Research

Biomaterials are widely used in dental applications, surgery, and drug delivery, and are critical for providing scaffolds for cell-mediated tissue repair. A group of investigators within the Center for Regenerative Medicine and Skeletal Development are engaged in Biomaterials research in the Center for Biomaterials. Major research areas include investigation of biomaterials important in dentistry and dental implants, use and design of scaffolds for engineering of bone and other tissue, novel materials including fiber composites, biomaterials for nano-particulate delivery and sustained release of anti-cancer drugs or osteogenic agents, catalyzed synthetic biomineralization and development of clinically-validated in vitro tests. Investigators are also exploring the utility of biomaterials for stem cell based regeneration and repair of skeletal tissue.

Extensive research is underway to elucidate the stages of progressive differentiation of bone, including identification and isolation of specific populations of osteoprogenitor cells yielding competent bone cells useful for bone regeneration. A unique tool being exploited in these studies is the use of genetic fluorescent markers of the bone cell lineage, which provides a means to evaluate lineage decisions during osteogenic differentiation in living tissue, and to FACS-isolate specific progenitor cell populations for evaluation of their suitability for repair of long bone fractures and critical-size skull defects.

Research in cartilage is investigating the genes and signals which control the initial differentiation of chondrocytes from limb mesenchymal cells, and their subsequent progressive maturation, during formation of the limb skeletal elements. Studies are also investigating the formation and specification of the joints which form between the limb cartilage elements, and the differentiation of the cartilage that comprises the joint surface. Investigators are also directing the differentiation of human stem cells into cartilage for the purpose of joint repair. These studies will help us to understand and ultimately treat, debilitating human conditions affecting the skeleton including chondrodysplasia and osteoarthritis.

Research is also underway to investigate the development and maintenance of skin, and the mechanisms of dermal wound healing, including the abnormal healing that occurs in the skin of patients with keloids in which excessive scar tissue forms in response to injury. Studies are in currently in progress to identify the genetic basis for human keloid formation.

The study of craniofacial and tooth development encompasses a broad area of research that investigates the control of cartilage, bone and tooth differentiation, as well as proper positioning and growth of the face, skull and teeth.

Research in Craniofacial and Tooth Development ongoing in the Center for Regenerative Medicine and Skeletal Development includes investigation of the role of transcription factors in epigenetic control of craniofacial and skeletal development, and in regulation of tooth cell development and differentiation. Studies are directing the differentiation of periodontal and dental pulp progenitor cells into osteoblasts and odontoblasts, potentially useful for craniofacial bone and tooth restoration, and stem cells are being used to model early differentiative events important for craniofacial morphogenesis. Investigators are also working to identify the genetic and molecular mechanisms responsible for the human congenital disorders craniometaphyseal dysplasia, cherubism, and Willimas-Bueren syndrome, which cause craniofacial abnormalities due to disruption of normal differentiation pathways.

Studies on vertebrate embryonic limb development have been conducted by a group of investigators within the Center for Regenerative Medicine and Skeletal Development in the context of an NIH Limb Program Project which has been continuously funded for nearly 20 years. These studies are investigating the molecular mechanisms that control limb formation and growth, including transcriptional control of limb patterning, growth factor signaling during initial limb specification and outgrowth, and the role of the extracellular matrix in limb patterning including specification of the limb skeletal elements and joints. Research is also investigating the involvement of signals and factors which are important in limb patterning in mediating embryonic limb regeneration.

Exciting potential exists for stem cell based therapies in the regeneration and repair of human bone or cartilage lost to injury, disease, or age. Cutting-edge research in the Center for Regenerative Medicine and Skeletal Development is already underway to evaluate the efficacy of various types of stem cells for skeletal tissue restoration, including adult bone marrow mesenchymal cells which contain subpopulations of osteogenic progenitors; pluripotent stem cells obtained from human embryos (hESC), and pluripotent stem cells derived from adult human fibroblasts (iPSC), which may be generated from the skin of the specific patient that needs repair.

A major award from the State of Connecticut Stem Cell Research Initiative has funded interdisciplinary and multidisciplinary research in stem cells being conducted by several members of the Center for Regenerative Medicine and Skeletal Development in the area of musculoskeletal tissue regeneration. This award is a Group Project Grant in which investigators are exploring directed differentiation of stem cells into the musculoskeletal lineage, including into bone and cartilage, as well as the design and use of biomaterial scaffolds for cell mediated repair, and the genomic analysis of skeletal progenitor populations. Specific stem cell related projects ongoing by Center members include isolation, evaluation and use of adult bone marrow derived stem cells for repair of long bone fractures and critical-size skull defects; directed differentiation of human stem cells into the cranial neural crest cell lineage for the purpose of regeneration of craniofacial tissue including teeth; utilization of fluorescent genetic markers of the musculoskeletal lineage to identify progenitor populations with unique regenerative capabilities; generation of biomaterials for delivery of stem cell based therapies; and directed differentiation of human stem cells into bone and cartilage for the purpose of bone and joint repair.

• For more about the State of Connecticut Group Project award to investigators in the Center for Regenerative Medicine and Skeletal Development for stem cell research, see the UConn Health Center magazine feature article: "Unlocking the Secrets of Embryonic Stem Cells" (PDF).
• For an update on the progress being made by investigators in the Center for Regenerative Medicine and Skeletal Development in the area of stem-cell based regeneration of cartilage for the purpose of joint repair, read the recent newspaper article in the Waterbury Republican: “UConn Researchers Take First Step Toward Arthritis Treatment.”