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Novel cell sources for bone regeneration.

ABSTRACT: A plethora of both acute and chronic conditions, including traumatic, degenerative, malignant, or congenital disorders, commonly induce bone disorders often associated with severe persisting pain and limited mobility. Over 1 million surgical procedures involving bone excision, bone grafting, and fracture repair are performed each year in the U.S. alone, resulting in immense levels of public health challenges and corresponding financial burdens. Unfortunately, the innate self-healing capacity of bone is often inadequate for larger defects over a critical size. Moreover, as direct transplantation of committed osteoblasts is hindered by deficient cell availability, limited cell spreading, and poor survivability, an urgent need for novel cell sources for bone regeneration is concurrent. Thanks to the development in stem cell biology and cell reprogramming technology, many multipotent and pluripotent cells that manifest promising osteogenic potential are considered the regenerative remedy for bone defects. Considering these cells' investigation is still in its relative infancy, each of them offers their own particular challenges that must be conquered before the large-scale clinical application.

SUBMITTER: Li C

PROVIDER: S-EPMC8491221 | biostudies-literature | 2021 Jun

REPOSITORIES: biostudies-literature

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Novel cell sources for bone regeneration.

Li Chenshuang C Mills Zane Z Zheng Zhong Z

MedComm 20210504 2

A plethora of both acute and chronic conditions, including traumatic, degenerative, malignant, or congenital disorders, commonly induce bone disorders often associated with severe persisting pain and limited mobility. Over 1 million surgical procedures involving bone excision, bone grafting, and fracture repair are performed each year in the U.S. alone, resulting in immense levels of public health challenges and corresponding financial burdens. Unfortunately, the innate self-healing capacity of ...[more]

PMID: 34766140

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Project description:Mandibular osteoradionecrosis is a severe side effect of radiotherapy after the treatment of squamous cell carcinomas of the upper aerodigestive tract. As an alternative to its treatment by micro-anastomosed free-flaps, preclinical tissular engineering studies have been developed. Total bone marrow (TBM) associated with biphasic calcium phosphate (BCP) significantly enhanced bone formation in irradiated bone. One mechanism, explaining how bone marrow cells can help regenerate tissues like this, is the paracrine effect. The bone marrow cell extract (BMCE) makes use of this paracrine mechanism by keeping only the soluble factors such as growth factors and cytokines. It has provided significant results in repairing various tissues, but has not yet been studied in irradiated bone reconstruction. The purpose of this study was to evaluate the effect of BMCE via an intraosseous or intravenous delivery, with a calcium phosphate scaffold, in irradiated bone reconstruction. Twenty rats were irradiated on their hind limbs with a single 80-Gy dose. Three weeks later, surgery was performed to create osseous defects. The intraosseous group (n = 12) studied the effect of BMCE in situ, with six combinations (empty defect, BCP, TBM, BCP-TBM, lysate only, BCP-lysate). After four different combinations of implantation (empty defect, BCP, TBM, BCP-TBM), the intravenous group (n = 8) received four intravenous injections of BMCE for 2 weeks. Five weeks after implantation, samples were explanted for histological and scanning electron microscopy analysis. Lysate immunogenicity was studied with various mixed lymphocyte reactions. Intravenous injections of BMCE led to a significant new bone formation compared to the intraosseous group. The BCP-TBM mixture remained the most effective in the intraosseous group. However, intravenous injections were more effective, with TBM placed in the defect, with or without biomaterials. Histologically, highly cellularized bone marrow was observed in the defects after intravenous injections, and not after an in situ use of the lysate. The mixed lymphocyte reactions did not show any proliferation after 3, 5, or 7 days of lysate incubation with lymphocytes from another species. This study evaluated the role of BMCE in irradiated bone reconstruction. There were significant results arguing in favor of BMCE intravenous injections. This could open new perspectives to irradiated bone reconstruction.

Project description:Repair of critical sized bone defects, particularly in load-bearing areas, is a major clinical problem that requires surgical intervention and implantation of biological or engineered grafts. For load-bearing sites, it is essential to use engineered grafts that have both sufficient mechanical strength and appropriate pore properties to support bone repair and tissue regeneration. Unfortunately, the mechanical properties of such grafts are often compromised due to the creation of pores required to facilitate tissue ingrowth following implantation. To overcome the limitations associated with porous scaffolds and their reduced mechanical strength, we have developed a methodology for creating a solid structure that retains its bulk mechanical properties while also evolving into a porous structure in a biological environment through degradation and erosion. In this study, we utilized polyesters that have been approved by the FDA, including poly (lactic acid) (PLA), poly(glycolic acid) (PGA), their copolymer PLGA (PLGA, with a ratio of 85:15 and 50:50 of PLA:PGA), and poly(caprolactone) (PCL). These polymers and their ceramic composites with tricalcium phosphate (TCP) were compression molded into solid forms, which exhibited mechanical properties with compressive modulus as high as 2745 ± 364 MPa within the range of human trabecular bone and in the lower range of human cortical bone. The use of fast-degrading PLGA (50:50) and PGA as porogens allowed the formation of pores within the solid structures due to their degradation, and the TCP acts as a buffering agent to neutralize their acidic degradation byproducts. These scaffolds facilitated the growth of new blood vessels and tissue ingrowth in a subcutaneous implantation model. In addition, in a rat critical-sized mandibular bone defects these scaffolds supported bone growth with 70% of new bone volume fraction. Furthermore, the extent of bone regeneration was found to be higher for the scaffolds with bone morphogenic proteins (BMP2), indicating their suitability for bone repair and regeneration.

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Novel cell sources for bone regeneration.

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Novel cell sources for bone regeneration.

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