Wade Nedderman

Introduction: Bone disorders have trended upwards recently, especially in populations plagued by obesity and the aging baby boomer population¹. Autografts are the current gold standard for bone replacement as a result of its histocompatibility and non-immunogenic properties¹. Autografts do have limitations though, including donor site deformity and potentially lack of required donor volume for larger bone deficits². Bone tissue engineering could provide a more effective means of treatment for bone deformities by reducing donor site morbidity and increasing the supply of feasible bone available³. The challenge of bone tissue engineering is lack of adequate vascularization⁴. This paper will focus on discussing two techniques used to improve angiogenesis in bone tissue engineering, co-cultures and in situ tissue engineering. Successfully implementation of these techniques will greatly improve the prognosis of large bone deficits that would have been untreatable due to size constrictions and reduce donor site morbidity of autografts⁵. Methods: The co-culture was created by culturing human mesenchymal stem cells (hMSCs) with human umbilical vein endothelial cells (HUVECs) and folding it three times, creating an eight layered construct. The construct was implanted into a mouse and density of blood vessels was measured at 7 and 14 days’ post implantation via H&E staining. In situ tissue engineering is achieved by creating a 3D tissue construct seeded with hMSCs⁶. Vascularization is achieved by using an arteriovenous (AV) loop created by a vein graft. The construct was then implanted into a patient. The patient was followed up at 14 and 32 months with a CT and MRI, evaluating the integrity of the AV loop and extent of bone repair⁷.  Results: The co-culture had a statistically significantly increase in blood vessel formation 7 and 14 days’ post-implantation, compared to the control, hMSCs constructs without HUVECs⁵. The patient who underwent in situ tissue engineering showed a patent AV loop at the 14 and 32 month follow up appointment as well as complete bone repair.  Discussion: Angiogenesis is a major obstacle in tissue engineering. Two possible solutions are co-cultures and in situ tissue engineering. Co-cultures have yet to be tested clinically, but in a mouse model have shown improved angiogenesis in vivo. In situ tissue engineering has already shown clinical success and provides yet another mechanism to vascularize constructs.

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