous bone tissue engineering, including cleft palate surgery.
    (Margarete and Walter Lichtenstein foundation, Swiss National Science Foundation)

  6. Mueller, AA. Complementing surgical with biomedical and engineering methods to evolve lip and nose reconstruction. 2013, Doctoral Thesis, University of Basel, Faculty of Medicine.

  7. Mueller AA, Saldamli B, Stübinger S, Walter C, Flückiger U, Merlo A, Schwenzer-Zimmerer K, Zeilhofer HF and Zimmerer S. Oral bacterial cultures in nontraumatic brain abscesses: results of a first-line studyOral Surgery, Oral Med Oral Pathol Oral Radiol Endodontology. 2009;107(4):469-476.

    Bacterial cultures from nontraumatic brain abscesses (BAs) frequently contain oral bacteria. We assessed bacterial cultures from BAs and oral infective sources for a bacterial match. The findings of the study shows the importance of early collaboration among neurosurgeons, infectious disease specialists, and oral-maxillofacial surgeons in the identification and treatment of suspected oral sources of nontraumatic BAs.

  8. Brand S, Blechschmidt A, Mueller AA, Sader R, Schwenzer-Zimmerer K, Zeilhofer HF and Holsboer-Trachsler E. Psychosocial functioning and sleep patterns in children and adolescents with cleft lip and palate (CLP) compared with healthy controlsCleft Palate-Craniofacial J. 2009;46(2):124-135.

    This study aimed to assess psychological functioning, interactional competencies, and sleep patterns in children and adolescents with cleft lip and palate (CLP), and to compare these results with those from age- and gender-matched controls. It was hypothesized that participants with CLP would exhibit greater difficulties in psychological functioning, more interactional difficulties, and poorer sleep patterns than those without CLP. Participants with and without CLP did not differ with respect to emotional problems, conduct problems, hyperactivity or unfavorable sleep patterns. With respect to interactional competencies, participants with CLP in adolescence were more likely to report difficulties. Consequently, skill training to improve context-related social competencies may be appropriate.

  9. Leiggener CS, Curtis R, Mueller AA, Pfluger D, Gogolewski S, Rahn BA. Influence of copolymer composition of polylactide implants on cranial bone regenerationBiomaterials. 2006;27(2):202-207.

    Biodegradable polymers have become useful auxiliary materials for the functional and structural restoration of bone deficiencies. Commercial implants from poly(L /DL-lactide) 70:30 are used clinically for fracture fixation in regions of low load. Implants manufactured from poly(L /DL-lactide) 80:20 are currently being investigated experimentally. The present study addresses the hypothesis that early bone regeneration is not different for the two copolymers poly(L/DL -lactide) 70:30 and 80:20. In the early phase of bone regeneration the degradation process is still in its beginnings. Thus the copolymer composition has no effect on the amount or the morphology of the regenerate. Although the application of a hollow chamber design results in almost complete cranial defect filling, the end result can only be evaluated after the degradation process has been completed and full remodelling of the regenerate has been achieved. Long-term studies or accelerated degradation studies are required to confirm the expected advantages of poly(L /DL -lactide) 80:20.

  10. Mueller AA, Rahn BA, Gogolewski S, Leiggener CS. Early dural reaction to polylactide in cranial defects in rabbitsPediatr Neurosurg. 2005;41(6):285-291.

    Restoring the bone integrity to injured calvariae remains a challenge to surgeons. In this study, the dural biocompatibility of biodegradable poly-L/DL-lactide 80/20 and 70/30 defect covers, designed for guided bone regeneration, was assessed. For years, the amorphous poly-L/DL-lactide 70/30 has been used for commercial implants. After 8 weeks, the biocompatibility of both polylactides was equal showing only a few giant cells. The results obtained also provide some information about the reaction of intracranial biodegradable implants in pediatric craniofacial surgery.
    (Margarete and Walter Lichtenstein Foundation)