Muscle engineering: guidance by the matrix

Sander Grefte

Cleft lip and/or palate repair requires the reconstruction of mucosa, muscle, and bone. In the cleft palate, the muscles of the soft palate are connected to the dorsal side of the palatal bone. During surgery, these muscles are detached and connected end-to-end to mimic the normal situation. However, optimal function is often not reached as fibrotic tissue is formed at the connection site. Satellite cells are the main cells responsible for muscle regeneration after injury but also for normal turnover of muscle cells. Upon injury these normally quiescent cells start to multiply, and form new muscle fibers while maintaining the satellite cell population. This property defines them as true stem cells though committed to a single lineage. The aim of this project is to develop scaffolds that guide (satellite) stem cells into regenerating a functional muscle while maintaining a reservoir of satellite cells. This will be pursued by culturing isolated satellite cells and bone marrow stem cells on specifically designed scaffolds. In vivo, normal muscle regeneration will be studied after experimental injury of the soleus muscle of rats. Finally, constructs will be implanted into the defect to improve regeneration. The techniques developed in this project will facilitate further studies on the muscles of the soft palate.

Regulatory factors in palatogenesis and cleft palate

Liuyan Meng

Cleft palate is caused by a failure of the embryonic fusion of the paired palatal shelves. Both genetic and environmental factors contribute to the etiology of cleft palate. We have found differences in the expression of several regulatory factors such as one of the wnt proteins, by palatal fibroblasts from patients and age-matched controls. In this project, differences in protein expression, and in functional characteristics of these palatal fibroblasts are further analyzed in in vitro cell culture models. In addition, the expression of these proteins is investigated in normal mouse palatogenesis by immunohistochemistry and quantitative PCR. The role of these proteins is analyzed using an in vitro model for palatal fusion with isolated mouse embryonic palatal shelves. The effects of specific signaling proteins or signaling inhibitors on palatal fusion are analyzed. This study will clarify the biological mechanisms in palatogenesis and cleft palate, which may offer new strategies for cleft prevention.

From stem cells to myofibroblasts

Jochem Verstappen

Healing of open wounds involves wound contraction and scar formation. These generally beneficial processes are a main cause of functional and/or growth impairment in specific situations such as burn wounds around the joints, or the healing of surgical wounds after cleft palate repair. In the latter situation, scar formation on the palate impairs normal growth of the upper jaw, which requires additional orthodontic or surgical treatment. Myofibroblasts mediate wound contraction and subsequent scarring. The present study has two major aims;

• To unravel the development of wound myofibroblasts from circulating precursor cells in vivo.
• To develop new strategies to prevent wound-induced growth impairment by modulating cell-matrix interactions that lead to contraction and scarring.

Poster wetenschapssdag 2007

Tissue engineering for cleft palate repair

Ricardo Ophof

Lack of palatal tissue is an important technical problem in the surgical closure of a cleft palate leading to areas of bare bone that are left for secondary epithelialization. This procedure induces the formation of extensive scar tissue. As a result, the growth of the maxilla and the development of the dentition are disturbed. New developments within the field of tissue engineering allow the construction of skin and mucosal substitutes containing cultured cells and artificial matrices. The aim of this study is to develop a substitute for oral mucosa using keratinocytes from the dog. The substitutes are evaluated in a simulated cleft palate repair in the dog. More info….

Improvement of palatal wound healing with growth factor-loaded collagen matrices

Richard Jansen

The surgical treatment of patients with a cleft palate is complicated by a shortage of mucosal tissue on the palate. Large open wounds exposing the palatal bone remain after surgery. In these areas wound contraction occurs and extensive scar tissue is formed which is firmly attached to the palatal bone. These processes are major factors in the impairment of growth and development of the dento-maxillary complex that occurs after closure of the palatal cleft. In the present project we will use collagen matrices to deliver growth factors in an existing wound model in rats. The aim of this research project is to prevent growth impairment by reducing the wound contraction and limiting the formation of scar tissue on the palate.
more info..

Poster EOS 2005 Richard Jansen

Craniofacial adaptation to mechanical factors

Mette Kuijpers

Orthodontic treatment influences the growth and development of craniofacial structures. Next to the teeth, also soft tissues, muscles, and bone adapt to treatment. This also happens during growth, and the adaptation to changes in food hardness. This study investigates the mechanisms of adaptation of craniofacial structures to mechanical loading. It is mainly focussed on the masseter muscles, facial sutures and the periodontal ligament.