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Consultant: Dr. Yuehuei H. An

Human Long Bone Tissue Engineering

Bone loss is a major heath care problem worldwide and representing 10% of annual health care expenditures. Current treatments have been largely centered on replacing the lost bone with tissues of allogeneic or xenogeneic sources as well as synthetic bone substitutes, which in all lead to limited degree of structural and functional recovery. In addition, the use of allogeneic or xenogeneic tissue for bone repair involves risks of immune rejection, and disease transmission. Although autogenic bone grafts are commonly used and the most successful, they also have limitations such as additional surgery, donor site morbidity, and limited amount available. As a result, tissue engineering has emerged to regenerate the structures and therefore recover the functions of bone tissue rather than replacement alone. One decisive factor to the success of tissue engineering strategies for bone regeneration is the appropriate design of the scaffold. The design requirements for the scaffolds for bone tissue engineering may include biocompatibility, controlled degradability, mechanical integrity, vascularization inductivity, excellent bone guidance, osteoconductivity, and osteoinductivity. Due to the inability of currently available scaffolds to satiate all these requirements, the use of tissue engineering strategies in promoting bone regeneration hold promise although it has not been fully recognized. Current bone tissue engineering is limited to spongy bone engineering and there is lack of progress in compact bone engineering for human long bone repair. To this end, this study is aiming at engineering human long bone.

In an attempt to mimic the macro- and micro-structure of human long bone (Fig. 1A), we designed a novel biodegradable scaffold of a multi-channel (honeycomb) configuration consisting of unidirectional aligned selective permeable hollow fiber membranes (HFMs) of different sizes (Fig. 1B) which potentially has all the required properties mentioned above. A large HFM defines a controlled lumenal environment for bone tissue regeneration. A medium HFM that is concentrically entubulated into the large HFM encapsulates highly porous substrates for the spongy bone formation. Multiple small unidirectional aligned HFMs fill the space between the large and medium HFMs and mimic the osteon structures to guide compact bone regeneration. To further improve vascularization of the scaffold in vivo, pores of the sizes of small blood vessels (~50-100 m) will be created on the walls of the HFMs using laser micromachining facility. Our hypothesis is that a unidirectional aligned scaffold of honeycomb configuration (Fig. 1B) that closely mimic the natural bone structure and properties can induce highly directional bone tissue regeneration, leading to both structural and functional restoration to the levels similar to the natural bone tissue. The ultimate goal of this study is to produce highly efficacious scaffolds to engineer functional bone tissue with natural bone histological structure and properties for the cure of bone loss in clinical settings.

Fig. 1 (A). Schematic drawing of long bone microstructure (compact bone). (B-D) Schematic drawing of honeycomb scaffold for guided and biomimetic long bone tissue regeneration. (E) NanoHA-and degradable polymer based honeycomb scaffold. (F.) A honeycomb scaffold was implanted into radius defect rabbits to regenerate long bone.

A series of novel kneadable osteoconductive materials for orthopedic applications

1. New generation of bonewax:
Conventional beeswax-based bonewax may impair the ability of cancellous bone to clear bacteria. Also, it is not suitable for the use in infected areas where osseous regeneration and/or fusion is desired. In addition, it is non-degradable in the body and long-term foreign body reaction also causes many problems.
Our kneadable materials can be used as bonewax due to their kneadablity and thrombogenic properties. These materials are useful in stopping bleeding from damaged bone surfaces. Importantly, these materials may be used in infected areas, due to their ability in inhibiting growth of microorganisms if used alone or used combined with antibiotics. They may even prevent osteomyelitis. Their biodegradability eliminates the drawbacks of long-term foreign body reaction with beeswax-based bonewax. Their osteoconductivity, even osteoinductivity, allows our materials to be used for bone regeneration or bone fusion applications. Therefore, these materials can not only be used to control the bleeding from the bone, but also promote bone regeneration.

2. Irregular defect repair:
These materials are easy to shape into the shape of the defect by hand and also can be mixed with bioactive ceramics to form a scaffold with excellent osteoconductivity and osteoinductivity. Therefore, these materials can be used in spinal applications, such as postero-lateral fusion, cage filling material for interbody fusion, filling material for vertebral implants, and craniofacial applications, such as augmentation of alveolar bone for future tooth implants (These biocompatible putties can be inject directly without an incision on the gingiva.), and trauma and cranio-maxillofacial surgery.


Develop new biomaterials with osteoinductivity

We are also developing new biomaterials that promote osteogenesis as shown below.

Fig. 2. (A) X-ray photograph of bone formation on chemically modified chitosan; (B) X-ray photograph of bone formation on 50:50 ratio of chemically modified chitosan and PLGA. (C) X-ray photograph of bone formation on PLGA alone. (D) Extensive bone formation in chemically modified chitosan scaffolds.