Optimizing bone wound healing using BMP2 with absorbable collagen sponge and Talymed nanofiber scaffold

Abstract

BackgroundBone is a highly vascularized and resilient organ with innate healing abilities, however some bone injuries overwhelm these attributes and require intervention, such as bone tissue engineering strategies. Combining biomaterials and growth factors, such as bone morphogenetic protein 2 (BMP2), is one of the most commonly used tissue engineering strategies. However, use of BMP2 has been correlated with negative clinical outcomes including aberrant inflammatory response, poor quality bone, and ectopic bone.MethodsIn the present study, a novel poly-n-acetyl glucosamine (pGlcNAc, trade name Talymed) scaffold was utilized in addition to the commonly used acellular collagen sponge (ACS) BMP2 delivery system in a murine calvarial defect model to investigate whether the innate properties of Talymed can reduce the noted negative bone phenotypes associated with BMP2 treatment.ResultsComparison of murine calvarial defect healing between ACS with and without Talymed revealed that there was no measurable healing benefit for the combined treatment. Healing was most effective utilizing the traditional acellular collagen sponge with a reduced dose of BMP2.ConclusionsThe results of this investigation lead to the conclusion that excessive dosing of BMP2 may be responsible for the negative clinical side effects observed with this bone tissue engineering strategy. Rather than augmenting the currently used ACS BMP2 bone wound healing strategy with an additional anti-inflammatory scaffold, reducing the dose of BMP2 used in the traditional delivery system results in optimal healing without the published negative side effects of BMP2 treatment.

Bone physiological microenvironment and healing mechanism: Basis for future bone-tissue engineering scaffolds

“…can enhance the mechanical properties and plasticity of the scaffold or biomimic the ECM inorganic components [ 240 ]. Note that collagen-based materials can also be used as a platform for the controlled release of biomolecules, such as cytokines [ 245 ], osteogenic agents [ 246 , 247 ] and miRNA [ 248 ]. An exhaustive introduction of the delivery of bioactive molecules is presented in Section 5 .…”

Sequential sequestrations increase the incorporation and retention of multiple growth factors in mineralized collagen scaffolds

“…Incorporating BMP2 into scaffolds for bone repair is very common and has shown to improve osteogenesis in multiple systems [36][37][38][39][40][41][42] . However, the need for doses of soluble BMP2 larger than what's normally found in the body has led to complications such as abnormal bone formation 43,44 .…”

3D printed scaffold combined to 2D osteoinductive coatings to repair a critical-size mandibular bone defect

“…James et al [17] reviewed the side effects of BMP-2 and noted that excessive concentrations of BMP-2 may be the most important factor contributing to the majority of adverse events: they noticed that increasing doses of BMP-2 do not necessarily result in higher fusion rates in spine procedures and long bone non-unions. These complications, described in clinical trials or in experimental studies, included postoperative inflammation (from benign seroma to life-threatening effects), ectopic bone formation, bone resorption and bone cyst formation, urogenital events (retrograde ejaculation, bladder retention) and wound complications [17,42,43]. The implication of BMP-2 in carcinogenesis is controversial.…”