Bone tissue engineering in oral peri-implant defects in preclinicalin vivoresearch: A systematic review and meta-analysis

Abstract

The regeneration and establishment of osseointegration within oral peri-implant bone defects remains a clinical challenge. Bone tissue engineering (BTE) is emerging as a promising alternative to autogenous and/or biomaterial-based bone grafting. The objective of this systematic review was to answer the focused question: in animal models, do cell-based BTE strategies enhance bone regeneration and/or implant osseointegration in experimental peri-implant defects, compared with grafting with autogenous bone or only biomaterial scaffolds? Electronic databases were searched for controlled animal studies reporting on peri-implant defects and implantation of mesenchymal stem cells (MSC) or other cells seeded on biomaterial scaffolds, following Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) guidelines. Random effects meta-analyses were performed for the outcomes histomorphometric bone area fraction (BA) and bone-to-implant contact (BIC). Nineteen studies reporting on large animal models (dogs and sheep) were included. Experimental defects were created surgically (16 studies) or via ligature-induced peri-implantitis (LIPI, three studies). In general, studies presented with an unclear to high risk of bias. In most studies, MSC were used in combination with alloplastic mineral phase or polymer scaffolds; no study directly compared cell-loaded scaffolds vs. autogenous bone. In three studies, cells were also modified by ex vivo gene transfer of osteoinductive factors. The meta-analyses indicated statistically significant benefits in favour of: (a) cell-loaded vs. cell-free scaffolds [weighted mean differences (WMD) of 10.73-12.30% BA and 11.77-15.15% BIC] in canine surgical defect and LIPI models; and (b) gene-modified vs. unmodified cells (WMD of 29.44% BA and 16.50% BIC) in canine LIPI models. Overall, heterogeneity in the meta-analyses was high (I 70-88%); considerable variation was observed among studies regarding the nature of cells and scaffolds used. In summary, bone regeneration and osseointegration in peri-implant defects are enhanced by the addition of osteogenic cells to biomaterial scaffolds. Although the direction of treatment outcome is clearly in favour of BTE strategies, due to the limited magnitude of treatment effect observed, no conclusive statements regarding the clinical benefit of such procedures for oral indications can yet be made. Copyright © 2017 John Wiley & Sons, Ltd.

The adjunctive effect of rhBMP‐2 on the regeneration of peri‐implant bone defects after experimental peri‐implantitis

“…The addition of bioactive agents and growth factors has been proposed to enhance the bone regenerative outcomes. In fact, the addition of bone morphogenetic proteins (BMPs) has shown promising results when combined with guided bone regeneration, in terms of promoting additional bone formation when compared with the scaffold alone (Jung, Thoma, & Hammerle, 2008;Kelly, Vaughn, & Anderson, 2016;Shanbhag, Pandis, Mustafa, Nyengaard, & Stavropoulos, 2018). When this principle has been applied to the treatment of experimental peri-implantitis, two studies have assessed the added benefit of adding rhBMP-2 to a vehicle carrier.…”

Cell therapy for orofacial bone regeneration: A systematic review and meta‐analysis

“…Uncontrolled studies (UT) and cases reports (with ≥3 patients) of cell‐based BTE were also identified to capture possible relevant information regarding cell sources, delivery strategies, and adverse events, although data regarding bone regeneration from these studies were not considered for the meta‐analyses. Sampling of pre‐clinical data was limited to large‐animal models and regards mainly an update of our previously published reviews (Shanbhag et al., , ). These data were only included to compare with the clinical data, which is the focus of the present review.…”

“…The cells can be harvested by minimally, and relatively less, invasive techniques (compared to AB harvesting) from various tissues, most commonly bone marrow and adipose tissues, under local anaesthesia, and without the need for hospitalization. Thus, BTE strategies are indeed emerging as promising alternatives to AB and/or biomaterial‐based grafting, as demonstrated by several pre‐clinical and some clinical studies (for reviews, see Janssen et al., ; Padial‐Molina et al., ; Shanbhag et al., 2015; Shanbhag, Pandis, Mustafa, Nyengaard, & Stavropoulos, , ; Miguita, Mantesso, Pannuti, & Deboni, ). Among these BTE strategies, three main interventions using cell therapies have been tested: (a) use of “minimally manipulated” whole tissue fractions; (b) use of more‐than‐minimally manipulated or ex vivo expanded uncommitted stem/progenitor cells; and (c) use of ex vivo expanded committed bone‐derived cells.…”

The Use of Pulsed Electromagnetic Fields to Promote Bone Responses to Biomaterials In Vitro and In Vivo

“…Biomaterials play an important role in bone regenerative strategies [ 1 ] in both orthopedics and dentistry as scaffolds [ 2 ] or as a support for prosthesis, e.g., hip or dental implants [ 3 ]. In all these clinical situations the challenge biomaterials must face is to integrate in the host and promote bone healing along its surfaces [ 4 ], albeit with noticeable differences.…”