Biomaterials to Mimic and Heal Connective Tissues

Abstract

Connective tissue is one of the four major types of animal tissue and plays essential roles throughout the human body. Genetic factors, aging, and trauma all contribute to connective tissue dysfunction and motivate the need for strategies to promote healing and regeneration. The goal here is to link a fundamental understanding of connective tissues and their multiscale properties to better inform the design and translation of novel biomaterials to promote their regeneration. Major clinical problems in adipose tissue, cartilage, dermis, and tendon are discussed that inspire the need to replace native connective tissue with biomaterials. Then, multiscale structure-function relationships in native soft connective tissues that may be used to guide material design are detailed. Several biomaterials strategies to improve healing of these tissues that incorporate biologics and are biologic-free are reviewed. Finally, important guidance documents and standards (ASTM, FDA, and EMA) that are important to consider for translating new biomaterials into clinical practice are highligted.

Keywords: collagen; multiscale; regeneration; regulation; structure-function relations; therapeutics; translation.

Figure 1:. Anatomy and disease state affect connective tissue structure-function properties.

Adipose tissue, cartilage, dermis, and tendon are all examples of different types of connective tissues. In each panel group, the top panel depicts native tissue histology and the bottom panel depicts pathological conditions. Histological images were reproduced with permission.^[–100]

Figure 2:. Connective tissue and biomaterial assessment varies across length scales.

Methods to quantify material mechanics, structure, biology, and biochemistry vary when going from the whole organ (meter) to DNA (picometer) levels. The methods listed are representative examples for the different modes of analysis listed.

Figure 3:. Biomaterial strategies to mimic and heal connective tissues.

Several materials are engineered with varying structure and composition to recapitulate connective tissues, such as (a) adipose tissue, (b) cartilage, (c) dermis, and (d) tendon. In addition to using biologic-free approaches, methods incorporating cells, growth factors, and drugs are common.

Figure 4:. Guidance document recommendations vary between connective tissue type and agency.

Six guidelines for connective tissues were compared for 39 study descriptors and outcomes included. Although many guidelines contained similar standards, many were absent and not all guidelines for a given tissue were in agreement. Recommended guidelines do not imply adherence in basic science studies.