Bony defects in the craniomaxillofacial skeleton remain a major and challenging health concern. Surgeons have been trying for centuries to restore functionality and aesthetic appearance using autografts, allografts, and even xenografts without entirely satisfactory results. As a result, physicians, scientists, and engineers have been trying for the past few decades to develop new techniques to improve bone growth and bone healing. In this review, the authors summarize the advantages and limitations of current animal models; describe current materials used as scaffolds, cell-based, and protein-based therapies; and lastly highlight areas for future investigation. The purpose of this review is to highlight the major scaffold-, cell-, and protein-based preclinical tools that are currently being developed to repair cranial defects.
Bone repair and regeneration is a dynamic process that involves a complex interplay between the (1) ground substance, (2) cells, and (3) milieu. While each constituent is integral to the final product, it is often helpful to consider each component individually. Therefore, we created a two-part review to examine scaffolds and cells' roles in bone tissue engineering. In Part I, we review the myriad of materials use for in vivo bone engineering. In Part II, we discuss the variety cell types (e.g., osteocytes, osteoblasts, osteoclasts, chondrocytes, mesenchymal stem cells, and vasculogenic cells) that are seeded upon or recruited to these scaffolds. In Part III, we discuss the optimization of the microenvironment. The biochemical processes and sequence of events that guide matrix production, cellular activation, and ossification are vital to developing successful bone tissue engineering strategies and are thus succinctly reviewed herein.
There is tremendous interest in autologous fat grafting for the management of soft tissue volume deficiencies, treatment of cutaneous injuries, and regeneration of missing parts. Given its relative abundance and proximity to the surface of the skin, adipose tissue seems an excellent choice for the treatment of both congenital and acquired soft tissue defects, but the mesenchymal stem cells contained within the fat may provide unexpected opportunities for tissue replacement and repair. Although adipose transfer has been successfully used for reconstructive purposes since the end of the 19th century, numerous controversies about adipose harvesting, processing, delivery, survival, and efficacy still persist today. The purpose of this article was to highlight current practices, areas of controversy, and near-term future applications of fat grafting for reconstruction of the face.
Background
Prolyl hydroxylase domain 2 (PHD2) has been implicated in several pathways of cell signaling, most notably in its regulation of hypoxia inducible factor (HIF)-1α stability. In normoxia, PHD2 hydroxylates proline residues on HIF-1α, rendering it inactive. However in hypoxia, PHD2 is inactive, HIF-1α is stabilized and downstream effectors such as VEGF and FGF-2 are produced to promote angiogenesis. In the present study we utilize RNAi to PHD2 to promote therapeutic angiogenesis in a diabetic wound model, presumably by the stabilization of HIF-1α.
Methods
Stented wounds were created on the dorsum of diabetic Lpr db/db mice. Mice were treated with PHD2 siRNA or nonsense siRNA. Wounds were measured photometrically on days 0–28. Wounds were harvested for histology, protein, and RNA analysis.
Results
Diabetic wounds treated with siRNA closed within 21 +/−1.2 days; sham treated closed in 28 +/−1.5 days. By day 7, Western blot revealed near complete suppression of PHD protein and corresponding increased HIF-1α. Angiogenic mediators VEGF and FGF-2 were elevated, corresponding to increased CD31 staining in the treated groups.
Conclusions
siRNA-mediated silencing of PHD2 increases HIF-1α and several mediators of angiogenesis. This corresponded to improved time to closure in diabetic wounds compared to sham treated wounds. These findings suggest that impaired wound healing in diabetes can be ameliorated with therapeutic angiogenesis.
Adding HHR to LAGB where indicated significantly reduces reoperation rate. Every effort should be made to detect and repair HHR during placement of the band, as it will decrease future need for reoperation.
It appears there is an acceleration of early phase (day 7 to day 21) dermal incorporation with fibrin glue application to the wound bed, perhaps secondary to increased cellular migration. Day 21 appears to be too early to apply cultured keratinocytes either as sheets or aerosolized suspension.
The present article reports on the successful management of a large flail chest with traumatic pulmonary herniation in a patient who could not be weaned from mechanical ventilation following a course of conservative management. Surgical intervention involved open reduction and internal fixation with tubular plates to stabilize the flail segment, followed by a pectoralis major myocutaneous flap to repair the chest wall defect. Following surgical intervention, the patient was able to be weaned from mechanical ventilation and showed remarkable improvement in pulmonary function parameters. To the authors’ knowledge, the present report is the first to describe the use of open reduction and internal fixation of the chest wall and flap reconstruction to treat lung herniation with a flail chest segment.
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